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Brandi N, Renzulli M. Liver Lesions at Risk of Transformation into Hepatocellular Carcinoma in Cirrhotic Patients: Hepatobiliary Phase Hypointense Nodules without Arterial Phase Hyperenhancement. J Clin Transl Hepatol 2024; 12:100-112. [PMID: 38250460 PMCID: PMC10794268 DOI: 10.14218/jcth.2023.00130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 07/04/2023] [Accepted: 07/25/2023] [Indexed: 01/23/2024] Open
Abstract
Recent technical advances in liver imaging and surveillance for patients at high risk for developing hepatocellular carcinoma (HCC) have led to an increase in the detection of borderline hepatic nodules in the gray area of multistep carcinogenesis, particularly in those that are hypointense at the hepatobiliary phase (HBP) and do not show arterial phase hyperenhancement. Given their potential to transform and advance into hypervascular HCC, these nodules have progressively attracted the interest of the scientific community. To date, however, no shared guidelines have been established for the decision management of these borderline hepatic nodules. It is therefore extremely important to identify features that indicate the malignant potential of these nodules and the likelihood of vascularization. In fact, a more complete knowledge of their history and evolution would allow outlining shared guidelines for their clinical-surgical management, to implement early treatment programs and decide between a preventive curative treatment or a watchful follow-up. This review aims to summarize the current knowledge on hepatic borderline nodules, particularly focusing on those imaging features which are hypothetically correlated with their malignant evolution, and to discuss current guidelines and ongoing management in clinical practice.
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Affiliation(s)
- Nicolò Brandi
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Matteo Renzulli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
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A Pre-TACE Radiomics Model to Predict HCC Progression and Recurrence in Liver Transplantation. A Pilot Study on a Novel Biomarker. Transplantation 2021; 105:2435-2444. [PMID: 33982917 DOI: 10.1097/tp.0000000000003605] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
BACKGROUND Despite Trans-Arterial Chemo Embolization (TACE) for hepatocellular carcinoma (HCC), a significant number of patients will develop progression on the liver transplant (LT) waiting list or disease recurrence post-LT. We sought to evaluate the feasibility of a pre-TACE radiomic model, an imaging-based tool to predict these adverse outcomes. METHODS We analyzed the pre-TACE computed tomography images of patients waiting for a LT. The primary endpoint was a combined event that included waitlist dropout for tumor progression or tumor recurrence post-LT. The radiomic features were extracted from the largest HCC volume from the arterial and portal venous phase. A third set of features was created, combining the features from these 2 contrast phases. We applied a LASSO feature selection method and a support vector machine classifier. Three prognostic models were built using each feature set. The models' performance was compared using 5-fold cross-validated Area Under the Receiver Operating Characteristic curves (AUC). RESULTS 88 patients were included, of whom 33 experienced the combined event (37.5%). The median time to dropout was 5.6 months (IQR:3.6-9.3), and the median time for post-LT recurrence was 19.2 months (IQR:6.1-34.0). Twenty-four patients (27.3%) dropped out, and 64 (72.7%) patients were transplanted. Of these, 14 (21.9%) had recurrence post-LT. Model performance yielded a mean AUC of 0.70(±0.07), 0.87(±0.06) and 0.81(±0.06) for the arterial, venous and the combined models, respectively. CONCLUSION A pre-TACE radiomics model for HCC patients undergoing LT may be a useful tool for outcome prediction. Further external model validation with a larger sample size is required.
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Abstract
As opposed to most solid cancers, hepatocellular carcinoma (HCC) does not necessarily require histological confirmation. Noninvasive diagnosis is possible and relies on imaging. In cirrhotic patients, the diagnosis can be obtained in tumors displaying typical features that include non-rim arterial phase hyperenhancement followed by washout during the portal venous and/or delayed phases on CT or MR imaging. This pattern is very specific and, as such, has been endorsed by both Western and Asian diagnostic guidelines and systems. However, its sensitivity is not very high, especially for small lesions. Numerous ancillary features favoring the diagnosis of HCC may be depicted, including appearance after injection of hepatobiliary MR imaging contrast agents. These features increase confidence in diagnosis, but cannot be used as substitutes to liver biopsy. Aside from its diagnostic purpose, imaging also helps to assess tumor biology and patient outcome, by identifying features of local invasiveness. The purpose of this review article is to offer an overview of the role of imaging for the diagnosis and prognostication of HCC.
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Peng Z, Li C, Chan T, Cai H, Luo Y, Dong Z, Li ZP, Feng ST. Quantitative evaluation of Gd-EOB-DTPA uptake in focal liver lesions by using T1 mapping: differences between hepatocellular carcinoma, hepatic focal nodular hyperplasia and cavernous hemangioma. Oncotarget 2017; 8:65435-65444. [PMID: 29029443 PMCID: PMC5630343 DOI: 10.18632/oncotarget.18918] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2016] [Accepted: 06/14/2017] [Indexed: 12/22/2022] Open
Abstract
Objectives To investigate the difference of T1 relaxation time on Gd-EOB-DTPA-enhanced MRI in hepatocellular carcinoma (HCC), hepatic focal nodular hyperplasia (FNH) and cavernous hemangioma of liver (CHL), and to quantitatively evaluate the uptake of Gd-EOB-DTPA in these three focal liver lesions (FLLs). Results The T1P of CHL was significantly higher than those of HCC and FNH (P < 0.05). Reduction of T1 relaxation time on hepatobiliary phase could be observed in all three types of lesions. There were significant differences of T1P, T1E, T1D and T1D% between FNH, CHL and HCC (P < 0.001). Spearman correlation analysis revealed that T1D% was the best indicator for diagnostic differentiation, with a correlation coefficient of 0.702. Discriminant analysis using three variables (T1P, T1E, and T1D%) showed that the classification accuracy was 88.2%. Materials and Methods 74 patients diagnosed with focal liver lesions underwent Gd-EOB-DTPA-enhanced MRI including T1 mapping were enrolled, consisting of 51 HCCs, 10 FNHs, and 13 CHLs. T1 relaxation times of these lesions were measured on pre-contrast (T1P) and on hepatobiliary phase images at 20 minute after contrast (T1E). The reduction of T1 relaxation time on hepatobiliary (T1D) and the percentage reduction (T1D%) was calculated. The differences of T1P, T1E, T1D and T1D% in these FLLs were analyzed. The usefulness of these parameters for classification of FLLs was evaluated. Conclusions Uptake of Gd-EOB-DTPA is different between in HCC, FNH and CHL. These three lesions can be distinguished using T1 mapping.
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Affiliation(s)
- Zhenpeng Peng
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong, China
| | - Chang Li
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong, China
| | - Tao Chan
- Department of Diagnostic Radiology, The University of Hong Kong, Pokfulam, Hong Kong
| | - Huasong Cai
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong, China
| | - Yanji Luo
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong, China
| | - Zhi Dong
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong, China
| | - Zi-Ping Li
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong, China
| | - Shi-Ting Feng
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong, China
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Diagnostic efficacy of the Liver Imaging-Reporting and Data System (LI-RADS) with CT imaging in categorising small nodules (10-20 mm) detected in the cirrhotic liver at screening ultrasound. Clin Radiol 2017; 72:901.e1-901.e11. [PMID: 28673446 DOI: 10.1016/j.crad.2017.05.019] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Revised: 05/23/2017] [Accepted: 05/26/2017] [Indexed: 11/24/2022]
Abstract
AIM To estimate the diagnostic accuracy of the Liver Imaging-Reporting and Data System (LI-RADS) with computed tomography (CT) for diagnosing hepatic nodules (10-20 mm) detected in cirrhotic livers. MATERIALS AND METHODS Fifty-five patients with liver cirrhosis and a solitary nodule (10-20 mm in diameter) detected via ultrasound surveillance, underwent hepatic CT and fine-needle biopsy. All the CT images were analysed and the lesions were categorised into five categories according to the LI-RADS. RESULTS Final diagnoses of the 55 nodules were as follows: 34 hepatocellular carcinomas (HCCs), one intrahepatic cholangiocarcinomas, one adrenocortical carcinoma metastasis, and 19 benign lesions. None (0%) of four LI-RADS category 1 lesions, two (22%) of nine category 2 lesions, seven (50%) of 14 category 3 lesions, two (67%) of three category 4 lesions, 22 (96%) of 23 category 5 lesions and one (50%) of two lesions classified as other malignancies was HCC. One category 5 lesion was adrenocortical carcinoma metastasis and one of two lesions categorised as other malignancies was intrahepatic cholangiocarcinoma. In patients with nodules detected at surveillance ultrasound, the best threshold for confident HCC diagnosis was more than LI-RADS category 3. The use of this threshold produced a sensitivity and specificity of 72.7% and 90%, respectively. So combining LI-RADS 4 and 5 categories for confident HCC diagnosis would improve accuracy and sensitivity with no significant impairment of specificity or positive predictive value. CONCLUSION LIRADS with CT provides a strong validity for the diagnosis of small hepatic nodules, and is very useful to improve the accuracy of CT reports.
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Tong HF, Liang HB, Mo ZK, Guan TP, Yang J, Fang CH. Quantitative analysis of gadoxetic acid-enhanced magnetic resonance imaging predicts histological grade of hepatocellular carcinoma. Clin Imaging 2017; 43:9-14. [PMID: 28153667 DOI: 10.1016/j.clinimag.2016.12.009] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2016] [Revised: 12/15/2016] [Accepted: 12/19/2016] [Indexed: 12/13/2022]
Abstract
OBJECTIVE To confirm the histological grade of hepatocellular carcinoma (HCC) by gadoxetic acid-enhanced MRI. METHODS Ninety-five HCC patients underwent gadoxetic acid-enhanced MRI before surgical intervention. The correlations among the signal absolute enhancement, contrast enhancement ratio (CER) and tumor histological grade were analyzed. RESULTS The correlation between CER of tumor-to-liver and the grades of tumor differentiation is the most significant negative. The k-value for the CER of tumor-to-liver and histopathologic analysis is 0.62, which gives evidence of good agreement. CONCLUSION The quantitative analysis of gadoxetic acid-enhanced MRI can predict the histological grades of small HCCs.
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Affiliation(s)
- Hong-Fei Tong
- Department of Hepatobiliary Surgery, ZhuJiang Hospital of Southern Medical University, Guangzhou, Guangdong Province 510282, China.
| | - Hong-Bo Liang
- Department of Hepatobiliary Surgery, ZhuJiang Hospital of Southern Medical University, Guangzhou, Guangdong Province 510282, China
| | - Zhi-Kang Mo
- Department of Hepatobiliary Surgery, ZhuJiang Hospital of Southern Medical University, Guangzhou, Guangdong Province 510282, China
| | - Tian-Pei Guan
- Department of Hepatobiliary Surgery, ZhuJiang Hospital of Southern Medical University, Guangzhou, Guangdong Province 510282, China
| | - Jian Yang
- Department of Hepatobiliary Surgery, ZhuJiang Hospital of Southern Medical University, Guangzhou, Guangdong Province 510282, China
| | - Chi-Hua Fang
- Department of Hepatobiliary Surgery, ZhuJiang Hospital of Southern Medical University, Guangzhou, Guangdong Province 510282, China.
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Algarni AA, Alshuhri AH, Alonazi MM, Mourad MM, Bramhall SR. Focal liver lesions found incidentally. World J Hepatol 2016; 8:446-451. [PMID: 27028805 PMCID: PMC4807306 DOI: 10.4254/wjh.v8.i9.446] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2015] [Revised: 01/23/2016] [Accepted: 03/14/2016] [Indexed: 02/06/2023] Open
Abstract
Incidentally found focal liver lesions are a common finding and a reason for referral to hepatobiliary service. They are often discovered in patients with history of liver cirrhosis, colorectal cancer, incidentally during work up for abdominal pain or in a trauma setting. Specific points should considered during history taking such as risk factors of liver cirrhosis; hepatitis, alcohol consumption, substance exposure or use of oral contraceptive pills and metabolic syndromes. Full blood count, liver function test and tumor markers can act as a guide to minimize the differential diagnosis and to categorize the degree of liver disease. Imaging should start with B-mode ultrasound. If available, contrast enhanced ultrasound is a feasible, safe, cost effective option and increases the ability to reach a diagnosis. Contrast enhanced computed tomography should be considered next. It is more accurate in diagnosis and better to study anatomy for possible operation. Contrast enhanced magnetic resonance is the gold standard with the highest sensitivity. If doubt still remains, the options are biopsy or surgical excision.
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Hennedige T, Venkatesh SK. Advances in computed tomography and magnetic resonance imaging of hepatocellular carcinoma. World J Gastroenterol 2016; 22:205-220. [PMID: 26755871 PMCID: PMC4698486 DOI: 10.3748/wjg.v22.i1.205] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2015] [Revised: 08/04/2015] [Accepted: 12/01/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Imaging is important for establishing a diagnosis of HCC and early diagnosis is imperative as several potentially curative treatments are available when HCC is small. Hepatocarcinogenesis occurs in a stepwise manner on a background of chronic liver disease or cirrhosis wherein multiple genes are altered resulting in a range of cirrhosis-associated nodules. This progression is related to increased cellularity, neovascularity and size of the nodule. An understanding of the stepwise progression may aid in early diagnosis. Dynamic and multiphase contrast-enhanced computed tomography and magnetic resonance imaging still form the cornerstone in the diagnosis of HCC. An overview of the current diagnostic standards of HCC in accordance to the more common practicing guidelines and their differences will be reviewed. Ancillary features contribute to diagnostic confidence and has been incorporated into the more recent Liver Imaging Reporting and Data System. The use of hepatocyte-specific contrast agents is increasing and gradually changing the standard of diagnosis of HCC; the most significant benefit being the lack of uptake in the hepatocyte phase in the earlier stages of HCC progression. An outline of supplementary techniques in the imaging of HCC will also be reviewed.
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Umar NK, Badshah MB, Sandrasegaran K, Ghabril M, Agarwal S, Tann M, Lacerda M, Kwo PY. The Presence of Portal Vein Thrombosis Alters the Classic Enhancement Associated with Diagnosis of Hepatocellular Carcinoma. Dig Dis Sci 2015; 60:2196-200. [PMID: 25777258 DOI: 10.1007/s10620-015-3587-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2014] [Accepted: 02/09/2015] [Indexed: 02/07/2023]
Abstract
AIMS To determine whether the presence of portal vein thrombosis (PVT) where venous flow within the liver may be altered may delay the diagnosis of HCC and be associated with more advanced disease. We characterized the incidence and imaging characteristics of patients diagnosed with hepatocellular carcinoma in a cohort of patients with PVT compared with those without PVT. METHODS This is a single-center retrospective study of a subset of HCC patients who underwent dynamic imaging for HCC screening and were found to have PVT. Data abstracted included demographic data, TNM stage, number/type of scans, AFP level, MELD score, and time to diagnosis. RESULTS Eighty-two patients newly diagnosed with HCC on screening were reviewed, of which 37 % (30/82) were found to have portal vein thrombosis. Patients with PVT had higher rates of atypical imaging associated with HCC compared with those without PVT (83 vs 56 %, p = 0.01) and had lower rates of portal venous washout (23 % vs 50 %, p = 0.018). Patients with PVT and HCC were also diagnosed at later TNM stage than those without PVT (70 vs 23 %, p < 0.001) and were significantly less likely to receive orthotopic liver transplant (3.6 vs 42 %, p < 0.001). Fourteen patients had preexisting PV clot without HCC; 16 developed PVT during screening or at diagnosis. Those with preexisting PVT were older (63. vs 55 years) and had higher rates of diagnosis of HCC using MRI (79 vs 21 % with CT, p = 0.01), compared with those without preexisting PVT. CONCLUSION The presence of PVT found on dynamic imaging was associated with advanced stage of HCC at the time of diagnosis. Clinicians should have a high suspicion for HCC diagnosis in new liver lesions with atypical enhancement in the setting of PVT. In this setting, MRI was more frequently associated with HCC diagnosis.
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Affiliation(s)
- Nadia K Umar
- Department of Medicine, Indiana University School of Medicine, 975W. Walnut, IB 327, Indianapolis, IN, 46202-5121, USA
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Kim HD, Lim YS, Han S, An J, Kim GA, Kim SY, Lee SJ, Won HJ, Byun JH. Evaluation of early-stage hepatocellular carcinoma by magnetic resonance imaging with gadoxetic acid detects additional lesions and increases overall survival. Gastroenterology 2015; 148:1371-82. [PMID: 25733098 DOI: 10.1053/j.gastro.2015.02.051] [Citation(s) in RCA: 107] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2014] [Revised: 02/22/2015] [Accepted: 02/24/2015] [Indexed: 12/27/2022]
Abstract
BACKGROUND & AIMS Hepatocellular carcinoma (HCC) has a high rate of intrahepatic recurrence after curative treatment, possibly because metastases are not always identified before treatment. Magnetic resonance (MR) imaging with a liver-specific contrast agent, gadoxetic acid, can detect small HCCs with high levels of sensitivity. We investigated whether MR imaging with gadoxetic acid increases overall and recurrence-free survival of patients initially assessed by computed tomography (CT). METHODS We performed a retrospective study of data from 700 patients diagnosed with a single-nodular HCC by dynamic 4-phase CT in Seoul, Korea, from January 2009 through December 2010. Of these patients, 323 underwent additional evaluation with gadoxetic acid-enhanced MR imaging (CT+MR group). The 377 patients who did not undergo MR imaging analysis are referred to as the CT group. RESULTS The CT and CT+MR groups were comparable in most baseline characteristics (Child-Pugh class A, 93.1% vs 94.7%; and median size of the primary HCCs, 2.8 vs 2.6 cm, respectively). Seventy-four additional HCC nodules were detected in 53 (16.4%) of the patients who underwent MR evaluation after CT (CT+MR group). These detections increased the Barcelona Clinic Liver Cancer stages for 43 patients (13.3%) and modified their treatment plans. On multivariable analyses, the CT+MR group had a significantly lower rate of HCC recurrence (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.54-0.96) and lower overall mortality (HR, 0.65; 95% CI, 0.44-0.96) than the CT group. In an analysis of 285 pairs of patients matched on the basis of the propensity score, the CT+MR group had significantly lower overall mortality (HR, 0.66; 95% CI, 0.44-0.99). CONCLUSIONS Among patients who underwent dynamic CT analysis of a single-nodular HCC, additional evaluation by MR imaging with gadoxetic acid led to the detection of additional HCC nodules in 16% of patients, reduced the risk of disease recurrence, and decreased overall mortality.
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Affiliation(s)
- Hyung-Don Kim
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young-Suk Lim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Seungbong Han
- Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jihyun An
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Gi-Ae Kim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - So Yeon Kim
- Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - So Jung Lee
- Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hyung Jin Won
- Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jae Ho Byun
- Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Kanefuji T, Takano T, Suda T, Akazawa K, Yokoo T, Kamimura H, Kamimura K, Tsuchiya A, Takamura M, Kawai H, Yamagiwa S, Aoyama H, Nomoto M, Terai S. Factors predicting aggressiveness of non-hypervascular hepatic nodules detected on hepatobiliary phase of gadolinium ethoxybenzyl diethylene-triamine-pentaacetic-acid magnetic resonance imaging. World J Gastroenterol 2015; 21:4583-4591. [PMID: 25914467 PMCID: PMC4402305 DOI: 10.3748/wjg.v21.i15.4583] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2014] [Revised: 11/29/2014] [Accepted: 01/16/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To establish a prognostic formula that distinguishes non-hypervascular hepatic nodules (NHNs) with higher aggressiveness from less hazardous one. METHODS Seventy-three NHNs were detected in gadolinium ethoxybenzyl diethylene-triamine-pentaacetic-acid magnetic resonance imaging (Gd-EOB-DTPA-MRI) study and confirmed to change 2 mm or more in size and/or to gain hypervascularity. All images were interpreted independently by an experienced, board-certified abdominal radiologist and hepatologist; both knew that the patients were at risk for hepatocellular carcinoma development but were blinded to the clinical information. A formula predicting NHN destiny was developed using a generalized estimating equation model with thirteen explanatory variables: age, gender, background liver diseases, Child-Pugh class, NHN diameter, T1-weighted imaging/T2-weighted imaging detectability, fat deposition, lower signal intensity in arterial phase, lower signal intensity in equilibrium phase, α-fetoprotein, des-γ-carboxy prothrombin, α-fetoprotein-L3, and coexistence of classical hepatocellular carcinoma. The accuracy of the formula was validated in bootstrap samples that were created by resampling of 1000 iterations. RESULTS During a median follow-up period of 504 d, 73 NHNs with a median diameter of 9 mm (interquartile range: 8-12 mm) grew or shrank by 68.5% (fifty nodules) or 20.5% (fifteen nodules), respectively, whereas hypervascularity developed in 38.4% (twenty eight nodules). In the fifteen shrank nodules, twelve nodules disappeared, while 11.0% (eight nodules) were stable in size but acquired vascularity. A generalized estimating equation analysis selected five explanatories from the thirteen variables as significant factors to predict NHN progression. The estimated regression coefficients were 0.36 for age, 6.51 for lower signal intensity in arterial phase, 8.70 or 6.03 for positivity of hepatitis B virus or hepatitis C virus, 9.37 for des-γ-carboxy prothrombin, and -4.05 for fat deposition. A formula incorporating the five coefficients revealed sensitivity, specificity, and accuracy of 88.0%, 86.7%, and 87.7% in the formulating cohort, whereas these of 87.2% ± 5.7%, 83.8% ± 13.6%, and 87.3% ± 4.5% in the bootstrap samples. CONCLUSION These data suggest that the formula helps Gd-EOB-DTPA-MRI detect a trend toward hepatocyte transformation by predicting NHN destiny.
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Suzuki K, Okuda Y, Ota M, Kojima F, Horimoto M. Diagnosis of hepatocellular carcinoma nodules in patients with chronic liver disease using contrast-enhanced sonography: usefulness of the combination of arterial- and kupffer-phase enhancement patterns. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2015; 34:423-433. [PMID: 25715363 DOI: 10.7863/ultra.34.3.423] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
OBJECTIVES To determine the usefulness of contrast-enhanced sonography using the perfluorobutane contrast agent Sonazoid (Daiichi-Sankyo, Tokyo, Japan) for establishing the diagnosis and cellular differentiation of hepatocellular carcinoma in patients with chronic liver disease. METHODS Patients with chronic liver disease in whom hepatic nodules were detected during screening for hepatocellular carcinoma were examined by imaging modalities, including contrast-enhanced computed tomography (CT), contrast-enhanced sonography, and contrast-enhanced magnetic resonance imaging. Nodules with negative imaging findings were further investigated with core biopsy or followed at our hospital. Between April 2007 and March 2011, all patients with hepatic nodules who underwent core biopsy of the nodules or hepatic resection for hepatocellular carcinoma were reviewed. Fifty-nine nodules from 47 patients with 42 contrast-enhanced sonographic findings and 41 contrast-enhanced CT findings were examined. Arterial- and Kupffer-phase enhancement patterns of the nodules on contrast-enhanced sonography were compared with the diagnosis and cellular differentiation of hepatocellular carcinoma. Arterial- and late-phase enhancement patterns on contrast-enhanced CT were also compared with histologic findings. RESULTS The combination of hyperenhancement in the arterial phase and hypoenhancement in the Kupffer phase on contrast-enhanced sonography (n = 11) correlated with moderately differentiated hepatocellular carcinoma (P = .0028, Fisher exact test). The combination of hypoenhancement in the arterial phase and isoenhancement in the Kupffer phase on contrast-enhanced sonography (n = 14) correlated with well-differentiated hepatocellular carcinoma (P = .0006, Fisher exact test). The combination of high density in the arterial phase and low density in the late phase on contrast-enhanced CT (n = 21) correlated with moderately differentiated hepatocellular carcinoma (P = .0059, Fisher exact test), but no enhancement pattern combination on contrast-enhanced CT correlated with well-differentiated hepatocellular carcinoma. CONCLUSIONS Sonazoid contrast-enhanced sonography is useful for diagnosis of well-differentiated hepatocellular carcinoma.
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Affiliation(s)
- Kunio Suzuki
- Departments of Gastroenterology (K.S., Y.O., M.O., M.H.) and Pathology (F.K.), Saiseikai Senri Hospital, Osaka, Japan.
| | - Yorihide Okuda
- Departments of Gastroenterology (K.S., Y.O., M.O., M.H.) and Pathology (F.K.), Saiseikai Senri Hospital, Osaka, Japan
| | - Makiyo Ota
- Departments of Gastroenterology (K.S., Y.O., M.O., M.H.) and Pathology (F.K.), Saiseikai Senri Hospital, Osaka, Japan
| | - Fumiyoshi Kojima
- Departments of Gastroenterology (K.S., Y.O., M.O., M.H.) and Pathology (F.K.), Saiseikai Senri Hospital, Osaka, Japan
| | - Masayoshi Horimoto
- Departments of Gastroenterology (K.S., Y.O., M.O., M.H.) and Pathology (F.K.), Saiseikai Senri Hospital, Osaka, Japan
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Hwang J, Kim YK, Kim JM, Lee WJ, Choi D, Hong SS. Pretransplant diagnosis of hepatocellular carcinoma by gadoxetic acid-enhanced and diffusion-weighted magnetic resonance imaging. Liver Transpl 2014; 20:1436-46. [PMID: 25103727 DOI: 10.1002/lt.23974] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2014] [Revised: 06/19/2014] [Accepted: 07/31/2014] [Indexed: 01/12/2023]
Abstract
We sought to evaluate the diagnostic performance of gadoxetic acid-enhanced magnetic resonance imaging (MRI) with and without additional diffusion-weighted imaging (DWI) in the detection of hepatocellular carcinoma (HCC) in pretransplant patients. We included 63 liver transplant patients (54 men and 9 women; mean age = 52 years) who had undergone gadoxetic acid-enhanced MRI with DWI at 3.0 T within 90 days before transplantation. Two image sets were reviewed for HCC in 2 separate sessions by 2 independent observers: the gadoxetic acid set and the combined set (gadoxetic acid plus DWI). The sensitivity, specificity, positive predictive value, and negative predictive value were calculated for each image set. In all, 113 HCCs (size range = 0.5-7.8 cm, mean = 2.0 ± 1.3 cm) were identified in the 52 liver explants. The per-lesion sensitivity of the combined set (78.8% for both observers) was higher than the sensitivity of the gadoxetic acid set [71.7% (P = 0.02) and 72.6% (P = 0.03) for the 2 observers], with the highest trend for Child-Pugh class A (94.4% and 97.2% for gadoxetic acid and 97.2% for combined), which was followed by class B (73.2% for gadoxetic acid and 82.9% for combined) and then class C (47.2% for gadoxetic acid and 55.6% for combined, P = 0.01). The per-patient negative predictive value of the combined set was higher than that of the gadoxetic acid set for both observers (P = 0.046). There was no difference in specificity between the 2 image sets (P > 0.05). The addition of DWI to gadoxetic acid-enhanced MRI resulted in significantly higher sensitivity to detect HCC. However, the sensitivity decreased with increasing cirrhosis severity for both imaging types.
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Affiliation(s)
- Jiyoung Hwang
- Department of Radiology, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea
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Ronot M, Vilgrain V. Hepatocellular carcinoma: diagnostic criteria by imaging techniques. Best Pract Res Clin Gastroenterol 2014; 28:795-812. [PMID: 25260309 DOI: 10.1016/j.bpg.2014.08.005] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2014] [Revised: 07/12/2014] [Accepted: 08/15/2014] [Indexed: 01/31/2023]
Abstract
Imaging plays a very important role in the diagnosis of HCC. Indeed, in high-risk patients a noninvasive diagnosis can only be obtained by imaging in presence of typical features. These features include arterial enhancement followed by washout during the portal venous and/or delayed phases on CT scan or MRI. This pattern is quite specific and has been endorsed by both Western and Asian diagnostic guidelines. However, its sensitivity is not very high, especially for small lesions. Therefore ancillary signs may be needed to increase the reliability of the diagnosis. Recent hepatobiliary MRI contrast agents seem to be interesting to improve characterization of small nodules in the cirrhotic liver.
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Affiliation(s)
- Maxime Ronot
- Department of Radiology, APHP, University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, Hauts-de-Seine, France; University Paris Diderot, Sorbonne Paris Cité, Paris, France; INSERM U1149, centre de recherche biomédicale Bichat-Beaujon, CRB3, Paris, France.
| | - Valérie Vilgrain
- Department of Radiology, APHP, University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, Hauts-de-Seine, France; University Paris Diderot, Sorbonne Paris Cité, Paris, France; INSERM U1149, centre de recherche biomédicale Bichat-Beaujon, CRB3, Paris, France
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15
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Teixera SR, Kohan AA, Paspulati RM, Rong R, Herrmann KA. Potential Role of Positron Emission Tomography/Magnetic Resonance Imaging in Gastrointestinal and Abdominal Malignancies: Preliminary Experience. Semin Roentgenol 2014; 49:321-33. [DOI: 10.1053/j.ro.2014.07.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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16
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Li RK, Zhao J, Rao SX, Chen CZ, Zeng MS, Qiang JW. Primary hepatic neuroendocrine carcinoma: MR imaging findings including preliminary observation on diffusion-weighted imaging. ACTA ACUST UNITED AC 2014; 38:1269-76. [PMID: 23942951 DOI: 10.1007/s00261-013-0029-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
PURPOSE To investigate MR imaging findings of primary hepatic neuroendocrine carcinoma (PHNEC) including preliminary observations on diffusion-weighted imaging (DWI). MATERIALS AND METHODS MR images of eight patients with pathologically confirmed PHNEC were retrospectively analyzed. The morphological characteristics and dynamic enhancement patterns were evaluated. RESULTS One case showed a well-defined solitary nodule with homogenous hypointensity on T1-weighted imaging (T1WI) and hyperintensity on T2-weighted imaging (T2WI) and DWI. The remaining seven cases appeared as well-defined dominant masses with multiple satellite nodules. The dominant masses demonstrated heterogeneous hypointensity on T1WI and hyperintensity on T2WI, which all appeared as a marked enhancement at arterial phase and rapid washout at portal venous phase. Six cases demonstrated rim-like enhancement at equilibrium phase. The satellite lesions showed heterogeneous hypointensity on T1WI and marked hyperintensity on T2WI with variable enhancements, such as homogeneous, rim-like enhancement. All the dominant masses and satellite nodules appeared as markedly hyperintensity and reduced apparent coefficient (ADCs) values on DWI. The mean ADC value of the tumors was significantly lower than that of surrounding liver parenchyma (1.02 ± 0.57 vs. 2.24 × 10(-3) mm(2)/s, p = 0.000). CONCLUSION PHNECs typically appear as a large dominant hypervascular mass accompanied by satellite nodules, with rapid washout and capsular enhancement on dynamic MR imaging and restricted diffusion on DWI.
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Affiliation(s)
- Ruo-Kun Li
- Department of Radiology, Jinshan Hospital, Shanghai School of Medicine, Fudan University, 1508 Longhang Road, Shanghai, 201508, China
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17
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Cyran CC, Paprottka PM, Eisenblätter M, Clevert DA, Rist C, Nikolaou K, Lauber K, Wenz F, Hausmann D, Reiser MF, Belka C, Niyazi M. Visualization, imaging and new preclinical diagnostics in radiation oncology. Radiat Oncol 2014; 9:3. [PMID: 24387195 PMCID: PMC3903445 DOI: 10.1186/1748-717x-9-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2013] [Accepted: 12/20/2013] [Indexed: 12/21/2022] Open
Abstract
Innovative strategies in cancer radiotherapy are stimulated by the growing knowledge on cellular and molecular tumor biology, tumor pathophysiology, and tumor microenvironment. In terms of tumor diagnostics and therapy monitoring, the reliable delineation of tumor boundaries and the assessment of tumor heterogeneity are increasingly complemented by the non-invasive characterization of functional and molecular processes, moving preclinical and clinical imaging from solely assessing tumor morphology towards the visualization of physiological and pathophysiological processes. Functional and molecular imaging techniques allow for the non-invasive characterization of tissues in vivo, using different modalities, including computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, positron emission tomography (PET) and optical imaging (OI). With novel therapeutic concepts combining optimized radiotherapy with molecularly targeted agents focusing on tumor cell proliferation, angiogenesis, and cell death, the non-invasive assessment of tumor microcirculation and tissue water diffusion, together with strategies for imaging the mechanisms of cellular injury and repair is of particular interest. Characterizing the tumor microenvironment prior to and in response to irradiation will help to optimize the outcome of radiotherapy. These novel concepts of personalized multi-modal cancer therapy require careful pre-treatment stratification as well as a timely and efficient therapy monitoring to maximize patient benefit on an individual basis. Functional and molecular imaging techniques are key in this regard to open novel opportunities for exploring and understanding the underlying mechanisms with the perspective to optimize therapeutic concepts and translate them into a personalized form of radiotherapy in the near future.
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Affiliation(s)
- Clemens C Cyran
- Department of Clinical Radiology, Laboratory of Experimental Radiology, University of Munich Hospitals, Campus Großhadern, Marchioninistraße 15, 81377 Munich, Germany.
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Indeterminate Observations (Liver Imaging Reporting and Data System Category 3) on MRI in the Cirrhotic Liver: Fate and Clinical Implications. AJR Am J Roentgenol 2013; 201:993-1001. [DOI: 10.2214/ajr.12.10007] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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Characterization of incidental liver lesions: comparison of multidetector CT versus Gd-EOB-DTPA-enhanced MR imaging. PLoS One 2013; 8:e66141. [PMID: 23776623 PMCID: PMC3679037 DOI: 10.1371/journal.pone.0066141] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2013] [Accepted: 05/02/2013] [Indexed: 12/11/2022] Open
Abstract
As a result of recent developments in imaging modalities and wide spread routine medical checkups and screening, more incidental liver lesions are found frequently on US these days. When incidental liver lesions are found on US, physicians have to make a decision whether to just follow up or to undergo additional imaging studies for lesion characterization. In order to choose the next appropriate imaging modality, the diagnostic accuracy of each imaging study needs to be considered. Therefore, we tried to compare the accuracy of contrast-enhanced multidetector CT (MDCT) and Gd-EOB-DTPA-enhanced MRI for characterization of incidental liver masses. We included 127 incidentally found focal liver lesions (94 benign and 33 malignant) from 80 patients (M∶F = 45∶35) without primary extrahepatic malignancy or chronic liver disease. Two radiologists independently reviewed Gd-EOB-DTPA-enhanced MRI and MDCT. The proportion of confident interpretations for differentiation of benign and malignant lesions and for the specific diagnosis of diseases were compared. The proportion of confident interpretations for the differentiation of benign and malignant lesions was significantly higher with EOB-MRI(94.5%-97.6%) than with MDCT (74.0%-92.9%). In terms of specific diagnosis, sensitivity and accuracy were significantly higher with EOB-MRI than with MDCT for the diagnosis of focal nodular hyperplasia (FNH) and focal eosinophilic infiltration. The diagnoses of the remaining diseases were comparable between EOB-MRI and MDCT. Hence, our results suggested that Gd-EOB-MRI may provide a higher proportion of confident interpretations than MDCT, especially for the diagnosis of incidentally found FNH and focal eosinophilic infiltration.
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20
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Hennedige T, Venkatesh SK. Imaging of hepatocellular carcinoma: diagnosis, staging and treatment monitoring. Cancer Imaging 2013; 12:530-547. [PMID: 23400006 PMCID: PMC3666429 DOI: 10.1102/1470-7330.2012.0044] [Citation(s) in RCA: 126] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/23/2012] [Indexed: 12/11/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Imaging is important for establishing a diagnosis of HCC. Several imaging modalities including ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and angiography are used in evaluating patients with chronic liver disease and suspected HCC. CT, MRI and contrast-enhanced US have replaced biopsy for diagnosis of HCC. Dynamic multiphase contrast-enhanced CT or MRI is the current standard for imaging diagnosis of HCC. Functional imaging techniques such as perfusion CT and diffusion-weighted MRI provide additional information about tumor angiogenesis that may be useful for treatment. Techniques evaluating tissue mechanical properties such as magnetic resonance elastography, and acoustic radiation force impulse imaging are being explored for characterizing liver lesions. The role of PET in the evaluation of HCC is evolving with promise seen especially with the use of a hepatocyte-specific PET tracer. Imaging is also critical for assessment of treatment response and detection of recurrence following locoregional treatment. Knowledge of the post-treatment appearance of HCC is essential for correct interpretation. This review article provides an overview of the role of imaging in the diagnosis, staging and post-treatment follow-up of HCC.
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Affiliation(s)
- Tiffany Hennedige
- Diagnostic Imaging, National University Hospital, National University Health System, Singapore
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21
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Hyperintense lesions on gadoxetate disodium-enhanced hepatobiliary phase imaging. AJR Am J Roentgenol 2013; 199:W575-86. [PMID: 23096201 DOI: 10.2214/ajr.11.8205] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE The purpose of this article is to illustrate various focal hepatic lesions that may show hyperintensity on hepatobiliary phase images on gadoxetate disodium-enhanced MRI. CONCLUSION Hyperintense lesions on gadoxetate disodium-enhanced MRI include focal nodular hyperplasia (FNH) or FNH-like nodules, hepatocellular adenoma, dysplastic nodules, and hepatocellular carcinoma. Understanding the contrast enhancement patterns on hepatobiliary phase images and other imaging findings is important to ensure correct diagnosis.
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22
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Kim YK, Lee WJ, Park MJ, Kim SH, Rhim H, Choi D. Hypovascular hypointense nodules on hepatobiliary phase gadoxetic acid-enhanced MR images in patients with cirrhosis: potential of DW imaging in predicting progression to hypervascular HCC. Radiology 2012; 265:104-14. [PMID: 22891358 DOI: 10.1148/radiol.12112649] [Citation(s) in RCA: 111] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
PURPOSE To investigate the imaging features of hypovascular hypointense nodules on hepatobiliary phase gadoxetic acid-enhanced magnetic resonance (MR) images in patients with cirrhosis that may be associated with progression to hypervascular hepatocellular carcinoma (HCC). MATERIALS AND METHODS The institutional review board approved this retrospective study and waived informed patient consent. This study included 135 patients with a diagnosis of hepatitis B-induced liver cirrhosis and 214 hypovascular hypointense nodules on hepatobiliary phase gadoxetic acid-enhanced MR images. MR images were analyzed with respect to nodule size, degree of hypointensity at hepatobiliary phase (four grades), presence of fat, and signal intensity on T1- and T2-weighted and diffusion-weighted (DW) images. Univariate and multivariate Cox regression analyses were used to identify variables that are associated with developing hypervascular HCC. RESULTS On follow-up MR images, 139 nodules (65.0%) had no evidence of HCC (mean follow-up, 522 days) (group 1), but 75 (35.0%) became hypervascular HCC (mean follow-up, 388 days) (group 2). Univariable Cox analysis revealed that the degree of hypointensity on hepatobiliary phase images (P=.044 and .001) and hyperintensity on T2-weighted and DW images (P=.001 and .0001) was significantly related to the development of hypervascular HCC. According to the multivariable Cox analysis, no other variable significantly adjusted the model once hyperintensity at initial DW imaging was already included as an associated variable, (hazard ratio, 7.44; 95% confidence interval: 4.28, 12.94; P=.0001). CONCLUSION Hyperintensity on DW images in hypovascular hypointense nodules on hepatobiliary phase gadoxetic acid-enhanced MR images in patients with cirrhosis is strongly associated with progression to hypervascular HCC.
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Affiliation(s)
- Young Kon Kim
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea
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Nikolaou K, Cyran CC, Lauber K, Reiser MF, Clevert DA. [Preclinical imaging in animal models of radiation therapy]. Radiologe 2012; 52:252-62. [PMID: 22382437 DOI: 10.1007/s00117-011-2194-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
CLINICAL/METHODICAL ISSUE Modern radiotherapy benefits from precise and targeted diagnostic and pretherapeutic imaging. STANDARD RADIOLOGICAL METHODS Standard imaging modalities, such as computed tomography (CT) offer high morphological detail but only limited functional information on tumors. METHODICAL INNOVATIONS Novel functional and molecular imaging modalities provide biological information about tumors in addition to detailed morphological information. PERFORMANCE Perfusion magnetic resonance imaging (MRI) CT or ultrasound-based perfusion imaging as well as hybrid modalities, such as positron emission tomography (PET) CT or MRI-PET have the potential to identify and precisely delineate viable and/or perfused tumor areas, enabling optimization of targeted radiotherapy. Functional information on tissue microcirculation and/or glucose metabolism allow a more precise definition and treatment of tumors while reducing the radiation dose and sparing the surrounding healthy tissue. ACHIEVEMENTS In the development of new imaging methods for planning individualized radiotherapy, preclinical imaging and research plays a pivotal role, as the value of multimodality imaging can only be assessed, tested and adequately developed in a preclinical setting, i.e. in animal tumor models. PRACTICAL RECOMMENDATIONS New functional imaging modalities will play an increasing role for the surveillance of early treatment response during radiation therapy and in the assessment of the potential value of new combination therapies (e.g. combining anti-angiogenic drugs with radiotherapy).
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Affiliation(s)
- K Nikolaou
- Institut für Klinische Radiologie, Klinikum der Ludwig-Maximilians-Universität, Campus Grosshadern, Marchioninistr. 15, 81377 München.
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Abstract
Gadolinium ethoxybenzyl dimeglumine (Gd-EOB-DTPA, Primovist in Europe and Eovist in the USA) is a liver-specific magnetic resonance imaging contrast agent that has up to 50% hepatobiliary excretion in the normal liver. After intravenous injection, Gd-EOB-DTPA distributes into the vascular and extravascular spaces during the arterial, portal venous and late dynamic phases, and progressively into the hepatocytes and bile ducts during the hepatobiliary phase. The hepatocyte uptake of Gd-EOB-DTPA mainly occurs via the organic anion transporter polypeptides OATP1B1 and B3 located at the sinusoidal membrane and biliary excretion via the multidrug resistance-associated proteins MRP2 at the canalicular membrane. Because of these characteristics, Gd-EOB-DTPA behaves similarly to non-specific gadolinium chelates during the dynamic phases, and adds substantial information during the hepatobiliary phase, improving the detection and characterization of focal liver lesions and diffuse liver disease. This information is particularly relevant for the detection of metastases, and for the detection and characterization of nodular lesions in liver cirrhosis, including early hepatocellular carcinomas. Finally, GD-EOB-DTPA-enhanced magnetic resonance imaging may provide quantitative assessment regarding liver perfusion and hepatocyte function in diffuse liver diseases. The full potential of GD-EOB-DTPA-enhanced magnetic resonance imaging has to be established further. It is already clear that GD-EOB-DTPA-enhanced magnetic resonance imaging provides anatomic and functional information in the setting of focal and diffuse liver disease that is unattainable with magnetic resonance imaging enhanced with non-specific contrast agents.
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25
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Hidaka M, Takatsuki M, Okudaira S, Soyama A, Muraoka I, Tanaka T, Yamaguchi I, Hara T, Miyaaki H, Ichikawa T, Hayashi T, Sakamoto I, Nakao K, Kuroki T, Kanematsu T, Eguchi S. The expression of transporter OATP2/OATP8 decreases in undetectable hepatocellular carcinoma by Gd-EOB-MRI in the explanted cirrhotic liver. Hepatol Int 2012. [DOI: 10.1007/s12072-012-9379-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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Wong KF, Luk JM. Discovery of lamin B1 and vimentin as circulating biomarkers for early hepatocellular carcinoma. Methods Mol Biol 2012; 909:295-310. [PMID: 22903723 DOI: 10.1007/978-1-61779-959-4_19] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
The recent advancements in proteomic technologies have reconstituted our research strategies over different type of liver diseases including hepatocellular carcinoma (HCC). Combined analyses on HCC proteome and clinicopathological data of patients have allowed identification of many promising biomarkers that can be further developed into noninvasive diagnostic assays for cancer surveillance. Capitalizing our established proteomic platform primarily based on two-dimensional polyacrylamide gel electrophoresis (2DE) and MALDI-TOF/TOF mass spectrometry, our groups have identified lamin B1 (LMNB1) and vimentin (VIM) as promising biomarkers for detection of early HCC. Protein levels of both biomarkers were significantly elevated in cancerous tissues when compared to the controls in disease-free and cirrhotic liver subjects. Further investigation of the circulating LMNB1 mRNA level in patients' blood samples by standard PCR showed 76% sensitivity and 82% specificity for detection of early HCC. In parallel, an ELISA assay for measuring circulating vimentin level in patients' serum samples could detect small HCC at 40.91% sensitivity and 87.5% specificity. The candidate biomarkers were evaluated with the diagnostic performance of α-fetoprotein (AFP) for HCC. In this article, we address the current protocols for HCC biomarker discovery, ranging from clinical sample preparation, 2DE proteomic profiling and informatics analysis, and assay development and clinical validation study. Focus is emphasized on the methods for sample preservation and low-abundance protein enrichment.
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Affiliation(s)
- Kwong-Fai Wong
- Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
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Kim MJ, Lee M, Choi JY, Park YN. Imaging features of small hepatocellular carcinomas with microvascular invasion on gadoxetic acid-enhanced MR imaging. Eur J Radiol 2011; 81:2507-12. [PMID: 22137613 DOI: 10.1016/j.ejrad.2011.11.014] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2011] [Revised: 11/02/2011] [Accepted: 11/03/2011] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Detection of hepatocellular carcinomas (HCCs) before microvascular invasion (MVI) occurs is important due to the poor outcomes associated with MVI. We retrospectively investigated the imaging features of small HCCs with MVI on gadoxetic acid-enhanced MR imaging. METHODS Fifty patients (40 men and 10 women; mean age, 54 years) with 58 surgically proven small (2 cm or less) HCCs were evaluated by gadoxetic acid-enhanced MRI. Signal intensities on imaging sequences and the presence of the typical dynamic enhancement pattern (arterial enhancement and washout) were assessed. Fisher's exact tests were performed to evaluate the relationships between the presence of MVI, tumor size, and imaging findings. RESULTS None of the 12 small HCCs with diameters of 1cm or less had MVI, while 15 (33%) of the 46 small HCCs with diameters of 1.1-2.0 cm had MVI (p=0.025, Fisher's exact test). Among the small HCCs with diameters of 1.1-2.0 cm, all HCCs with MVI showed the typical dynamic pattern and hyperintensity on T2- and diffusion-weighted images. Most HCCs (54 lesions, 93%) were hypointense on hepatobiliary phase images regardless of the presence of MVI. CONCLUSIONS All small HCCs with MVI showed typical dynamic pattern and hyperintensity on T2-weighted and diffusion-weighted images, while atypical dynamic pattern and size of less than 1cm in diameter may suggest absence of MVI.
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Affiliation(s)
- Myeong-Jin Kim
- Department of Radiology and Research Institute of Radiological Science, Yonsei University Severance Hospital, Seoul, South Korea.
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