Ultraschall Med 2021; 42(02): 178-186
DOI: 10.1055/a-1198-4874
Original Article

Contrast-Enhanced Ultrasound Algorithms (CEUS-LIRADS/ESCULAP) for the Noninvasive Diagnosis of Hepatocellular Carcinoma – A Prospective Multicenter DEGUM Study

CEUS-Algorithmen für den kontrastverstärkten Ultraschall (CEUS-LIRADS/ESCULAP) in der nichtinvasiven Diagnostik des hepatozellulären Karzinoms – eine prospektive, multizentrische DEGUM-Studie
Barbara Schellhaas
1  Department of Internal Medicine 1, University Hospital Erlangen, Germany
,
Thomas Bernatik
2  Department of Internal Medicine 1, Kreisklinik Ebersberg gGmbH, Ebersberg, Germany
,
Wolfram Bohle
3  Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie und Infektiologie, Katharinenhospital, Klinikum Stuttgart, Germany
,
Fanny Borowitzka
4  Department of Internal Medicine 2, Universitätsmedizin Rostock, Germany
,
Johannes Chang
5  Department of Internal Medicine I, University Hospital Bonn, Germany
,
Christoph F. Dietrich
6  Medizinische Klinik 2, Caritas-Krankenhaus, Bad Mergentheim, Germany
,
Klaus Dirks
7  Gastroenterologie und Innere Medizin, Rems-Murr-Klinikum Winnenden, Germany
,
Robert Donoval
8  Klinik für Gastroenterologie, Diabetologie und Infektiologie, Lausitzer Seenland Klinikum GmbH, Hoyerswerda, Germany
,
Kristine Drube
9  Department of Internal Medicine, Allgemeines Krankenhaus Celle, Germany
,
Mireen Friedrich-Rust
10  Department of Internal Medicine 1, J.W. Goethe University Hospital, Frankfurt, Germany
,
Christine Gall
11  Institut für Medizininformatik, Biometrie und Epidemiologie, FAU IMBE, Erlangen, Germany
,
Fleur Gittinger
12  Department of Internal Medicine, University Hospital Halle, Halle, Germany
,
Martin Gutermann
13  Department of Internal Medicine, Hufeland-Hospital, Mühlhausen, Germany
,
Mark Martin Haenle
14  Department of Internal Medicine, University Hospital Ulm, Germany
,
Alexandra von Herbay
15  Department of Internal Medicine, Evangelisches Krankenhaus Hamm gGmbH, Hamm, Germany
,
Chau Hong Ho
13  Department of Internal Medicine, Hufeland-Hospital, Mühlhausen, Germany
,
Rico Hochdoerffer
16  Department of Internal Medicine, Städtisches Klinikum Karlsruhe gGmbH, Karlsruhe, Germany
,
Tatjana Hoffmann
17  Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany
,
Matthias Hüttig
18  Department of Internal Medicine, DRK-Kliniken Berlin-Köpenick, Berlin, Germany
,
Christopher Janson
19  Department of Internal Medicine, Städtisches Klinikum Braunschweig gGmbH, Braunschweig, Germany
,
Ernst-Michael Jung
20  Department of Radiology, Universitätsklinikum Regensburg, Germany
,
Norbert Jung
21  Department of Internal Medicine, Klinikum Heidenheim, Germany
,
Thomas Karlas
22  Department of Internal Medicine, Division of Gastroenterology, Universitätsklinikum Leipzig, Germany
,
Christoph Klinger
23  Medizinische Klinik I, Klinikum Ludwigsburg, Ludwigsburg, Germany
,
Adam Kornmehl
24  Department of Internal Medicine, Klinikum Weiden, Germany
,
Wolfgang Kratzer
14  Department of Internal Medicine, University Hospital Ulm, Germany
,
Sebastian Krug
12  Department of Internal Medicine, University Hospital Halle, Halle, Germany
,
Georg Kunze
25  Internal Medicine, KH Villingen-Schwenningen, Villingen-Schwenningen, Germany
,
Jens Leitlein
26  Department of Internal Medicine, Klinikum am Steinenberg Reutlingen, Germany
,
Alexander Link
27  Department of Internal Medicine, University Hospital Magdeburg, Germany
,
Christian Lottspeich
28  Medical Clinic and Policlinic IV, Division of Vascular Medicine, Hospital of the Ludwig Maximilians University Hospital, Munich, Germany
,
Aldo Marano
29  Department of Internal Medicine, ViDia Christliche Kliniken Karlsruhe, Germany
,
Martin Mauch
30  Department of Internal Medicine, Innere, Kreisklinik Sigmaringen, Germany
,
Lukas Moleda
31  Department of Internal Medicine, Universitätsklinikum Regensburg, Germany
,
Albrecht Neesse
32  Klinik für Gastroenterologie, gastrointestinale Onkologie und Endokrinologie, Universitätsmedizin Göttingen, Göttingen, Germany
,
Golo Petzold
32  Klinik für Gastroenterologie, gastrointestinale Onkologie und Endokrinologie, Universitätsmedizin Göttingen, Göttingen, Germany
,
Andrej Potthoff
33  Gastroenterology and Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
,
Michael Praktiknjo
5  Department of Internal Medicine I, University Hospital Bonn, Germany
,
Klaus-Dieter Rösner
34  Department of Internal Medicine, Barmherzige Brüder Klinikum Sankt Elisabeth Straubing GmbH, Straubing, Germany
,
Stefan Schanz
35  Department of Internal Medicine, Kreisklinikum Siegen gGmbH, Siegen, Germany
,
Michael Schultheiß
36  Department of Internal Medicine, University of Freiburg Hospital, Freiburg, Germany
,
Visvakanth Sivanathan
37  Department of Internal Medicine, University Hospital Mainz, Department of Internal Medicine 3, Mainz, Germany
,
Joachim Stock
38  Department of Internal Medicine, Klinikum Barnim, Eberswalde, Germany
,
Thomas Thomsen
39  Department of Internal Medicine, Westküstenklinik Brunsbüttel, Brunsbüttel, Germany
,
Johanna Vogelpohl
40  Department of Internal Medicine I, Krankenhaus GmbH Alb-Donau-Kreis Blaubeuren, Germany
,
Christoph Vogt
41  Department of Internal Medicine, St.-Josef-Krankenhaus Moers, Germany
,
Siegfried Wagner
42  Department of Internal Medicine, Donau-Isar-Kliniken Deggendorf, Germany
,
Christiane Wiegard
43  Department of Internal Medicine, University Hospital Hamburg Eppendorf Center of Internal Medicine, Hamburg, Germany
,
Isabel Wiesinger
31  Department of Internal Medicine, Universitätsklinikum Regensburg, Germany
,
Uwe Will
44  Internal Medicine, Klinikum Gera, Gera, Germany
,
Matthias Ziesch
45  Department of Internal Medicine, Diakonissenkrankenhaus Dresden, Germany
,
Patrick Zimmermann
44  Internal Medicine, Klinikum Gera, Gera, Germany
,
Deike Strobel
1  Department of Internal Medicine 1, University Hospital Erlangen, Germany
› Author Affiliations
Supported by: DEGUM (Deutsche Gesellschaft für Ultraschall in der Medizin)

Abstract

Background This prospective multicenter study funded by the DEGUM assesses the diagnostic accuracy of standardized contrast-enhanced ultrasound (CEUS) for the noninvasive diagnosis of hepatocellular carcinoma (HCC) in high-risk patients.

Methods Patients at high risk for HCC with a histologically proven focal liver lesion on B-mode ultrasound were recruited prospectively in a multicenter approach. Clinical and imaging data were entered via online entry forms. The diagnostic accuracies for the noninvasive diagnosis of HCC were compared for the conventional interpretation of standardized CEUS at the time of the examination (= CEUS on-site) and the two CEUS algorithms ESCULAP (Erlanger Synopsis for Contrast-enhanced Ultrasound for Liver lesion Assessment in Patients at risk) and CEUS LI-RADS (Contrast-Enhanced UltraSound Liver Imaging Reporting and Data System).

Results 321 patients were recruited in 43 centers; 299 (93.1 %) had liver cirrhosis. The diagnosis according to histology was HCC in 256 cases, and intrahepatic cholangiocarcinoma (iCCA) in 23 cases. In the subgroup of cirrhotic patients (n = 299), the highest sensitivity for the diagnosis of HCC was achieved with the CEUS algorithm ESCULAP (94.2 %) and CEUS on-site (90.9 %). The lowest sensitivity was reached with the CEUS LI-RADS algorithm (64 %; p < 0.001). However, the specificity of CEUS LI-RADS (78.9 %) was superior to that of ESCULAP (50.9 %) and CEUS on-site (64.9 %; p < 0.001). At the same time, the negative predictive value (NPV) of CEUS LI-RADS was significantly inferior to that of ESCULAP (34.1 % vs. 67.4 %; p < 0.001) and CEUS on-site (62.7 %; p < 0.001). The positive predictive values of all modalities were high (around 90 %), with the best results seen for CEUS LI-RADS and CEUS on-site.

Conclusion This is the first multicenter, prospective comparison of standardized CEUS and the recently developed CEUS-based algorithms in histologically proven liver lesions in cirrhotic patients. Our results reaffirm the excellent diagnostic accuracy of CEUS for the noninvasive diagnosis of HCC in high-risk patients. However, on-site diagnosis by an experienced examiner achieves an almost equal diagnostic accuracy compared to CEUS-based diagnostic algorithms.

Zusammenfassung

Hintergrund Diese prospektive, multizentrische, DEGUM-geförderte Studie untersucht die diagnostische Genauigkeit standardisierter Algorithmen für die Kontrastmittelsonografie (CEUS-Algorithmen) in der nichtinvasiven Diagnostik des hepatozellulären Karzinoms (HCC) bei Hochrisikopatienten.

Methoden HCC-Hochrisikopatienten mit histologisch gesicherter Leberläsion im B-Bild-Ultraschall wurden prospektiv multizentrisch eingeschlossen. Klinische Daten und Bildgebungsbefunde wurden über Online-Eingabemasken erfasst. Es erfolgte ein direkter Vergleich der diagnostischen Genauigkeiten für die konventionelle CEUS-Befundung zum Untersuchungszeitpunkt (CEUS-on-site) und die CEUS-Algorithmen ESCULAP (Erlanger Synopsis for Contrast-enhanced Ultrasound for Liver lesion Assessment in Patients at risk) und CEUS LI-RADS (Contrast-Enhanced UltraSound Liver Imaging Reporting and Data System).

Ergebnisse 321 Patienten an 43 Zentren wurden eingeschlossen (93,1 % Leberzirrhose). Der histologische Befund ergab 256 HCCs und 23 intrahepatische cholangiozelluläre Karzinome (iCCA). Die höchste Sensitivität bei Zirrhose-Patienten (n = 299) erzielten der CEUS-Algorithmus ESCULAP (94,2 %) und CEUS-on-site (90,9 %), die geringste Sensitivität der CEUS LI-RADS-Algorithmus (64 %; p < 0,001). Die Spezifität war höher für CEUS LI-RADS (78,9 %) versus ESCULAP (50,9 %) und CEUS on-site (64,9 %; p < 0,001). Der negativ prädiktive Wert (NPW) war für CEUS LI-RADS niedriger als für ESCULAP (34,1 % vs. 67,4 %; p < 0,001) und CEUS-on-site (62,7 %; p < 0,001). Der positiv prädiktive Wert (PPW) war für alle Modalitäten hoch (rund 90 %).

Schlussfolgerungen Dies ist die erste prospektive, multizentrische Studie zum Vergleich der standardisierten Kontrastmittelsonografie mit den kürzlich entwickelten CEUS-Algorithmen in histologisch gesicherten Leberläsionen bei Zirrhose-Patienten. Unsere Ergebnisse bestätigen die exzellente diagnostische Genauigkeit der Kontrastmittelsonografie in der nichtinvasiven HCC-Diagnostik bei Hochrisikopatienten. Die On-site-Diagnose eines erfahrenen Untersuchers erzielt dabei eine beinahe ebenso gute diagnostische Genauigkeit wie die CEUS-basierten Diagnosealgorithmen



Publication History

Received: 12 December 2019

Accepted: 04 June 2020

Publication Date:
14 July 2020 (online)

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