Noninvasive Diagnosis of Hepatocellular Carcinoma on Sonazoid-Enhanced US: Value of the Kupffer Phase

The aim of this study was to compare the diagnostic performance of Contrast-Enhanced US Liver Imaging Reporting and Data System (CEUS LI-RADS) version 2017, which includes portal- and late-phase washout as a major imaging feature, with that of modified CEUS LI-RADS, which includes Kupffer-phase findings as a major imaging feature. Participants at risk of hepatocellular carcinoma (HCC) with treatment-naïve hepatic lesions (≥1 cm) were recruited and underwent Sonazoid-enhanced US. Arterial phase hyperenhancement (APHE), washout time, and echogenicity in the Kupffer phase were evaluated using both criteria. The diagnostic performance of both criteria was analyzed using the McNemar test. The evaluation was performed on 102 participants with 102 lesions (HCCs (n = 52), non-HCC malignancies (n = 36), and benign (n = 14)). Among 52 HCCs, non-rim APHE was observed in 92.3% (48 of 52). By 5 min, 73.1% (38 of 52) of HCCs showed mild washout, while by 10 min or in the Kupffer phase, 90.4% (47 of 52) of HCCs showed hypoenhancement. The sensitivity (67.3%; 35 of 52; 95% CI: 52.9%, 79.7%) of modified CEUS LI-RADS criteria was higher than that of CEUS LI-RADS criteria (51.9%; 27 of 52; 95% CI: 37.6%, 66.0%) (p = 0.0047). In conclusion, non-rim APHE with hypoenhancement in the Kupffer phase on Sonazoid-enhanced US is a feasible criterion for diagnosing HCC.

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Interobserver Agreement for Contrast-Enhanced Ultrasound (CEUS)-Based Standardized Algorithms for the Diagnosis of Hepatocellular Carcinoma in High-Risk Patients

Ultraschall in der Medizin - European Journal of Ultrasound ◽

10.1055/a-0612-7887 ◽

2018 ◽

Vol 39 (06) ◽

pp. 667-674 ◽

Cited By ~ 10

Author(s):

Barbara Schellhaas ◽

Lukas Pfeifer ◽

Christian Kielisch ◽

Ruediger Goertz ◽

Markus Neurath ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

High Risk ◽

Interobserver Agreement ◽

Late Phase ◽

Arterial Phase ◽

Liver Imaging ◽

Contrast Enhanced Ultrasound ◽

High Risk Patients ◽

Contrast Enhanced ◽

Risk Patients

Abstract Objectives This pilot study aimed at assessing interobserver agreement with two contrast-enhanced ultrasound (CEUS) algorithms for the diagnosis of hepatocellular carcinoma (HCC) in high-risk patients. Methods Focal liver lesions in 55 high-risk patients were assessed independently by three blinded observers with two standardized CEUS algorithms: ESCULAP (Erlanger Synopsis of Contrast-Enhanced Ultrasound for Liver Lesion Assessment in Patients at risk) and ACR-CEUS-LI-RADSv.2016 (American College of Radiology CEUS-Liver Imaging Reporting and Data System). Lesions were categorized according to size and ultrasound contrast enhancement in the arterial, portal-venous and late phase. Interobserver agreement for assessment of enhancement pattern and categorization was compared between both CEUS algorithms. Additionally, diagnostic accuracy for the definitive diagnosis of HCC was compared. Histology and/or CE-MRI and follow-up served as reference standards. Results 55 patients were included in the study (male/female, 44/ 11; mean age: 65.9 years). 90.9 % had cirrhosis. Histological findings were available in 39/55 lesions (70.9 %). Reference standard of the 55 lesions revealed 48 HCCs, 2 intrahepatic cholangiocellular carcinomas (ICCs), and 5 non-HCC-non-ICC lesions. Interobserver agreement was moderate to substantial for arterial phase hyperenhancement (ĸ = 0.53 – 0.67), and fair to moderate for contrast washout in the portal-venous or late phase (ĸ = 0.33 – 0.53). Concerning the CEUS-based algorithms, the interreader agreement was substantial for the ESCULAP category (ĸ = 0.64 – 0.68) and fair for the CEUS-LI-RADS® category (ĸ = 0.3 – 0.39). Disagreement between observers was mostly due to different perception of washout. Conclusion Interobserver agreement is better for ESCULAP than for CEUS-LI-RADS®. This is mostly due to the fact that perception of contrast washout varies between different observers. However, interobserver agreement is good for arterial phase hyperenhancement, which is the key diagnostic feature for the diagnosis of HCC with CEUS in the cirrhotic liver.

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Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System in Diagnosing Hepatocellular Carcinoma: Diagnostic Performance and Interobserver Agreement

Ultraschall in der Medizin - European Journal of Ultrasound ◽

10.1055/a-1168-6321 ◽

2020 ◽

Author(s):

Hang Zhou ◽

Chao Zhang ◽

Linyao Du ◽

Jiapeng Jiang ◽

Qing Zhao ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

High Risk ◽

Diagnostic Performance ◽

Data System ◽

Liver Imaging ◽

Contrast Enhanced Ultrasound ◽

High Risk Patients ◽

Contrast Enhanced ◽

Sensitivity Range ◽

Risk Patients

Abstract Objectives To determine the diagnostic performance and inter-reader agreement of the contrast-enhanced ultrasound liver imaging reporting and data system (CEUS-LI-RADS) for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. Methods In this prospective study, CEUS-LI-RADS categories (LR-5 for predicting HCC) were assigned by six blinded readers and compared to the definitive HCC diagnosis in patients with liver cirrhosis per the 2017 China Liver Cancer Guidelines (CLCG). CEUS features were recorded in 96 patients with 96 histology-proven lesions. The diagnostic performance of LR-5 was described by the sensitivity, specificity and accuracy. Multi-reader agreement was assessed by using intraclass correlation coefficients (ICC). Results In cirrhotic patients, the specificity of LR-5 (range: 92.7–100.0 %) was statistically higher than that of CLCG for each reader (range: 28.6–64.3 %). However, the sensitivity (range: 38.6–63.6 %) and accuracy (range: 53.4–70.7 %) were statistically lower in CEUS-LIRADS than in CLCG (sensitivity range: 88.6–100.0 %; accuracy range: 77.6–86.2 %). Only fair to moderate inter-reader agreement was achieved for the CEUS-LI-RADS category (ICC = 0.595) and washout appearance (ICC range: 0.338 to 0.555). Neither nodule-in-nodule nor mosaic architecture was observed more often in HCC (all P > 0.05), with poor inter-reader consistency for both (both ICC < 0.20). Conclusion CEUS-LI-RADS category 5 has a high specificity but a low accuracy for identifying HCC in high-risk patients. Inter-reader agreement is not satisfactory concerning CEUS-LIRADS category and washout appearance. Moreover, the clinical value of ancillary features favoring HCC is quite limited.

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Usefulness of Modified CEUS LI-RADS for the Diagnosis of Hepatocellular Carcinoma Using Sonazoid

Diagnostics ◽

10.3390/diagnostics10100828 ◽

2020 ◽

Vol 10 (10) ◽

pp. 828

Author(s):

Katsutoshi Sugimoto ◽

Tatsuya Kakegawa ◽

Hiroshi Takahashi ◽

Yusuke Tomita ◽

Masakazu Abe ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Predictive Value ◽

Arterial Phase ◽

Liver Imaging ◽

Adrenal Rest Tumor ◽

Contrast Enhanced ◽

Rim Enhancement ◽

Diagnostic Usefulness ◽

Adrenal Rest ◽

Sensitivity Specificity

The Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS) was introduced for classifying suspected hepatocellular carcinoma (HCC). However, it cannot be applied to Sonazoid. We assessed the diagnostic usefulness of a modified CEUS LI-RADS for HCC and non-HCC malignancies based on sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Patients with chronic liver disease at risk for HCC were evaluated retrospectively. Nodules ≥1 cm with arterial phase hyperenhancement, no early washout (within 60 s), and contrast defects in the Kupffer phase were classified as LR-5. Nodules showing early washout, contrast defects in the Kupffer phase, and/or rim enhancement were classified as LR-M. A total of 104 nodules in 104 patients (median age: 70.0 years; interquartile range: 54.5–78.0 years; 74 men) were evaluated. The 48 (46.2%) LR-5 lesions included 45 HCCs, 2 high-flow hemangiomas, and 1 adrenal rest tumor. The PPV of LR-5 for HCC was 93.8% (95% confidence interval (CI): 82.8–98.7%). The 22 (21.2%) LR-M lesions included 16 non-HCC malignancies and 6 HCCs. The PPV of LR-M for non-HCC malignancies, including six intrahepatic cholangiocarcinomas, was 100% (95% CI: 69.8–100%). In conclusion, in the modified CEUS LI-RADS for Sonazoid, LR-5 and LR-M are good predictors of HCC and non-HCC malignancies, respectively.

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Gadoxetic acid-enhanced MRI of hepatocellular carcinoma: Diagnostic performance of category-adjusted LR-5 using modified criteria

PLoS ONE ◽

10.1371/journal.pone.0242344 ◽

2020 ◽

Vol 15 (11) ◽

pp. e0242344

Author(s):

Jae Hyon Park ◽

Yong Eun Chung ◽

Nieun Seo ◽

Jin-Young Choi ◽

Mi-Suk Park ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Diagnostic Performance ◽

Arterial Phase ◽

Liver Imaging ◽

Gadoxetate Disodium ◽

Resonance Imaging ◽

Feature Based ◽

Increased Sensitivity ◽

Transitional Phase ◽

Ancillary Features

The Liver Imaging Reporting and Data System (LI-RADS) is widely adopted for the noninvasive diagnosis of hepatocellular carcinoma (HCC). Herein, possible strategies to improve the diagnostic performance of LR-5 without reducing specificity for HCC were investigated. This retrospective study included 792 patients who underwent gadoxetate disodium-enhanced magnetic resonance imaging. Hepatic observations were categorized according to LI-RADS v2018 and categories were readjusted by upgrading LR4 to LR5 using ancillary features, arterial phase hyperenhancement (APHE) interpreted with subtraction images, indication of no washout when APHE was absent, extension of washout to the transitional phase, and subthreshold growth as a major feature. Based on LI-RADS v2018, LR-5 showed a sensitivity of 71.9% and a specificity of 97.9% for the diagnosis of HCC. Category-readjusted LR-5 after upgrading LR-4 to LR-5 using ancillary features favoring HCC in particular, subthreshold growth as a major feature, extending washout to transitional phase and APHE interpreted using subtraction images showed significantly increased sensitivity (P<0.001) without decreased specificity (Ps>0.05). The sensitivity of LR-5 can be improved without loss of specificity via category readjustment using AFs favoring HCC in particular, subthreshold growth as a major feature, extending washout to transitional phase and APHE interpreted with subtraction images.

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Size measurements of hepatocellular carcinoma: comparisons between contrast and two-dimensional ultrasound

10.21203/rs.3.rs-38690/v1 ◽

2020 ◽

Author(s):

Fei Chen ◽

Fei Wang ◽

Mei Zhu ◽

Si Sun ◽

Zheng Liu

Keyword(s):

Hepatocellular Carcinoma ◽

Late Phase ◽

Size Difference ◽

Arterial Phase ◽

Two Dimensional ◽

Test Results ◽

Contrast Enhanced ◽

2D Imaging ◽

The Mean ◽

Longitudinal Diameter

Abstract Background Ultrasound (US) imaging is known to underestimate tumor size in clinical. This study is aimed to compare the size measurements of hepatocellular carcinoma (HCC) in three US imaging modalities, i.e. two-dimensional (2D) imaging, the arterial phase (AP) and the late phase (LP) imaging of contrast-enhanced US (CEUS). Methods Fifty-eight clinically proved HCC patients were included. The 2D and CEUS imaging were performed with Siemens S2000, Philips iu22 and BioSound Twice. 2.5 mL of SonoVue® was injected for every CEUS performance. Two physicians measured the maximal longitudinal and the transverse diameters of the tumors in 2D, the AP and the LP of CEUS from one image section. The three measurements were compared by paired t test. Results The mean longitudinal diameter of HCC appeared to be maximal in the AP (4.73 ± 2.04 cm) of CEUS and minimal in the LP (3.98 ± 1.99 cm) of CEUS. The 2D diameter (4.26 ± 2.07 cm) was in the middle between two CEUS measurements. There were significant differences between any two measurements. Conclusion There is size difference between the three kinds of HCC measurement. It appeared to be maximal in the AP of CEUS and minimal in the LP. The 2D diameter was in the middle.

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Size measurements of hepatocellular carcinoma: comparisons between contrast and two-dimensional ultrasound

10.21203/rs.3.rs-38690/v2 ◽

2020 ◽

Author(s):

Fei Chen ◽

Fei Wang ◽

Si Sun ◽

Mei Zhu ◽

Zheng Liu

Keyword(s):

Hepatocellular Carcinoma ◽

Late Phase ◽

Size Difference ◽

Arterial Phase ◽

Two Dimensional ◽

Test Results ◽

Contrast Enhanced ◽

2D Imaging ◽

The Mean ◽

Longitudinal Diameter

Abstract Background Ultrasound (US) imaging is known to underestimate tumor size in clinical. This study is aimed to compare the size measurements of hepatocellular carcinoma (HCC) in three US imaging modalities, i.e. two-dimensional (2D) imaging, the arterial phase (AP) and the late phase (LP) imaging of contrast-enhanced US (CEUS). Methods Fifty-eight clinically proved HCC patients were included. The 2D and CEUS imaging were performed with Siemens S2000, Philips iu22 and BioSound Twice. 2.5 mL of SonoVue® was injected for every CEUS performance. Two physicians measured the maximal longitudinal and the transverse diameters of the tumors in 2D, the AP and the LP of CEUS from one image section. The three measurements were compared by paired t test. Results The mean longitudinal diameter of HCC appeared to be maximal in the AP (4.73±2.04 cm) of CEUS and minimal in the LP (3.98±1.99 cm) of CEUS. The 2D diameter (4.26±2.07 cm) was in the middle between two CEUS measurements. There were significant differences between any two measurements. Conclusion There is size difference between the three kinds of HCC measurement. It appeared to be maximal in the AP of CEUS and minimal in the LP. The 2D diameter was in the middle.

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Size measurements of hepatocellular carcinoma: comparisons between contrast and two-dimensional ultrasound

BMC Gastroenterology ◽

10.1186/s12876-020-01535-1 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Fei Chen ◽

Fei Wang ◽

Si Sun ◽

Mei Zhu ◽

Zheng Liu

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Size ◽

Late Phase ◽

Size Difference ◽

Arterial Phase ◽

Two Dimensional ◽

Contrast Enhanced ◽

2D Imaging ◽

The Mean ◽

Longitudinal Diameter

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Alteration of contrast enhanced ultrasound (CEUS) of hepatocellular carcinoma in patients with cirrhosis and transjugular intrahepatic portosystemic shunt (TIPS)

Scientific Reports ◽

10.1038/s41598-020-77801-9 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Johannes Chang ◽

Alexia Dumitrache ◽

Nina Böhling ◽

Jasmin Abu-Omar ◽

Carsten Meyer ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Transjugular Intrahepatic Portosystemic Shunt ◽

Gold Standard ◽

Diagnostic Performance ◽

Portosystemic Shunt ◽

Arterial Phase ◽

Liver Lesions ◽

Contrast Enhanced Ultrasound ◽

Contrast Enhanced ◽

Intrahepatic Portosystemic Shunt

AbstractTransjugular intrahepatic portosystemic shunt (TIPS) can treat portal hypertensive complications and modifies hepatic hemodynamics. Modification of liver perfusion can alter contrast enhancement dynamics of liver nodules. This study investigated the diagnostic performance of contrast-enhanced ultrasound (CEUS) to diagnose hepatocellular carcinoma (HCC) in cirrhosis with TIPS. In this prospective monocentric observational study, CEUS was used to characterize focal liver lesions in patients at risk for HCC with and without TIPS. Times of arterial phase hyperenhancement (APHE) und washout were quantified. Perfusion-index (PI) and resistance-index (RI) of hepatic artery and portal venous flow parameters were measured via doppler ultrasonography. Diagnostic gold standard was MRI/CT or histology. This study included 49 liver lesions [23 TIPS (11 HCC), 26 no TIPS (15 HCC)]. 26 were diagnosed as HCC by gold standard. Sensitivity and specificity of CEUS to diagnose HCC with and without TIPS were 93.3% and 100% vs. 90.9% and 93.3%, respectively. APHE appeared significantly earlier in patients with TIPS compared to patients without TIPS. TIPS significantly accentuates APHE of HCC in CEUS. CEUS has good diagnostic performance for diagnosis of HCC in patients with TIPS.

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Size measurements of hepatocellular carcinoma: comparisons between contrast and two-dimensional ultrasound

10.21203/rs.3.rs-38690/v3 ◽

2020 ◽

Author(s):

Fei Chen ◽

Fei Wang ◽

Si Sun ◽

Mei Zhu ◽

Zheng Liu

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Size ◽

Late Phase ◽

Size Difference ◽

Arterial Phase ◽

Two Dimensional ◽

Contrast Enhanced ◽

2D Imaging ◽

The Mean ◽

Longitudinal Diameter

Abstract Background: Ultrasound (US) imaging is known to underestimate tumor size in clinical. This study is aimed to compare the size measurements of hepatocellular carcinoma (HCC) in three US imaging modalities, i.e. two-dimensional (2D) imaging, the arterial phase (AP) and the late phase (LP) imaging of contrast-enhanced US (CEUS).Methods: Fifty-eight clinically proved HCC patients were included. The 2D and CEUS imaging were performed with Siemens S2000, Philips iu22 and BioSound Twice. 2.5 mL of SonoVue® was injected for every CEUS performance. Two physicians measured the maximal longitudinal and the transverse diameters of the tumors in 2D, the AP and the LP of CEUS from one image section. The three measurements were compared by paired t test.Results: The mean longitudinal diameter of HCC appeared to be maximal in the AP (4.73±2.04 cm) of CEUS and minimal in the LP (3.98±1.99 cm) of CEUS. The 2D diameter (4.26±2.07 cm) was in the middle between two CEUS measurements. There were significant differences between any two measurements.Conclusion: There is size difference between the three kinds of HCC measurement. It appeared to be maximal in the AP of CEUS and minimal in the LP. The 2D diameter was in the middle.

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Contrast-Enhanced Ultrasound Findings of Hepatocellular Carcinoma With Neuroendocrine Carcinoma: A Case Report

Frontiers in Medicine ◽

10.3389/fmed.2021.602346 ◽

2021 ◽

Vol 8 ◽

Author(s):

Hong Wang ◽

Dan Yang ◽

Zhenru Wu ◽

Yan Luo ◽

Wenwu Ling

Keyword(s):

Hepatocellular Carcinoma ◽

Case Report ◽

Neuroendocrine Carcinoma ◽

Late Phase ◽

Focal Liver Lesion ◽

Arterial Phase ◽

Phase Imaging ◽

Contrast Enhanced Ultrasound ◽

Imaging Characteristics ◽

Contrast Enhanced

Hepatocellular carcinoma (HCC) with the concurrent occurrence of primary hepatic neuroendocrine carcinoma (NEC) of the liver is extremely rare. Preoperative diagnosis of HCC combined with NEC is very difficult. Here, we presented a case report of HCC combined with NEC. A 33-year-old male was admitted to our hospital due to focal liver lesion. To further the diagnosis, he received laboratory tests, conventional ultrasound, contrast-enhanced ultrasound (CEUS), and magnetic resonance imaging (MRI). Grayscale ultrasound showed a hypoechoic nodule with peripheral hypoechoic halo and central small patches of anechoic area in the hepatic segment VI, and the liver background was cirrhosis. In the CEUS, the solid component of the nodule was rapidly homogeneous hyper-enhancement in the arterial phase. Then, the enhancement of the nodule was washed out slowly and gradually; the nodule presented heterogeneously mild enhancement in the portal phase, and slight hypo-enhancement was showed in the late phase. The hypo-enhanced area was mainly located in the surrounding space. Meanwhile, there was a small piece of non-enhanced area within the lesion center in the whole three-phase imaging. MRI showed a lobular contoured mass in segment VI. The patient underwent middle liver resection, splenectomy, and cholecystectomy. The pathological diagnosis was a HCC with NEC. At the time of the preparation of this manuscript, the patient has been alive without recurrence or distant metastases for 6 months since the surgery. We mainly focus on the ultrasound imaging characteristics, especially its enhancement manifestations on CEUS. In this report, since this article is a case report, which is based on the clinical information of the patient and does not involve the patient's privacy, informed consent is not necessary. In addition, the patient agreed to publish the case. To the best of our knowledge, this report is the first to describe the CEUS patterns of the HCC combined with NEC. Herein, we report a case that provides novel insights that will improve clinicians' awareness of the clinical and ultrasound manifestations of this mixed tumor, resulting in improved diagnosis, treatment, and outcomes.

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