Contrast-Enhanced Ultrasound Patterns for the Non-invasive Diagnosis of Hepatocellular Carcinoma: A Prospective Multicenter Study in Histologically Proven Liver Lesions in a Real-Life Setting Demonstrating the Benefit of Extended Late Phase Observation

Schellhaas, Barbara; Bernatik, T.; Dirks, Klaus; Jesper, Daniel; Mauch, M.; Potthoff, Andrej; Zimmermann, Patrick; Strobel, D

doi:10.1016/j.ultrasmedbio.2021.07.010

Cited by 16 publications

(18 citation statements)

References 19 publications

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“…The design of the DEGUM CEUS HCC study has been described in detail recently [3][4]. Briefly, the study was conducted as a prospective multicentre study.…”

Section: Methodsmentioning

confidence: 99%

“…Most recently, we conducted a prospective multicentre study funded by the German Society for Ultrasound in Medicine (DEGUM) to assess the diagnostic accuracy of standardised CEUS for the noninvasive diagnosis of HCC in high-risk patients in a real-life setting [3][4]. Our results suggested that although arterial phase APHE can be considered the main characteristic feature of HCC in CEUS, some HCCs showed an atypical enhancement pattern with a lack of APHE.…”

Section: Introductionmentioning

confidence: 90%

“…Contrast-enhanced ultrasound (CEUS) was performed following a standardized protocol [3,4,6]. Examiners were instructed to apply a second contrast bolus with subsequent assessment of the late phase only if contrast enhancement was insufficient in the late phase.…”

Section: Standardized Contrast Enhanced Ultrasoundmentioning

confidence: 99%

“…Hepatocellular carcinoma (HCC) in high-risk patients can be diagnosed non-invasively using contrastenhanced ultrasound (CEUS), magnetic resonance imaging (MRI), or computed tomography (CT), if the typical enhancement pattern of arterial phase hyperenhancement (APHE) followed by contrast washout (WO) in the portal venous or late phase is present. Standardised CEUS algorithms such as CEUS LI-RADS (Contrast Enhanced UltraSound Liver Imaging Reporting And Data System) and ESCULAP (Erlanger Synopsis for Contrast-enhanced Ultrasound for Liver lesion Assessment in Patients at risk) allow a subtle classification of nodules using categories ranging from definitely benign nodules to definite HCC [1][2][3][4]. According to CEUS LI-RADS, non-invasive diagnosis of HCC in CEUS relies on a combination of APHE followed by contrast washout of mild degree with an onset no earlier than ≥ 60 seconds after contrast injection.…”

Section: Introductionmentioning

confidence: 99%

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HCCs lacking arterial phase hyperenhancement (APHE) on contrast-enhanced ultrasound (CEUS) – a diagnostic challenge. Findings from the prospective multicenter DEGUM CEUS HCC trial

et al. 2023

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Objectives Hepatocellular carcinoma (HCC) upon contrast-enhanced ultrasound (CEUS) typically shows arterial phase hyperenhancement (APHE), followed by late (> 60 seconds) and mild contrast washout (WO). Although APHE is considered as the hallmark of HCC, it can be absent in some HCCs. Thus, we explored which sonomorphological and histopathological features of HCC are associated with a lack of APHE upon CEUS. Methods Focal liver lesions in high-risk patients for HCC were assessed with CEUS following a standardised protocol in a prospective multi-centre real-life setting. CEUS patterns in HCC were assessed, and tumour and patient characteristics were compared for HCCs with and without APHE. Results 316 patients with HCC were recruited (cirrhosis, 76.9%). APHE occurred in 271/316 HCCs (85.8%). A lack of APHE was associated with portal vein thrombosis, tumour infiltration of the liver vessels (p<0.001), larger size, multilocularity, and higher depth location upon ultrasound (p<0.01). Histological grading did not differ between HCCs with and without APHE (p=0.39). Histopathological features of HCCs without APHE included cirrhotic stromal reaction, marked tumour cell steatosis and absence of the typical surrounding dilated sinusoidal vascular channels. Conclusion Correlation with histopathological findings support the fact that HCCs with a lack of APHE in CEUS are a heterogeneous group. The examiner has to be aware that HCCs with portal vein thrombosis or macro-invasion of the liver vessels may lack APHE. Ziele Hepatozelluläre Karzinome (HCCs) zeigen in der Kontrastmittelsonographie (CEUS) typischerweise ein arterielles Hyperenhancement (APHE) mit nachfolgend spätem (> 60 Sekunden), mildem Auswaschen (WO). Obwohl APHE das Hauptkriterium in der HCC-Diagnostik darstellt, fehlt dieses Merkmal bei einigen HCCs. Die vorliegende Arbeit sollte untersuchen, welche sonomorphologischen und histopathologischen Eigenschaften mit fehlendem APHE assoziiert sind. Methoden Fokale Leberläsionen bei HCC-Hochrisikopatienten wurden nach einem standardisierten CEUS-Protokoll in einem prospektiven multizentrischen Ansatz untersucht. Die CEUS-Muster der HCCs wurden analysiert und Tumor- und Patientencharakteristika für HCCs mit und ohne APHE verglichen. Ergebnisse 316 HCC-Patienten wurden eingeschlossen (76,9% Zirrhose). APHE fand sich bei 271/316 HCCs (85,8%). Fehlendes APHE war assoziiert mit Pfortaderthrombose, Tumorinfiltration in die Lebergefäße (p<0,001), größerem Tumordurchmesser, Multilokularität und größerer Tiefenlokalisation (p<0,01). Der histologische Differenzierungsgrad unterschied sich nicht zwischen HCCs mit und ohne APHE (p=0,39). Histologisch zeigten HCCs ohne APHE zirrhotische Stromareaktionen, ausgeprägte Tumorzellverfettung und ein Fehlen der typischen umgebenden erweiterten Sinusoide. Schlussfolgerungen Die Korrelation mit histopathologischen Merkmalen belegt, dass HCCs mit fehlendem APHE im CEUS eine heterogene Gruppe darstellen. Der Untersucher sollte sich bewusst machen, dass APHE bei HCCs mit Pfortaderthrombose oder Makrogefäßinvasion fehlen kann.

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“…The design of the DEGUM CEUS HCC study has been described in detail recently [3][4]. Briefly, the study was conducted as a prospective multicentre study.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 90%

Section: Standardized Contrast Enhanced Ultrasoundmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

HCCs lacking arterial phase hyperenhancement (APHE) on contrast-enhanced ultrasound (CEUS) – a diagnostic challenge. Findings from the prospective multicenter DEGUM CEUS HCC trial

et al. 2023

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“…The study design of the prospective multicentre Deutsche Gesellschaft für Ultraschall in der Medizin CEUS HCC (DEGUM CEUS HCC) study has been described in detail recently [3][4][5]. Briefly, high-risk patients for HCC according to national guidelines (chronic hepatitis B infection, chronic hepatitis C infection with advanced fibrosis, NASH and history of prior HCC [6]) with focal liver lesions were recruited prospectively in a real-life approach.…”

Section: Methodsmentioning

confidence: 99%

Contrast-enhanced ultrasound pattern of hepatocellular carcinoma in noncirrhotic liver – results from the prospective multicentre DEGUM CEUS HCC study

Schellhaas¹,

Jesper²,

Strobel³

2022

European Journal of Gastroenterology &Amp; Hepatology

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Objectives Contrast-enhanced ultrasound (CEUS) has a high diagnostic accuracy for the noninvasive diagnosis of hepatocellular carcinoma (HCC) in cirrhosis. However, as HCC in noncirrhosis becomes an emerging clinical concern, our study aimed to assess the diagnostic value of CEUS and the CEUS algorithms CEUS LI-RADS and ESCULAP in noncirrhotic liver in a prospective multicentre real-life setting. Methods High-risk patients for HCC with focal liver lesions upon B-mode ultrasound were recruited prospectively in a multicentre real-life approach to undergo standardized CEUS. Diagnostic accuracies of CEUS and the CEUS algorithms were assessed for the sub-collective of noncirrhotic patients. Histology, MRI and CT served as the reference standard. Results In total 47/517 patients were noncirrhotic. The reference standard of the lesions showed 30 HCCs (63.8%), four intrahepatic cholangiocellular carcinomas (iCCAs), two other malignancies and 11 benign lesions. HCCs in noncirrhosis showed a tendency towards larger tumor size and better differentiation. A typical CEUS pattern of arterial phase hyperenhancement and late-onset (>60 s), mild washout occurred in 22/30 HCCs (73.3%). Very late onset of washout > 4-6 min was not seen in noncirrhotic liver. The CEUS algorithm ESCULAP showed a perfect sensitivity (100 vs. 68% with CEUS LI-RADS), whereas CEUS LI-RADS had a superior specificity (83 vs. 53%). The positive predictive value was high with both algorithms. Conclusion The CEUS patterns of HCCs in noncirrhotic liver resembled those in cirrhosis. Our findings suggest that although designed for the application in cirrhosis only, the diagnostic accuracies of the CEUS algorithms in noncirrhotic liver seem comparable to the findings in cirrhosis.

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Assessment of arterial-phase hyperenhancement and late-phase washout of hepatocellular carcinoma—a meta-analysis of contrast-enhanced ultrasound (CEUS) with SonoVue® and Sonazoid®

Ren,

Lu,

Fei

et al. 2023

Eur Radiol

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Contrast-Enhanced Ultrasound Patterns for the Non-invasive Diagnosis of Hepatocellular Carcinoma: A Prospective Multicenter Study in Histologically Proven Liver Lesions in a Real-Life Setting Demonstrating the Benefit of Extended Late Phase Observation

Cited by 16 publications

References 19 publications

HCCs lacking arterial phase hyperenhancement (APHE) on contrast-enhanced ultrasound (CEUS) – a diagnostic challenge. Findings from the prospective multicenter DEGUM CEUS HCC trial

HCCs lacking arterial phase hyperenhancement (APHE) on contrast-enhanced ultrasound (CEUS) – a diagnostic challenge. Findings from the prospective multicenter DEGUM CEUS HCC trial

Contrast-enhanced ultrasound pattern of hepatocellular carcinoma in noncirrhotic liver – results from the prospective multicentre DEGUM CEUS HCC study

Assessment of arterial-phase hyperenhancement and late-phase washout of hepatocellular carcinoma—a meta-analysis of contrast-enhanced ultrasound (CEUS) with SonoVue® and Sonazoid®

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