Barbara Schellhaas

Diagnostic accuracy of contrast-enhanced ultrasound for the differential diagnosis of hepatocellular carcinoma: ESCULAP versus CEUS-LI-RADS

Objective A comparison is made of two contrast-enhanced ultrasound (CEUS) algorithms for the diagnosis of hepatocellular carcinoma (HCC) in high-risk patients: Erlanger Synopsis of Contrast-enhanced Ultrasound for Liver lesion Assessment in Patients at Risk (ESCULAP) and American College of Radiology Contrast-Enhanced Ultrasound-Liver Imaging Reporting and Data System (ACR-CEUS-LI-RADSv.2016). Patients and methods Focal liver lesions in 100 high-risk patients were assessed using both CEUS algorithms (ESCULAP and CEUS-LI-RADSv.2016) for a direct comparison. Lesions were categorized according to size and contrast enhancement in the arterial, portal venous and late phases. For the definite diagnosis of HCC, categories ESCULAP-4, ESCULAP-Tr and ESCULAP-V and CEUS-LI-RADS-LR-5, LR-Tr and LR-5-V were compared. In addition, CEUS-LI-RADS-category LR-M (definitely/probably malignant, but not specific for HCC) and ESCULAP-category C [intrahepatic cholangiocellular carcinoma (ICC)] were compared. Histology, CE-computed tomography and CE-MRI served as reference standards. Results The reference standard among 100 lesions included 87 HCCs, six ICCs and seven non-HCC-non-ICC-lesions. For the diagnosis of HCC, the diagnostic accuracy of CEUS was significantly higher with ESCULAP versus CEUS-LI-RADS (94.3%/72.4%; p<0.01). Sensitivity, specificity and positive predictive value (PPV) and negative predictive value for ESCULAP/CEUS-LI-RADS were 94.3%/72.4%; 61.5%/69.2%; 94.3%/94%; and 61.5%/27.3%, respectively. The diagnostic accuracy for ICC (LR-M/ESCULAP-C) was identical with both algorithms (50%), with higher PPV for ESCULAP-C versus LR-M (75 vs. 50%). Conclusion CEUS-based algorithms contribute toward standardized assessment and reporting of HCC-suspect lesions in high-risk patients. ESCULAP shows significantly higher diagnostic accuracy, sensitivity and negative predictive value with no loss of specificity compared with CEUS-LI-RADS. Both algorithms have an excellent PPV. Arterial hyperenhancement is the key feature for the diagnosis of HCC with CEUS. Washout should not be a necessary prerequisite for the diagnosis of definite HCC. CEUS-LI-RADS in its current version is inferior to ESCULAP for the noninvasive diagnosis of HCC. There are two ways to improve CEUS-LI-RADS: firstly, combination of the categories LR-4 and LR-5 for the diagnosis of definite HCC, and secondly, use of subtotal infiltration of a liver lobe as an additional feature.

Two-dimensional shear-wave elastography: a new method comparable to acoustic radiation force impulse imaging?

Objectives Two-dimensional shear-wave elastography (2D-SWE) is an ultrasound-based technique for the noninvasive assessment of tissue stiffness. In contrast to the well-established point-shear-wave elastography (pSWE) method acoustic radiation force impulse imaging, there is little evidence on the performance and usefulness of 2D-SWE in the assessment of liver stiffness. Thus, the aim of our study was to compare 2D-SWE versus pSWE. Materials and methods 2D-SWE and pSWE were performed in 20 cirrhotic patients, 20 healthy individuals and an elasticity phantom. Stiffness values, examination time and number of measurements were compared. For 2D-SWE, the influence of size of the region of interest (ROI) was assessed. Results Elastography values in healthy individuals were slightly higher for 2D-SWE versus pSWE (1.4 m/s, range: 1.21–1.68 vs. 1.23 m/s, range: 1.07–1.39). In cirrhotic patients, there were no significant differences (3.06 m/s, range: 1.83–5.35 vs. 3 m/s, range: 1.67–4.37 m/s). Examination times were significantly longer for 2D-SWE in both patient groups (mean values for healthy/cirrhotic patients: 129.6/157.1 vs. 75/71.6 s). For 2D-SWE, variation of ROI size (5, 10, 20 mm) produced comparable results. After eight measurements, 90% of cirrhotic patients showed less than 5% of deviation from the results after the gold standard of 10 measurements; for healthy individuals, this was observed after six measurements. Conclusion 2D-SWE seems to be comparable to pSWE (acoustic radiation force impulse-imaging) in cirrhotic patients, with slightly higher values in healthy individuals. 2D-SWE measurements require considerably more time. For 2D-SWE, ROI size seems to be of minor importance; multiple measurements should be obtained as single measurements differ. These preliminary results should be confirmed in larger patient collectives with histology as the reference standard.

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

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.

Interobserver and intermodality agreement of standardized algorithms for non-invasive diagnosis of hepatocellular carcinoma in high-risk patients: CEUS-LI-RADS versus MRI-LI-RADS

ObjectivesWe compared the interobserver agreement for the recently introduced contrast-enhanced ultrasound (CEUS)-based algorithm CEUS-LI-RADS (Liver Imaging Reporting and Data System) versus the well-established magnetic resonance imaging (MRI)-LI-RADS for non-invasive diagnosis of hepatocellular carcinoma (HCC) in high-risk patients.MethodsFocal liver lesions in 50 high-risk patients (mean age 66.2 ± 11.8 years; 39 male) were assessed retrospectively with CEUS and MRI. Two independent observers reviewed CEUS and MRI examinations, separately, classifying observations according to CEUS-LI-RADSv.2016 and MRI-LI-RADSv.2014. Interobserver agreement was assessed with Cohen’s kappa.ResultsForty-three lesions were HCCs; two were intrahepatic cholangiocarcinomas; five were benign lesions. Arterial phase hyperenhancement was perceived less frequently with CEUS than with MRI (37/50 / 38/50 lesions = 74%/78% [CEUS; observer 1/observer 2] versus 46/50 / 44/50 lesions = 92%/88% [MRI; observer 1/observer 2]). Washout appearance was observed in 34/50 / 20/50 lesions = 68%/40% with CEUS and 31/50 / 31/50 lesions = 62%/62%) with MRI. Interobserver agreement was moderate for arterial hyperenhancement (ĸ = 0.511/0.565 [CEUS/MRI]) and “washout” (ĸ = 0.490/0.582 [CEUS/MRI]), fair for CEUS-LI-RADS category (ĸ = 0.309) and substantial for MRI-LI-RADS category (ĸ = 0.609). Intermodality agreement was fair for arterial hyperenhancement (ĸ = 0.329), slight to fair for “washout” (ĸ = 0.202) and LI-RADS category (ĸ = 0.218)ConclusionInterobserver agreement is substantial for MRI-LI-RADS and only fair for CEUS-LI-RADS. This is mostly because interobserver agreement in the perception of washout appearance is better in MRI than in CEUS. Further refinement of the LI-RADS algorithms and increasing education and practice may be necessary to improve the concordance between CEUS and MRI for the final LI-RADS categorization.Key Points• CEUS-LI-RADS and MRI-LIRADS enable standardized non-invasive diagnosis of HCC in high-risk patients.• With CEUS, interobserver agreement is better for arterial hyperenhancement than for “washout”.• Interobserver agreement for major features is moderate for both CEUS and MRI.• Interobserver agreement for LI-RADS category is substantial for MRI, and fair for CEUS.• Interobserver-agreement for CEUS-LI-RADS will presumably improve with ongoing use of the algorithm.

Dynamics of Fukuoka Criteria and Patient Management in Pancreatic Intraductal Papillary Mucinous Neoplasms (IPMNs) During Follow-Up

Background Pancreatic intraductal papillary mucinous neoplasms (IPMNs) present a clinical challenge. Evidence-based guidelines are lacking. The so-called “Fukuoka criteria” were developed to assess the risk of malignancy in IPMNs upon imaging. However, little is known about their diagnostic value and the natural course of IPMNs. Thus, the aim of this study was the assessment of Fukuoka criteria and patient management in pancreatic IPMNs during follow-up. Material/Methods IPMNs were identified via retrospective survey of endoscopic ultrasound (EUS) examinations. Fukuoka criteria were assessed on EUS findings and additional imaging (CT, MRI, ultrasound). Patients’ symptoms and comorbidities were recorded. Dynamics of Fukuoka criteria and patient management were compared at first presentation and during follow-up. Results We screened 1324 EUS examinations. Sixty-five patients (male/female, 14/37; mean age, 68.8 years; range, 48–85 years) with IPMNs were identified (57 branch duct (BD-)IPMNs, 3 main duct (MD-) IPMNs, 5 mixed-type (MT)-IPMNs). Seven patients received surgical resection (4 BD-IPMNs, 2 MD-IPMNs, 1 MT-IPMN). Nine BD-IPMNs had neither surgery nor follow-up. Fifty-one patients (44 BD-IPMNs, 2 MD-IPMNs, 5 MT-IPMNs) underwent follow-up (mean duration, 18.7 months; range, 3–139 months). There were 15/51 patients who were initially Fukuoka-positive. One MD-IPMN, 4/5 MT-IPMNs, and 13/44 BD-IPMNs showed progressive changes but were not resected due to patients’ refusal or comorbidities. Four BD-IPMNs converted to Fukuoka-positive. Conclusions Evidence-based guidelines for non-invasive dignity assessment of IPMNs are lacking. In our study, MD-IPMNs displayed greater dynamics than BD-IPMNs and MT-IPMNs concerning Fukuoka criteria. Prospective long-term studies are needed to clarify prognostic significance of the single Fukuoka criteria and sensible duration of follow-up.

Acoustic radiation force impulse elastography: comparison and combination with other noninvasive tests for the diagnosis of compensated liver cirrhosis

Background and aims The aim of this study was to compare acoustic radiation force impulse (ARFI) elastography with other noninvasive tests and to develop a new score for the assessment of liver fibrosis/cirrhosis. Materials and methods B-mode ultrasound (including high-frequency liver surface evaluation), routine blood tests, ARFI quantification, and mini-laparoscopic liver evaluation were obtained in compensated patients scheduled for mini-laparoscopic biopsy. Our new cirrhosis score (CS) for the assessment of liver cirrhosis, based on a linear combination of ARFI, platelet (PLT), liver surface, and prothrombin index (PI), was calculated by linear discriminant analysis. Its performance was compared with ARFI-elastography, APRI, FIB-4, alanine aminotransferase (ALT)/aspartate aminotransferase (AST)-ratio, PLT, and PI. For the diagnosis of cirrhosis, a combined gold standard (cirrhosis at histology and/or at macroscopic liver evaluation) was used. Results In total, 171 patients, of whom 38 had compensated cirrhosis, were included. The CS was significantly better for the diagnosis of cirrhosis compared with ARFI (P=0.028), APRI (P=0.012), PLTs (P=0.013), PI (P=0.025), and ALT/AST ratio (P=0.001), but not the FIB-4 score (P=0.207), with an area under the receiver operating characteristic curve of 0.92 [95% confidence interval (CI): 0.87–0.97], 0.86 (95% CI:0.79–0.93), 0.80 (95% CI: 0.72–0.87), 0.79 (95% CI: 0.7–0.87), 0.81 (95% CI: 0.73–0.89), 0.72 (95% CI:0.64–0.81), and 0.86 (95% CI: 0.8–0.93), respectively. Sensitivity, specificity, positive predictive value, and negative predictive value for CS were 87%, 86%, 63%, and 96%, respectively. The FIB-4 score was significantly superior to the APRI score (P=0.041) and the ALT/AST ratio (P=0.011), with no significant difference from ARFI elastography (P=0.88) for the diagnosis of cirrhosis. Conclusion Combining ARFI elastography with other noninvasive tests that are used routinely in the workup of patients with suspected liver disease can improve diagnostic accuracy for compensated liver cirrhosis as compared with ARFI elastography alone. The FIB-4 score showed an overall comparable diagnostic accuracy to ARFI-elastography for compensated cirrhosis.