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Diagnostics
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Diagnosis of Hepatocellular Carcinoma
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Diagnosis of Hepatocellular Carcinoma

A special issue of Diagnostics (ISSN 2075-4418).

Deadline for manuscript submissions: closed (30 September 2015) | Viewed by 70881

Special Issue Editor

Prof. Dr. Philippe L. Pereira

E-Mail Website
Guest Editor
Clinic of Radiology, Minimally Invasive Therapies and Nuclear Medicine, Faculty of Eberhards-Karls-University Tübingen, SLK-Kliniken GmbH, Academic Hospital of Ruprecht-Karls-University Heidelberg, Am Gesundbrunnen 20-26, 74078 Heilbronn, Germany
Interests: interventional oncology; interventional MRI

Special Issue Information

Dear Colleagues,

Hepatocellular carcinoma (HCC) is the sixth most common cancer and currently the third leading cause of cancer-related death worldwide. In previous periods, diagnosis of HCC was usually made at advanced stages of the disease. In recent decades, screening of patients with cirrhotic liver together with modern imaging modalities have increasingly improved the diagnostic of small sub-clinical HCC giving the benefit of curative treatment strategies. Ultrasonography is the recommended tool for surveillance of cirrhotic patients as well as for follow-up imaging in patients with nodules up to 1 cm, but cannot be recommended as the sole diagnostic imaging technique for tumors larger than 1 cm in size. Due to the large number of false negatives after biopsy of HCC up to 2 cm, other imaging modalities are necessary. HCC presenting at contrast enhanced computer tomography (CECT) and dynamic magnet resonance imaging (MRI) reveals a specific imaging pattern with enhancement at arterial phase, followed by a wash-out at more delayed phases. Furthermore, CT or MRI is needed for staging of patients with diagnosed HCC. In atypical lesions, biopsy should be performed, although biopsy results are inconsistent with up to 30% due to false-negative results, mostly due to sampling errors.

Early diagnosis and best treatment strategies are the sole option for a long-term survival of patients with liver cirrhosis and HCC.

Prof. Dr. Philippe L. Pereira
Guest Editor

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Keywords

  • HCC
  • epidemiology
  • surveillance – cirrhotic liver
  • pathology – HCC
  • ultrasonography
  • contrast-enhanced ultrasonography
  • biopsy – HCC
  • computer tomography
  • magnet resonance imaging

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Published Papers (8 papers)

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Research

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9 pages, 2417 KiB  
Article
Quantitative Assessment of Tissue Perfusion in Hepatocellular Carcinoma Using Perflubutane Dynamic Contrast-Enhanced Ultrasonography: A Preliminary Study
by Naoki Ohno, Tosiaki Miyati, Makiko Yamashita and Mayu Narikawa
Diagnostics 2015, 5(2), 210-218; https://doi.org/10.3390/diagnostics5020210 - 20 May 2015
Cited by 7 | Viewed by 6060
Abstract
Our purpose in this study was to assess the relationship between contrast signal intensity (CI) and concentration of perflubutane microbubbles in a phantom experiment, and to examine the feasibility of this technique for quantitative analysis of vascularity in hepatocellular carcinoma (HCC). Microbubble solutions [...] Read more.
Our purpose in this study was to assess the relationship between contrast signal intensity (CI) and concentration of perflubutane microbubbles in a phantom experiment, and to examine the feasibility of this technique for quantitative analysis of vascularity in hepatocellular carcinoma (HCC). Microbubble solutions of the perflubutane contrast agent were prepared by mixing with purified water. We examined the relationship between CI in dB units and the concentration. Moreover, seven HCC patients were examined using real-time dynamic contrast imaging. The perfusion index was calculated from time-intensity curves generated for both HCC and surrounding liver parenchyma. We observed a linear relationship between the CIdB and the concentration in the phantom study and a higher perfusion index in the HCC lesions relative to the surrounding liver parenchyma. Dynamic contrast-enhanced ultrasonography with perflubutane microbubbles, which exhibit linear and temporally stable characteristics under continuous ultrasound exposure, allows the collection of quantitative hemodynamic information regarding HCC. Full article
(This article belongs to the Special Issue Diagnosis of Hepatocellular Carcinoma)
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11 pages, 2342 KiB  
Article
Chronic Liver Disease and the Detection of Hepatocellular Carcinoma by [18F]fluorocholine PET/CT
by Sandi A. Kwee, Linda L. Wong, Brenda Y. Hernandez, Owen T.M. Chan, Miles M. Sato and Naoky Tsai
Diagnostics 2015, 5(2), 189-199; https://doi.org/10.3390/diagnostics5020189 - 19 May 2015
Cited by 13 | Viewed by 7729
Abstract
Positron emission tomography (PET) using the radiopharmaceutical tracer fluorine-18 fluorocholine (FCh) can elucidate tumors based on differences in choline phospholipid metabolism between tumor and surrounding tissue. The feasibility of detecting hepatocellular carcinoma (HCC) using FCh PET has been shown despite constitutively high parenchymal [...] Read more.
Positron emission tomography (PET) using the radiopharmaceutical tracer fluorine-18 fluorocholine (FCh) can elucidate tumors based on differences in choline phospholipid metabolism between tumor and surrounding tissue. The feasibility of detecting hepatocellular carcinoma (HCC) using FCh PET has been shown despite constitutively high parenchymal choline metabolism in the liver. Since HCC frequently develops in the setting of chronic liver disease, we comparatively evaluated FCh PET/CT between cirrhotic and non-cirrhotic patients with HCC to investigate the effects of hepatic dysfunction on tumor detection and the tumor-to-background ratio (TBR) of FCh uptake. FCh PET/CT was performed prospectively in 22 consecutive patients with HCC (7 newly diagnosed, 15 previously treated). Of these 22 patients, 14 were cirrhotic and 8 non-cirrhotic. Standardized uptake value (SUV) measurements were obtained by region of interest analysis of the PET images. Tumor FCh uptake and the TBR were compared between cirrhotic and non-cirrhotic patients. Liver lesions were confirmed to be HCC by biopsy in 10 patients and by Barcelona criteria in 4 patients. There was correspondingly increased liver tumor FCh uptake in 13/14 of those patients, and iso-intense tumor FCh uptake (TBR 0.94) in one non-cirrhotic patient with newly diagnosed HCC. FCh PET/CT also showed metastatic disease without local tumor recurrence in 2 previously treated patients, and was negative in 6 treated patients without tumor recurrence by radiographic and clinical follow-up. Tumor maximum SUV ranged from 6.4 to 15.3 (mean 12.1) and liver TBR ranged from 0.94 to 2.1 (mean 1.6), with no significant differences between cirrhotic and non-cirrhotic patients (SUVmax 11.9 vs. 12.2, p = 0.83; TBR 1.71 vs. 1.51, p = 0.29). Liver parenchyma mean SUV was significantly lower in cirrhotic patients (6.4 vs. 8.7, p < 0.05). This pilot study supports the general feasibility of HCC detection by FCh PET/CT. However, a broad range of tumor FCh uptake was observed, and lower liver parenchymal uptake of FCh was noted in cirrhotic patients as compared to non-cirrhotic patients. Incorporating tissue profiling into future liver imaging trials of FCh PET may help determine the molecular basis of the observed variations in tumor and hepatic FCh uptake. Full article
(This article belongs to the Special Issue Diagnosis of Hepatocellular Carcinoma)
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Review

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5 pages, 173 KiB  
Review
Surveillance for Hepatocellular Carcinoma in Patients with NASH
by Philippe Kolly and Jean-François Dufour
Diagnostics 2016, 6(2), 22; https://doi.org/10.3390/diagnostics6020022 - 7 Jun 2016
Cited by 33 | Viewed by 6544
Abstract
European and American guidelines recommend surveillance for hepatocellular carcinoma (HCC) by performing ultrasonography on a six-month basis on an at risk population, defined by presence of cirrhosis. HCC, due to non-alcoholic steatohepatitis (NASH), is rising. Patients with NASH have a high risk of [...] Read more.
European and American guidelines recommend surveillance for hepatocellular carcinoma (HCC) by performing ultrasonography on a six-month basis on an at risk population, defined by presence of cirrhosis. HCC, due to non-alcoholic steatohepatitis (NASH), is rising. Patients with NASH have a high risk of developing HCC and, therefore, have to be enrolled in a screening program. One of the challenges with NASH-induced HCC is that half of the cases arise in non-cirrhotic patients. There is a need to identify those patients in order to screen them for HCC. The obesity of these patients is another challenge, it makes ultrasound screening more difficult. Other radiological methods, such as computer tomography (CT) scans or magnetic resonance imaging (MRI), are available, but the surveillance program would no longer be cost-effective. There is a need to prospectively acquire information on cohorts of patients with NASH in order to improve the tools we have to diagnose early tumors in these patients. Full article
(This article belongs to the Special Issue Diagnosis of Hepatocellular Carcinoma)
7 pages, 1807 KiB  
Review
Computed Tomography and Ultrasounds for the Follow-up of Hepatocellular Carcinoma Ablation: What You Need to Know
by Alexios Kelekis and Dimitrios Filippiadis
Diagnostics 2016, 6(1), 9; https://doi.org/10.3390/diagnostics6010009 - 4 Feb 2016
Cited by 4 | Viewed by 6511
Abstract
Image-guided tumor ablation provides curative treatment in properly selected patients or appropriate therapeutic options whenever surgical techniques are precluded. Tumor response assessment post ablation is important in determining treatment success and future therapy. Accurate interpretation of post-ablation imaging findings is crucial for therapeutic [...] Read more.
Image-guided tumor ablation provides curative treatment in properly selected patients or appropriate therapeutic options whenever surgical techniques are precluded. Tumor response assessment post ablation is important in determining treatment success and future therapy. Accurate interpretation of post-ablation imaging findings is crucial for therapeutic and follow-up strategies. Computed Tomography (CT) and Ultrasound (US) play important roles in patients’ follow-up post liver thermal ablation therapies. Contrast-enhanced ultrasound (CEUS) can provide valuable information on the ablation effects faster and at a lower cost than computed tomography or magnetic resonance imaging. However, a disadvantage is that the technique cannot examine total liver parenchyma for disease progression as CT and Magnetic Resonance (MR) imaging can. Follow-up strategies for assessment of tumor response includes contrast enhanced multiphasic (non-contrast, arterial, portal, delayed phases) imaging with Computed Tomography at three, six, and 12 months post ablation session and annually ever since in order to prove sustained effectiveness of the ablation or detect progression. Full article
(This article belongs to the Special Issue Diagnosis of Hepatocellular Carcinoma)
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18 pages, 8267 KiB  
Review
The Role of Diffusion-Weighted Imaging (DWI) in Locoregional Therapy Outcome Prediction and Response Assessment for Hepatocellular Carcinoma (HCC): The New Era of Functional Imaging Biomarkers
by Johannes M. Ludwig, Juan C. Camacho, Nima Kokabi, Minzhi Xing and Hyun S. Kim
Diagnostics 2015, 5(4), 546-563; https://doi.org/10.3390/diagnostics5040546 - 30 Nov 2015
Cited by 24 | Viewed by 9709
Abstract
Reliable response criteria are critical for the evaluation of therapeutic response in hepatocellular carcinoma (HCC). Current response assessment is mainly based on: (1) changes in size, which is at times unreliable and lag behind the result of therapy; and (2) contrast enhancement, which [...] Read more.
Reliable response criteria are critical for the evaluation of therapeutic response in hepatocellular carcinoma (HCC). Current response assessment is mainly based on: (1) changes in size, which is at times unreliable and lag behind the result of therapy; and (2) contrast enhancement, which can be difficult to quantify in the presence of benign post-procedural changes and in tumors presenting with a heterogeneous pattern of enhancement. Given these challenges, functional magnetic resonance imaging (MRI) techniques, such as diffusion-weighted imaging (DWI) have been recently investigated, aiding specificity to locoregional therapy response assessment and outcome prediction. Briefly, DWI quantifies diffusion of water occurring naturally at a cellular level (Brownian movement), which is restricted in multiple neoplasms because of high cellularity. Disruption of cellular integrity secondary to therapy results in increased water diffusion across the injured membranes. This review will provide an overview of the current literature on DWI therapy response assessment and outcome prediction in HCC following treatment with locoregional therapies. Full article
(This article belongs to the Special Issue Diagnosis of Hepatocellular Carcinoma)
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33 pages, 3836 KiB  
Review
Imaging of HCC—Current State of the Art
by Christina Schraml, Sascha Kaufmann, Hansjoerg Rempp, Roland Syha, Dominik Ketelsen, Mike Notohamiprodjo and Konstantin Nikolaou
Diagnostics 2015, 5(4), 513-545; https://doi.org/10.3390/diagnostics5040513 - 27 Nov 2015
Cited by 37 | Viewed by 15219
Abstract
Early diagnosis of hepatocellular carcinoma (HCC) is crucial for optimizing treatment outcome. Ongoing advances are being made in imaging of HCC regarding detection, grading, staging, and also treatment monitoring. This review gives an overview of the current international guidelines for diagnosing HCC and [...] Read more.
Early diagnosis of hepatocellular carcinoma (HCC) is crucial for optimizing treatment outcome. Ongoing advances are being made in imaging of HCC regarding detection, grading, staging, and also treatment monitoring. This review gives an overview of the current international guidelines for diagnosing HCC and their discrepancies as well as critically summarizes the role of magnetic resonance imaging (MRI) and computed tomography (CT) techniques for imaging in HCC. The diagnostic performance of MRI with nonspecific and hepatobililiary contrast agents and the role of functional imaging with diffusion-weighted imaging will be discussed. On the other hand, CT as a fast, cheap and easily accessible imaging modality plays a major role in the clinical routine work-up of HCC. Technical advances in CT, such as dual energy CT and volume perfusion CT, are currently being explored for improving detection, characterization and staging of HCC with promising results. Cone beam CT can provide a three-dimensional analysis of the liver with tumor and vessel characterization comparable to cross-sectional imaging so that this technique is gaining an increasing role in the peri-procedural imaging of HCC treated with interventional techniques. Full article
(This article belongs to the Special Issue Diagnosis of Hepatocellular Carcinoma)
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7 pages, 685 KiB  
Review
Early Detection of Hepatocellular Carcinoma: How to Screen and Follow up Patients with Liver Cirrhosis According to the GERMAN S3 Guideline?
by Ruben R. Plentz and Nisar P. Malek
Diagnostics 2015, 5(4), 497-503; https://doi.org/10.3390/diagnostics5040497 - 25 Nov 2015
Cited by 9 | Viewed by 6068
Abstract
Hepatocellular carcinoma (HCC) is frequently detected in pre-existing liver cirrhosis, but can also develop without such pre-conditions. There is an increasing trend of HCC incidence worldwide. In patients with liver cirrhosis, HCC has become the leading cause of death. At diagnosis the tumor [...] Read more.
Hepatocellular carcinoma (HCC) is frequently detected in pre-existing liver cirrhosis, but can also develop without such pre-conditions. There is an increasing trend of HCC incidence worldwide. In patients with liver cirrhosis, HCC has become the leading cause of death. At diagnosis the tumor has very often reached an advanced stage and curative treatment options are missing. Thus, early diagnosis would help the patient and prevent increasing healthcare costs. In our review we will summarize the recommendations of the German S3 guideline for the early diagnosis of HCC and will discuss the current literature in this context. The reader will learn which diagnostic tools are available and in what order they can be usefully applied. Surveillance should be done with ultrasound by a skilled examiner, additional imaging at best with state-of-the-art dynamic magnetic resonance. Full article
(This article belongs to the Special Issue Diagnosis of Hepatocellular Carcinoma)
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Other

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12 pages, 2108 KiB  
Brief Report
Hepatocellular Carcinoma, Fibrolamellar Variant: Diagnostic Pathologic Criteria and Molecular Pathology Update. A Primer
by Consolato M. Sergi
Diagnostics 2016, 6(1), 3; https://doi.org/10.3390/diagnostics6010003 - 30 Dec 2015
Cited by 18 | Viewed by 11747
Abstract
Fibrolamellar hepatocellular carcinoma (FL-HCC) is generally a fairly rare event in routine pathology practice. This variant of hepatocellular carcinoma (HCC) is peculiarly intriguing and,in addition, poorly understood. Young people or children are often the target individuals with this type of cancer. Previously, I [...] Read more.
Fibrolamellar hepatocellular carcinoma (FL-HCC) is generally a fairly rare event in routine pathology practice. This variant of hepatocellular carcinoma (HCC) is peculiarly intriguing and,in addition, poorly understood. Young people or children are often the target individuals with this type of cancer. Previously, I highlighted some pathology aspects of FL-HCC, but in this review, the distinctive clinico-pathologic features of FL-HCC and the diagnostic pathologic criteria of FL-HCC are fractionally reviewed and expanded upon. Further, molecular genetics update data with reference to this specific tumor are particularly highlighted as a primer for general pathologists and pediatric histopathologists. FL-HCC may present with metastases, and regional lymph nodes may be sites of metastatic spread. However, peritoneal and pulmonary metastatic foci have also been reported. To the best of our knowledge, FL-HCC was initially considered having an indolent course, but survival outcomes have recently been updated reconsidering the prognosis of this tumor. Patients seem to respond well to surgical resection, but recurrences are common. Thus, alternative therapies, such as chemotherapy and radiation, are ongoing. Overall, it seems that this aspect has not been well-studied for this variant of HCC and should be considered as target for future clinical trials. Remarkably, FL-HCC data seem to point to a liver neoplasm of uncertain origin and unveiled outcome. A functional chimeric transcript incorporating DNAJB1 and PRKACA was recently added to FL-HCC. This sensational result may give remarkable insights into the understanding of this rare disease and potentially provide the basis for its specific diagnostic marker. Detection of DNAJB1-PRKACA seems to be, indeed, a very sensitive and specific finding in supporting the diagnosis of FL-HCC. In a quite diffuse opinion, prognosis of this tumor should be reconsidered following the potentially mandatory application of new molecular biological tools. Full article
(This article belongs to the Special Issue Diagnosis of Hepatocellular Carcinoma)
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