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Dumenci OE, U AM, Khan SA, Holmes E, Taylor-Robinson SD. Exploring Metabolic Consequences of CPS1 and CAD Dysregulation in Hepatocellular Carcinoma by Network Reconstruction. J Hepatocell Carcinoma 2020; 7:1-9. [PMID: 32021853 PMCID: PMC6955626 DOI: 10.2147/jhc.s239039] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Accepted: 12/19/2019] [Indexed: 01/05/2023] Open
Abstract
Purpose Hepatocellular carcinoma (HCC) is the fourth commonest cause of cancer-related mortality; it is associated with various genetic alterations, some involved in metabolic reprogramming. This study aimed to explore the potential metabolic impact of Carbamoyl Phosphate Synthase I (CPS1) and carbamoyl phosphate synthetase/aspartate transcarbamoylase/dihydroorotase (CAD) dysregulation through the reconstruction of a network that integrates information from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, Human Metabolome Database (HMDB) and Human Protein Atlas (HPA). Methods and results Existing literature was used to determine the roles of CPS1 and CAD in HCC. CPS1 downregulation is thought to play a role in hepatocarcinogenesis through an increased glutamine availability for de novo pyrimidine biosynthesis, which CAD catalyzes the first three steps for. KEGG, HMDB and HPA were used to reconstruct a network of relevant pathways, demonstrating the relationships between genes and metabolites using the MetaboSignal package in R. The network was filtered to exclude any duplicates, and those greater than three steps away from CPS1 or CAD. Consequently, a network of 18 metabolites, 28 metabolic genes and 1 signaling gene was obtained, which indicated expression profiles and prognostic information of each gene in the network. Conclusion Information from different databases was collated to form an informative network that integrated different “-omics” approaches, demonstrating the relationships between genetic and metabolic components of urea cycle and the de novo pyrimidine biosynthesis pathway. This study paves the way for further research by acting as a template to investigate the relationships between genes and metabolites, explore their potential roles in various diseases and aid the development of new screening and treatment methods through network reconstruction.
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Kang Z, Wang N, Xu A, Wang L. Digital subtract angiography and lipiodol deposits following embolization in cirrhotic nodules of LIRADS category ≥3. Eur J Radiol Open 2019; 6:106-112. [PMID: 30899770 PMCID: PMC6405901 DOI: 10.1016/j.ejro.2019.02.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Revised: 01/01/2019] [Accepted: 02/09/2019] [Indexed: 10/27/2022] Open
Abstract
PURPOSE To assess the correlation between Liver Imaging Reporting and Data System (LIRADS) and digital substract angiography (DSA) and lipiodol deposits in cirrhotic nodules of LIRADS category ≥3 receiving interventional treatment. METHODS From June 2014 to June 2016, patients with cirrhotic nodules were identified retrospectively and MR images were reviewed by sub-specialty radiologists according to modified LIRADS v2014. Correlation between nodules of LIRADS category ≥3 and DSA findings and lipiodol deposits were analyzed. RESULTS 71 cirrhotic nodules were evaluated in 33 patients. 39/71 nodules were classified as LR-3, 9/71 nodules were categorized as LR-4, 23/71 nodules were grouped into LR-5. 43 nodules presented positive DSA, 37 nodules showed presence of lipiodol deposits during follow up. With the upgrade of LIRADS category of cirrhotic nodules, DSA and lipiodol deposits became more conspicuous. Spearman analysis demonstrated positive correlations between LIRADS and DSA (r = 0.567, P = 0.000) as well as LIRADS and lipiodol deposits (r = 0.616, P = 0.000). ROC analysis revealed a cut-off value of LR ≥ 4 resulted in a sensitivity of 67.4% and specificity of 89.3% in predicting positive DSA (RUC = 0.799, P ＜ 0.0001), and a sensitivity of 75.7% and specificity of 88.2% in predicting lipiodol deposits (RUC = 0.818, P ＜ 0.0001). Of 39 lesions of LR-3, 64.1% (25/39) showed negative DSA, and 76.9% (30/39) showed absence of lipiodol deposits during follow up. Logistic regression analysis identified arterial enhancement (OR = 26.837, P = 0.002) and lesion size (OR = 1.325, P = 0.022) were independently associated with positive DSA in nodule of LIRADS category ≥3, while no factors were associated with lipiodol deposits. CONCLUSION The LIRADS can be used to predict DSA findings and lipiodol deposits in nodules with LIRADS score 3 and above. LIRADS 3 nodules tend to be DSA-negative and have less lipiodol deposits. DSA and lipiodol deposits become more conspicuous in nodules from LIRADS 3 to 5.
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Key Words
- BCLC, Barcelona Clinic Liver Cancer
- DN, dysplastic nodules
- DSA, digital subtract angiography
- DWI, diffusion weighted imaging
- Digital substract angiography
- HCC, hepatocellular carcinoma
- LIRADS, Liver Imaging Reporting and Data System
- LR-M, probably or definitely malignant but not specific for HCC
- Lipiodol deposits
- Liver imaging reporting and data system
- PACS, picture archiving and communication system
- PWI, perfusion weighted imaging
- RIS, radiology information system
- RN, regenerative nodules
- T1WI, T1 weighted imaging
- T2WI, T2 weighted imaging
- TACE, transcatheter arterial chemoembolization
- TAE, transcatheter arterial embolization
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Bellissimo F, Pinzone MR, Cacopardo B, Nunnari G. Diagnostic and therapeutic management of hepatocellular carcinoma. World J Gastroenterol 2015; 21:12003-12021. [PMID: 26576088 PMCID: PMC4641121 DOI: 10.3748/wjg.v21.i42.12003] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Revised: 08/03/2015] [Accepted: 09/30/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is an increasing health problem, representing the second cause of cancer-related mortality worldwide. The major risk factor for HCC is cirrhosis. In developing countries, viral hepatitis represent the major risk factor, whereas in developed countries, the epidemic of obesity, diabetes and nonalcoholic steatohepatitis contribute to the observed increase in HCC incidence. Cirrhotic patients are recommended to undergo HCC surveillance by abdominal ultrasounds at 6-mo intervals. The current diagnostic algorithms for HCC rely on typical radiological hallmarks in dynamic contrast-enhanced imaging, while the use of α-fetoprotein as an independent tool for HCC surveillance is not recommended by current guidelines due to its low sensitivity and specificity. Early diagnosis is crucial for curative treatments. Surgical resection, radiofrequency ablation and liver transplantation are considered the cornerstones of curative therapy, while for patients with more advanced HCC recommended options include sorafenib and trans-arterial chemo-embolization. A multidisciplinary team, consisting of hepatologists, surgeons, radiologists, oncologists and pathologists, is fundamental for a correct management. In this paper, we review the diagnostic and therapeutic management of HCC, with a focus on the most recent evidences and recommendations from guidelines.
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Huh J, Kim KW, Kim J, Yu E. Pathology-MRI Correlation of Hepatocarcinogenesis: Recent Update. J Pathol Transl Med 2015; 49:218-29. [PMID: 26018513 PMCID: PMC4440933 DOI: 10.4132/jptm.2015.04.15] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2015] [Accepted: 04/14/2015] [Indexed: 02/07/2023] Open
Abstract
Understanding the important alterations during hepatocarcinogenesis as well as the characteristic magnetic resonance imaging (MRI) and histopathological features will be helpful for managing patients with chronic liver disease and hepatocellular carcinoma. Recent advances in MRI techniques, such as fat/iron quantification, diffusion-weighted images, and gadoxetic acid-enhanced MRI, have greatly enhanced our understanding of hepatocarcinogenesis.
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Affiliation(s)
- Jimi Huh
- Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyung Won Kim
- Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea ; Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jihun Kim
- Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea ; Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Eunsil Yu
- Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea ; Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Mannelli L, Rosenkrantz AB. Focal lesions in the cirrhotic liver. APPLIED RADIOLOGY 2013:17-23. [DOI: 10.37549/ar2025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2025]
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Yu NC, Chaudhari V, Raman SS, Lassman C, Tong MJ, Busuttil RW, Lu DSK. CT and MRI improve detection of hepatocellular carcinoma, compared with ultrasound alone, in patients with cirrhosis. Clin Gastroenterol Hepatol 2011; 9:161-7. [PMID: 20920597 DOI: 10.1016/j.cgh.2010.09.017] [Citation(s) in RCA: 185] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2010] [Accepted: 09/22/2010] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS In patients with cirrhosis, hepatocellular carcinoma (HCC) is detected by ultrasound (US), computed tomography (CT), or magnetic resonance imaging (MRI); US is recommended for screening and surveillance. We performed a retrospective analysis of the abilities of these cross-sectional imaging modalities to detect HCC. METHODS We analyzed data from 638 consecutive adult patients with cirrhosis who received liver transplants within 6 months of imaging at a tertiary care institution. Imaging reports and serum alpha-fetoprotein levels were compared with results from pathology analysis of explants as the reference standard. Sensitivities of US, CT, and MRI were calculated overall and in defined size categories. False-positive imaging results and patient-based specificities were evaluated. RESULTS Of the 638 patients, 225 (35%) had HCC, confirmed by pathology analysis of liver explants. In 23 cases, the lesions were infiltrative or extensively multifocal. In the remaining 202 explants (337 numerable, discrete nodules), respective lesion-based sensitivities of US, CT, and MRI were 46%, 65%, and 72% overall and 21%, 40%, and 47% for small (<2 cm) HCC. The sensitivity of US increased with the availability of CT or MRI data (P = .049); sensitivity values were 62% and 85% for lesions 2-4 and ≥ 4 cm, respectively. Patient-based specificities of US, CT, and MRI were 96%, 96%, and 87%, respectively. CONCLUSIONS US, CT, and MRI did not detect small HCC lesions with high levels of sensitivity, although CT and MRI provide substantial improvements over unenhanced US in patients with cirrhosis who received liver transplants.
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Affiliation(s)
- Nam C Yu
- Department of Radiology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA
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Thomas MB, Jaffe D, Choti MM, Belghiti J, Curley S, Fong Y, Gores G, Kerlan R, Merle P, O'Neil B, Poon R, Schwartz L, Tepper J, Yao F, Haller D, Mooney M, Venook A. Hepatocellular carcinoma: consensus recommendations of the National Cancer Institute Clinical Trials Planning Meeting. J Clin Oncol 2010; 28:3994-4005. [PMID: 20679622 DOI: 10.1200/jco.2010.28.7805] [Citation(s) in RCA: 315] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Hepatocelluar carcinoma (HCC) is the most common primary malignancy of the liver in adults and the third most common cause of cancer death worldwide. The incidence of HCC in the United States is rising steadily because of the prevalence of hepatitis C viral infection and other causes of hepatic cirrhosis. The majority of patients have underlying hepatic dysfunction, which complicates patient management and the search for safe and effective therapies. The Clinical Trials Planning Meeting (CTPM) in HCC was convened by the National Cancer Institute's Gastrointestinal Cancer Steering Committee to identify the key knowledge gaps in HCC and define clinical research priorities. The CTPM structured its review according to current evidence-based treatment modalities in HCC and prioritized the recommendations on the basis of the patient populations representing the greatest unmet medical need.
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Affiliation(s)
- Melanie B Thomas
- Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.
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Klein A, Michalski JC, Morelle W. Modifications of human total serum N
-glycome during liver fibrosis-cirrhosis, is it all about immunoglobulins? Proteomics Clin Appl 2010; 4:372-8. [DOI: 10.1002/prca.200900151] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2009] [Revised: 10/21/2009] [Accepted: 12/03/2009] [Indexed: 01/22/2023]
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Kim YI, Chung JW. Selective or targeted gene/drug delivery for liver tumors: advantages and current status of local delivery. Expert Rev Gastroenterol Hepatol 2008; 2:791-802. [PMID: 19090739 DOI: 10.1586/17474124.2.6.791] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
There are various disorders involving the liver. They include metabolic diseases, hepatitis, liver cirrhosis and cancer, the latter of which may be the most serious. Delivery of therapeutic genes or drugs should be targeted to either one of the following cells in the liver: hepatocytes, Kupffer cells and tumor endothelial cells, or to the tumor cells themselves. To maximize the therapeutic effect and minimize systemic toxicity or nontarget injuries, the sufficient amount or dose of genes or drugs should be specifically delivered to a target, with minimal exposure in their active forms to nontarget cells. There are diverse strategies to improve selective delivery or targeting efficiency. In this article, we present potential new therapeutic strategies and clinical developments for liver cancer, with a focus on the progress in the localized delivery of therapeutic agents using image-guided procedures.
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Affiliation(s)
- Young Il Kim
- Division of Interventional Radiology, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305-5642, USA.
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Guan YS, Hu Y, Liu Y. Multidetector-row computed tomography in the management of hepatocellular carcinoma with transcatheter arterial chemoembolization. J Gastroenterol Hepatol 2006; 21:941-6. [PMID: 16724976 DOI: 10.1111/j.1440-1746.2006.04474.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
With the introduction of spiral computed tomography and the development of novel imaging technology in recent years, multidetector-row computed tomography (MDCT) has increasingly been used for the diagnosis of various lesions, especially hepatocellular carcinoma (HCC), due to its volume acquisitions, short scanning time, and especially its double-phase scanning nature, which takes advantage of the dual blood supply of liver. Multidetector-row computed tomography is used to classify HCC into several types based on the blood supply and the histological characteristics of HCC. The evaluation of HCC by MDCT provides crucial clues for the doctors to adopt correct clinical management strategies such as the selection of the appropriate dose of lipiodol before transcatheter arterial chemoembolization (TACE) and the prediction of the prognosis of HCC after TACE. The MDCT scanning allows doctors to choose the region of interest and to evaluate the blood supply according to the lipiodol uptake in order to decide whether there is recrudescence and whether a repeated therapy should be taken. This review describes MDCT, its biphasic scanning, its evaluation of blood supply in HCC and the subsequent classification of HCC, its therapeutic significance before TACE and the prognostic value after TACE.
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Affiliation(s)
- Yong-Song Guan
- Department of Interventional Radiology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
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Jang HJ, Lim JH, Lee SJ, Park CK, Park HS, Do YS. Hepatocellular carcinoma: are combined CT during arterial portography and CT hepatic arteriography in addition to triple-phase helical CT all necessary for preoperative evaluation? Radiology 2000; 215:373-80. [PMID: 10796910 DOI: 10.1148/radiology.215.2.r00ma30373] [Citation(s) in RCA: 88] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
PURPOSE To determine whether the combination of CT during arterial portography (CTAP) and CT hepatic arteriography (CTHA) provides an added benefit to triple-phase helical CT (THCT) alone in the preoperative evaluation of hepatocellular carcinoma (HCC). MATERIALS AND METHODS Fifty-two consecutive patients with pathologically proved HCC underwent THCT (hepatic arterial, portal venous, and delayed phases) and combined CTAP and CTHA. Two radiologists reviewed the images in three sessions: first the THCT images alone, then with the CTAP images, and finally all three sets of images. RESULTS There were 73 pathologically confirmed HCCs. Among 72 lesions considered as HCC at THCT, 69 were proved to be HCCs. Of the additional 37 nodules interpreted as HCC at CTAP, only one was confirmed as such. Among the additional 20 lesions presumed to be HCC at combined CTAP and CTHA, only two were proved to be HCCs. The sensitivity was 94% (69 of 73 lesions) at THCT, 96% (70 of 73) with additional CTAP, and 97% (71 of 73) with all three modalities. The positive predictive value was 96% (69 of 72) at THCT, 65% (70 of 107) with additional CTAP, and 80% (71 of 89) with all three modalities. CONCLUSION The use of CTAP and CTHA, in addition to being invasive and costly, resulted in an unacceptably high false-positive rate without a substantial increase in sensitivity. Therefore, CTAP and CTHA are not recommended for preoperative evaluation of HCC; THCT alone is preferred.
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Affiliation(s)
- H J Jang
- Department of Radiology, Samsung Medical Center, College of Medicine, Sungkyunkwan University, 50 Ilwon-dong, Kangnam-ku, Seoul 135-710, Korea
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