Limited added value of contrast-enhanced ultrasound over B-mode for the subtyping of hepatocellular adenomas.

PURPOSE: To compare the features of hepatocellular adenoma subtypes (HCAs) in B-mode and contrast-enhanced ultrasound (CEUS). METHOD: Thirty-three patients (31 women [94 %] and two men [6%], median age [Q1-Q3] 43.5 years old [35-51]) with 44 pathologically proven and subtyped HCAs (including 29 inflammatory HCAs [I-HCA] and 15 HNF1-α inactivated HCAs [H-HCA]) who underwent CEUS were included. The features of HCA on B-mode and CEUS were independently reviewed by two radiologists and compared between HCA subtypes. RESULTS: I-HCAs were mostly hypoechoic (23/29, 79 %) or isoechoic (4/29, 14 %) with B-mode. Twelve of them (41 %) were heterogeneous. All H-HCAs except one demonstrated homogeneous hyperechogenicity (93 %) (p = 0.001). Moderate or marked liver steatosis was only observed in I-HCAs (12/29, 41 %) (p = 0.001). Arterial hyperenhancement was observed on CEUS in 27/29 (93 %) I-HCAs and in 14/15 (93 %) H-HCAs (p=0.98). Washout was present in 6/29 (21 %) I-HCAs and 1/15 (7%) H-HCAs (p=0.27). A total of 23/29 (79 %) I-HCAs and 15/15 (100 %) HCAs were homogeneous on portal and delayed phase acquisitions (p=0.04). The specificity for identifying an H-HCA was 100 % when the lesion was homogeneous and hyperechoic on B-mode, and the sensibility to rule out an H-HCA was 100 % if neither of these two features was present in a liver with obvious steatosis. CONCLUSIONS: Most CEUS features, especially enhancement patterns, do not significantly differ between HCA subtypes. When HCA is suspected on CEUS, B-mode features should be considered, and a combination of lesion hyperechogenicity, homogeneity and the absence of obvious liver steatosis may be useful to distinguish H-HCAs from I-HCAs.

Combining imaging and tumour biopsy improves the diagnosis of combined hepatocellular-cholangiocarcinoma.

BACKGROUND & AIMS: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is by definition a highly heterogeneous tumour, which significantly impacts its diagnosis. The aim of the study was to evaluate the diagnostic performance of imaging using computed tomography and/or magnetic resonance (MR) and biopsy for the diagnosis of cHCC-CCA. METHODS: cHCC-CCA resected between December 2006 and April 2017 with available pre-operative imaging and tumour biopsy were retrospectively included. cHCC-CCA diagnosis was based on morphological and immunophenotypical features. A total of 21 cHCC-CCA were compared to 21 intrahepatic cholangiocarcinoma (iCCA) as controls. All biopsies were reviewed. Two radiologists reviewed the cases and classified tumours into four patterns (type 1 [progressive enhancement of the entire lesion, iCCA type], type 2 [arterial enhancement with washout, HCC type], type 3 [mixed pattern with combinations of 1, 2 and 4] and type 4 [atypical pattern, areas of arterial enhancement without washout and/or hypovascular]). RESULTS: The presence of a type 3 pattern at imaging had a 48% sensitivity and 81% specificity for cHCC-CCA diagnosis. The initial diagnosis performed on biopsy was cHCC-CCA in 8/21 patients (38%). After reviewing and including immunophenotypical markers, two more cases were diagnosed as cHCC-CCA (48% sensibility, 100% specificity). When either imaging or biopsy suggested the diagnosis of cHCC-CCA, the sensitivity and specificity were 60% and 82% respectively. CONCLUSIONS: We showed that a two-step strategy combining imaging as the first step and biopsy as the second step improved the diagnostic performance of cHCC-CCA.

Contrast-enhanced ultrasound of focal nodular hyperplasia: a matter of size.

OBJECTIVES: To assess the contrast-enhanced ultrasound (CEUS) frequencies of centrifugal enhancement, spoke-wheel sign and central scar in focal nodular hyperplasia (FNH) as a function of lesion size. METHODS: Ninety-four FNHs were retrospectively reviewed to assess their largest diameter and enhancement pattern, including centrifugal enhancement from one central artery, spoke-wheel sign, diffuse or centripetal enhancement, central scar and late-phase washout. RESULTS: Mean FNH-lesion size was 3.7 ± 2.1 cm. Only 43.6 % of FNHs had centrifugal enhancement, with a spoke-wheel pattern (23.4 %) or without (20.2 %), while 56.4 % showed diffuse or centripetal enhancement. Centrifugal enhancement was observed in 73.9 % of FNHs ≤3.1 cm and 14.6 % of FNHs >3.1 cm (P < 10(-4)). Size and frequency of centrifugal enhancement were negatively correlated (r = -0.57, P < 10(-4)). The spoke-wheel pattern was also seen more frequently in smaller (37 %) than in larger FNHs (10.4 %) (P < 10(-3)). Late-phase washout was described in 5.3 % of FNHs and was not size-dependent. Lesions with a central scar were larger than those without, respectively, 5.7 ± 1.7 and 3.6 ± 2.0 cm (P = 0.012). CONCLUSIONS: Typical centrifugal enhancement yielding a confident FNH diagnosis is seen significantly more frequently when the lesion is ≤3.1 cm. KEY POINTS: • CEUS yields confident diagnoses of FNHs ≤3.1 cm • The larger the FNH, the lower the diagnostic sensitivity of CEUS • Final diagnosis of FNHs >3.1 cm should be obtained with MRI not CEUS.

Contrast-enhanced ultrasound (CEUS) follow-up after radiofrequency ablation or cryoablation of focal liver lesions: treated-area patterns and their changes over time.

OBJECTIVES: To describe the early patterns of liver lesions successfully treated with radiofrequency ablation (RFA) or cryoablation (CA) and their changes over time. METHODS: Twenty-two RFA-treated and 17 CA-treated patients underwent CEUS from week 1 to year 3 post-ablation. Patterns, margins and volumes of RF-induced and cryolesions were evaluated and compared over time. RESULTS: After contrast enhancement, shortly after ablation, undefined margins with persistent enhancing small vessels penetrating >2 mm into the treated zone were significantly more frequent after CA (67 %) than RFA (22 %) (P < 0.02). During the arterial phase, a thin, enhancing marginal rim was seen during week 1 (T1) in around 28 % of RF lesions, while 75 % of cryolesions had thick enhancing rims (P < 0.02). The mean RF-induced lesion volume, maximum at T1 (44.1 ± 37.5 ml), shrank slowly over time, remaining clearly visible at 1 year (8.3 ± 7.4 ml). Cryolesions shrank faster (P = 0.009), from an average of 16.6 ± 7.1 ml at T1 to 1.7 ± 1.3 ml 1-year post-ablation. CONCLUSION: RF-induced and cryolesions differ, particularly their margins and shrinkage rates. Knowing these differences allows avoidance of incomplete treatment or falsely diagnosed recurrence, especially after CA. KEY POINTS: • Contrast-enhanced ultrasound (CEUS) provides new follow-up information following hepatic radiological inyervention. • CEUS provides good visualisation of vascular modifications after thermoablation. • RFA-induced lesions and cryoablated lesions differ. • Knowledge about RF and cryolesion patterns is essential for correct CEUS follow-up. • Cryolesions have thicker peripheral inflammatory reactions and shrink faster than RFA-induced lesions.

Pancreas divisum is not a cause of pancreatitis by itself but acts as a partner of genetic mutations.

OBJECTIVES: The role of pancreas divisum (PD) as a cause of acute recurrent or chronic pancreatitis (AR/CP) is still a matter of debate. METHODS: The aims of this study were to evaluate the frequency of PD diagnosed using magnetic resonance cholangiopancreatography (MRCP) in patients with AR/CP of unknown origin (n=40) after careful exclusion of all known causes and to test the hypothesis of an interaction between anatomical (PD) and functional genetic anomalies (SPINK1, PRSS1, or CFTR gene mutations or polymorphisms (n=19, 25, and 30, respectively)) that could result in AR/CP. Patients with alcohol-induced pancreatitis (n=29) and subjects who had MRCP for a nonpancreatic disease (n=45) served as controls. RESULTS: PD frequency was 7% in subjects without pancreatic disease, 7% in patients with alcohol-induced pancreatitis, and 5, 16, 16, and 47% in those with idiopathic, and PRSS1-, SPINK1-, and CFTR-associated pancreatitis, respectively (P<0.0001). There was no significant difference between idiopathic pancreatitis and the two control groups. The frequency of PD was higher in patients with CFTR gene-associated pancreatitis as compared with those with idiopathic and alcoholic pancreatitis (P<0.0001) and with those with SPINK1 and PRSS1 gene-associated pancreatitis (P<0.02). CONCLUSIONS: The frequency of PD was not different in patients with idiopathic pancreatitis as compared with controls, demonstrating that PD by itself is not a cause of pancreatitis. PD frequency was higher in patients with genetic pancreatitis, especially in those with CFTR mutations or polymorphisms, suggesting a cumulative effect of these two cofactors.

Assessing the validity domains of graphical Gaussian models in order to infer relationships among components of complex biological systems.

The study of the interactions of cellular components is an essential base step to understand the structure and dynamics of biological networks. Various methods were recently developed for this purpose. While most of them combine different types of data and a priori knowledge, methods based on graphical Gaussian models are capable of learning the network directly from raw data. They consider the full-order partial correlations which are partial correlations between two variables given the remaining ones, for modeling direct links between variables. Statistical methods were developed for estimating these links when the number of observations is larger than the number of variables. However, the rapid advance of new technologies that allow the simultaneous measure of genome expression, led to large-scale datasets where the number of variables is far larger than the number of observations. To get around this dimensionality problem, different strategies and new statistical methods were proposed. In this study we focused on statistical methods recently published. All are based on the fact that the number of direct relationships between two variables is very small in regards to the number of possible relationships, p(p-1)/2. In the biological context, this assumption is not always satisfied over the whole graph. It is essential to precisely know the behavior of the methods in regards to the characteristics of the studied object before applying them. For this purpose, we evaluated the validity domain of each method from wide-ranging simulated datasets. We then illustrated our results using recently published biological data.