Ultrasound-based steatosis grading system using 2D-attenuation imaging: An individual patient data meta-analysis with external validation.

BACKGROUND AND AIMS: Noninvasive tools assessing steatosis, such as ultrasonography-based 2D-attenuation imaging (ATI), are needed to tackle the worldwide burden of steatotic liver disease. This one-stage individual patient data (IPD) meta-analysis aimed to create an ATI-based steatosis grading system. APPROACH AND RESULTS: A systematic review (EMBASE + MEDLINE, 2018-2022) identified studies, including patients with histologically or magnetic resonance imaging proton-density fat fraction (MRI-PDFF)-verified ATI for grading steatosis (S0 to S3). One-stage IPD meta-analyses were conducted using generalized mixed models with a random study-specific intercept. Created ATI-based steatosis grading system (aS0 to aS3) was externally validated on a prospective cohort of patients with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (n=174, histologically and MRI-PDFF-verified steatosis). Eleven enrolled studies included 1374 patients, classified into S0, S1, S2, and S3 in 45.4%, 35.0%, 9.3%, and 10.3% of the cases. ATI was correlated with histological steatosis ( r = 0.60; 95% CI: 0.52, 0.67; p < 0.001) and MRI-PDFF ( r = 0.70; 95% CI: 0.66, 0.73; p < 0.001) but not with liver stiffness ( r = 0.03; 95% CI: -0.04, 0.11, p = 0.343). Steatosis grade was an independent factor associated with ATI (coefficient: 0.24; 95% CI: [0.22, 0.26]; p < 0.001). ATI marginal means within S0, S1, S2, and S3 subpopulations were 0.59 (95% CI: [0.58, 0.61]), 0.69 (95% CI [0.67, 0.71]), 0.78 (95% CI: [0.76, 0.81]), and 0.85 (95% CI: [0.83, 0.88]) dB/cm/MHz; all contrasts between grades were significant ( p < 0.0001). Three ATI thresholds were calibrated to create a new ATI-based steatosis grading system (aS0 to aS3, cutoffs: 0.66, 0.73, and 0.81 dB/cm/MHz). Its external validation showed Obuchowski measures of 0.84 ± 0.02 and 0.82 ± 0.02 with histologically based and MRI-PDFF-based references. CONCLUSIONS: ATI is a reliable, noninvasive marker of steatosis. This validated ATI-based steatosis grading system could be valuable in assessing patients with metabolic dysfunction-associated steatotic liver disease.

Association of LI-RADS and Histopathologic Features with Survival in Patients with Solitary Resected Hepatocellular Carcinoma.

Background Both Liver Imaging Reporting and Data System (LI-RADS) and histopathologic features provide prognostic information in patients with hepatocellular carcinoma (HCC), but whether LI-RADS is independently associated with survival is uncertain. Purpose To assess the association of LI-RADS categories and features with survival outcomes in patients with solitary resected HCC. Materials and Methods This retrospective study included patients with solitary resected HCC from three institutions examined with preoperative contrast-enhanced CT and/or MRI between January 2008 and December 2019. Three independent readers evaluated the LI-RADS version 2018 categories and features. Histopathologic features including World Health Organization tumor grade, microvascular and macrovascular invasion, satellite nodules, and tumor capsule were recorded. Overall survival and disease-free survival were assessed with Cox regression models. Marginal effects of nontargetoid features on survival were estimated using propensity score matching. Results A total of 360 patients (median age, 64 years [IQR, 56-70 years]; 280 male patients) were included. At CT and MRI, the LI-RADS LR-M category was associated with increased risk of recurrence (CT: hazard ratio [HR] = 1.83 [95% CI: 1.26, 2.66], P = .001; MRI: HR = 2.22 [95% CI: 1.56, 3.16], P < .001) and death (CT: HR = 2.47 [95% CI: 1.72, 3.55], P < .001; MRI: HR = 1.80 [95% CI: 1.32, 2.46], P < .001) independently of histopathologic features. The presence of at least one nontargetoid feature was associated with an increased risk of recurrence (CT: HR = 1.80 [95% CI: 1.36, 2.38], P < .001; MRI: HR = 1.93 [95% CI: 1.81, 2.06], P < .001) and death (CT: HR = 1.51 [95% CI: 1.10, 2.07], P < .010) independently of histopathologic features. In matched samples, recurrence was associated with the presence of at least one nontargetoid feature at CT (HR = 2.06 [95% CI: 1.15, 3.66]; P = .02) or MRI (HR = 1.79 [95% CI: 1.01, 3.20]; P = .048). Conclusion In patients with solitary resected HCC, LR-M category and nontargetoid features were negatively associated with survival independently of histopathologic characteristics. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Kartalis and Grigoriadis in this issue.

Adherence to LI-RADS and EASL high-risk population criteria: A systematic review.

BACKGROUND AND AIMS: The Liver Imaging Reporting and Data System (LI-RADS) and European Association for the Study of the Liver (EASL) diagnostic criteria for noninvasive diagnosis of HCC can only be applied to patients at a high risk of HCC. This systematic review assesses adherence to the LI-RADS and EASL high-risk population criteria in published studies. APPROACH AND RESULTS: PubMed was searched for original research, published between January 2012 and December 2021, reporting LI-RADS and EASL diagnostic criteria on contrast-enhanced ultrasound, CT, or MRI. The algorithm version, publication year, risk status, and etiologies of chronic liver disease were recorded for each study. Adherence to high-risk population criteria was evaluated as optimal (unequivocal adherence), suboptimal (equivocal), or inadequate (clear violation). A total of 219 original studies were included, with 215 that used the LI-RADS criteria, 4 EASL only, and 15 that evaluated both LI-RADS and EASL criteria. Optimal, suboptimal, or inadequate adherence to high-risk population criteria was observed in 111/215 (51.6%), 86/215 (40.0%), and 18/215 (8.4%) LI-RADS and 6/19 (31.6%), 5/19 (26.3%), and 8/19 (42.1%) EASL studies ( p < 0.001) regardless of the imaging modality. Adherence to high-risk population criteria significantly improved according to the CT/MRI LI-RADS versions (optimal in v2018 in 64.5% of studies; v2017, 45.8%; v2014, 24.4%; v2013.1, 33.3%; p < 0.001) and the publication year (2020-2021, 62.5%; 2018-2019, 33.9%; 2014-2017, 39.3% of all LI-RADS studies; p = 0.002). No significant differences in adherence to high-risk population criteria were observed in the versions of contrast-enhanced ultrasound LI-RADS ( p = 0.388) or EASL ( p = 0.293). CONCLUSION: Adherence to high-risk population criteria was optimal or suboptimal in about 90% and 60% of LI-RADS and EASL studies, respectively.

Hepatocellular carcinoma in patients with non-alcoholic fatty liver disease is associated with heterogeneous pattern of fat infiltration in skeletal muscles.

OBJECTIVES: To evaluate the association between fat infiltration in skeletal muscles (myosteatosis) and hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: In a cross-sectional cohort of 72 histologically proven NAFLD patients (n = 38 with non-alcoholic steatohepatitis; NASH), among which 20 had HCC diagnosed on biopsy, we used proton density fat fraction (PDFF) at MRI to evaluate myosteatosis in skeletal muscles (mean fat fraction and first order radiomic-based pattern) at the third lumbar level, namely in erector spinae (ES), quadratus lumborum (QL), psoas, oblique, and rectus muscles. RESULTS: PDFFES was 70% higher in patients with HCC when compared to those without HCC (9.6 ± 5.5% versus 5.7 ± 3.0%, respectively, p < 0.001). In multivariate logistic regression, PDFFES was a significant predictor of the presence of HCC (AUC = 0.72, 95% CI 0.57-0.86, p = 0.002) independently from age, sex, visceral fat area, and liver fibrosis stage (all p < 0.05). The relationship between PDFFES and HCC was exacerbated in patients with NASH (AUC = 0.79, 95% CI 0.63-0.86, p = 0.006). In patients with NASH, radiomics features of heterogeneity such as energy and entropy in any of the paraspinal muscles (i.e., ES, QL, or psoas) were independent predictors of HCC. EnergyES identified patients with HCC (n = 13) in the NASH population with AUC = 0.92 (95% CI 0.82-1.00, p < 0.001). CONCLUSION: In patients with NAFLD, and more specifically in those with NASH, the degree and heterogeneity of myosteatosis is independently associated with HCC irrespective of liver fibrosis stage. CLINICAL RELEVANCE STATEMENT: Our data suggest that myosteatosis could be used as a biomarker of HCC in the ever-expanding NAFLD population and pave the way for further investigation in longitudinal studies. KEY POINTS: • HCC in patients with non-alcoholic fatty liver disease, and more specifically in those with non-alcoholic steatohepatitis, is independently associated with severe fatty infiltration (myosteatosis) of paravertebral skeletal muscles. • Association between myosteatosis and HCC is independent from liver fibrosis stage. • Histogram-based radiomics features of myosteatosis predicts the risk of HCC in patients with non-alcoholic steatohepatitis.

Imaging and prognostic characterization of fat-containing hepatocellular carcinoma subtypes.

PURPOSE: Steatohepatitic hepatocellular carcinoma (SH-HCC) is characterized by intratumoral fat with > 50% inflammatory changes. However, intratumoral fat (with or without inflammation) can also be found in not-otherwise specified HCC (NOS-HCC). We compared the imaging features and outcome of resected HCC containing fat on pathology including SH-HCC (> 50% steatohepatitic component), NOS-HCC with < 50% steatohepatitic component (SH-NOS-HCC), and fatty NOS-HCC (no steatohepatitic component). MATERIAL AND METHODS: From September 2012 to June 2021, 94 patients underwent hepatic resection for fat-containing HCC on pathology. Imaging features and categories were assessed using LIRADS v2018. Fat quantification was performed on chemical-shift MRI. Recurrence-free and overall survival were estimated. RESULTS: Twenty-one patients (26%) had nonalcoholic steatohepatitis (NASH). The median intra-tumoral fat fraction was 8%, with differences between SH-HCC and SH-NOS-HCC (9.5% vs. 5% p = 0.03). There was no difference in major LI-RADS features between all groups; most tumors were classified as LR-4/5. A mosaic architecture on MRI was rare (7%) in SH-HCC, a fat in mass on CT was more frequently depicted (48%) in SH-HCC. A combination of NASH with no mosaic architecture on MRI or NASH with fat in mass on CT yielded excellent specificity for diagnosing SH-HCC (97.6% and 97.7%, respectively). The median recurrence-free and overall survival were 58 and 87 months, with no difference between groups (p = 0.18 and p = 0.69). CONCLUSION: In patients with NASH, an SH-HCC may be suspected in L4/LR-5 observations with no mosaic architecture at MRI or with fat in mass on CT. Oncological outcomes appear similar between fat-containing HCC subtypes.

Prospective Comparison of Attenuation Imaging and Controlled Attenuation Parameter for Liver Steatosis Diagnosis in Patients With Nonalcoholic Fatty Liver Disease and Type 2 Diabetes.

BACKGROUND & AIMS: Similarly to the controlled attenuation parameter (CAP), the ultrasound-based attenuation imaging (ATI) can quantify hepatic steatosis. We prospectively compared the performance of ATI and CAP for the diagnosis of hepatic steatosis in patients with type 2 diabetes and nonalcoholic fatty liver disease using histology and magnetic resonance imaging-proton density fat fraction (MRI-PDFF) as references. METHODS: Patients underwent ATI and CAP measurement, MRI, and biopsy on the same day. Steatosis was classified as S0, S1, S2, and S3 on histology (<5%, 5%-33%, 33%-66%, and >66%, respectively) while the thresholds of 6.4%, 17.4%, and 22.1%, respectively, were used for MRI-PDFF. The area under the curve (AUC) of ATI and CAP was compared using a DeLong test. RESULTS: Steatosis could be evaluated in 191 and 187 patients with MRI-PDFF and liver biopsy, respectively. For MRI-PDFF steatosis, the AUC of ATI and CAP were 0.86 (95% confidence interval [CI], 0.81-0.91) vs 0.69 (95% CI, 0.62-0.75) for S0 vs S1-S3 (P = .02) and 0.71 (95% CI, 0.64-0.77) vs 0.69 (95% CI, 0.61-0.75) for S0-S1 vs S2-S3 (P = .60), respectively. For histological steatosis, the AUC of ATI and CAP were 0.92 (95% CI, 0.87-0.95) vs 0.95 (95% CI, 0.91-0.98) for S0 vs S1-S3 (P = .64) and 0.79 (95% CI, 0.72-0.84) vs 0.76 (95% CI, 0.69-0.82) for S0-S1 vs S2-S3 (P = .61), respectively. CONCLUSION: ATI may be used as an alternative to CAP for the diagnosis and quantification of steatosis, in patients with type 2 diabetes and nonalcoholic fatty liver disease.

Contrast-enhanced CT and liver surface nodularity for the diagnosis of porto-sinusoidal vascular disorder: A case-control study.

BACKGROUND AND AIMS: Porto-sinusoidal vascular disorder (PSVD) is a rare and commonly overlooked cause of portal hypertension. The interest of CT analysis, including quantification of liver surface nodularity (LSN) for PSVD diagnosis has not been established. This study aimed at assessing the performance of LSN and CT features for a PSVD diagnosis in patients with signs of portal hypertension. APPROACH AND RESULTS: This retrospective case-control study included a learning cohort consisting of 50 patients with histologically proven PSVD, according to VALDIG criteria, and 100 control patients with histologically proven cirrhosis, matched on ascites. All patients and controls had at least one sign of portal hypertension and CT available within 1 year of liver biopsy. Principal component analysis of CT features separated patients with PSVD from patients with cirrhosis. Patients with PSVD had lower median LSN than those with cirrhosis (2.4 vs. 3.1, p < 0.001). Multivariate analysis identified LSN < 2.5 and normal-sized or enlarged segment IV as independently associated with PSVD. Combination of these two features had a specificity of 90% for PSVD and a diagnostic accuracy of 84%. Even better results were obtained in an independent multicenter validation cohort including 53 patients with PSVD and 106 control patients with cirrhosis (specificity 94%, diagnostic accuracy 87%). CONCLUSIONS: This study that included a total of 103 patients with PSVD and 206 patients with cirrhosis demonstrates that LSN < 2.5 combined with normal-sized or enlarged segment IV strongly suggests PSVD in patients with signs of portal hypertension.

Who publishes imaging articles in non-imaging journals? A large sample data-mining study.

OBJECTIVES: To assess the weight of imaging and imaging specialists (i.e., affiliated to a radiology/nuclear medicine department) in publications in non-imaging journals. METHODS: All articles indexed in English on the Embase database between 1989 and 2019 were extracted. The number and affiliation of authors were determined. A naive Bayesian classifier algorithm was trained to classify abstracts as "imaging" or "non-imaging." The main outcome was the number and position of imaging specialists in the authorship of imaging articles published in non-imaging journals. Analyses per medical specialties and per journal impact factor (IF) were performed. RESULTS: A total of 15,787,825 articles were included with 968,259 (6%) "imaging" articles. The proportion of imaging articles increased over time (+ 370%), quicker than the overall academic output. The proportion of imaging specialist among authors grew from 0.58% in 1989-1994 to 1.54% in 2015-2019. About 20% of imaging articles had ≥ 1 imaging specialist among authors. The proportion of imaging articles decreased with the IF (7.3% for IF 0-2.5 vs. 5.1% for IF > 10, p < 0.001), but the proportion of imaging specialist authors in imaging papers with ≥ 1 imaging specialist author increased with the IF (40% for IF 0-2.5, 53% for IF > 10, p < 0.001). There was significant variability across medical specialties. CONCLUSIONS: The weight of imaging articles and imaging specialist among authors in non-imaging journals has increased over time but remains limited. Most of the authors of imaging publications are not imaging specialists. Imaging specialists among authors in imaging papers are associated with a greater IF. KEY POINTS: • The proportion of imaging specialist authors in non-imaging journals, though small, has increased significantly. • Marked differences are observed according to medical specialties and the reputation/impact factor of the journal. • Collaboration between imaging specialists and non-specialists is associated with publication in higher impact journals.

Performances and variability of CT radiomics for the prediction of microvascular invasion and survival in patients with HCC: a matter of chance or standardisation?

OBJECTIVES: To measure the performance and variability of a radiomics-based model for the prediction of microvascular invasion (MVI) and survival in patients with resected hepatocellular carcinoma (HCC), simulating its sequential development and application. METHODS: This study included 230 patients with 242 surgically resected HCCs who underwent preoperative CT, of which 73/230 (31.7%) were scanned in external centres. The study cohort was split into training set (158 patients, 165 HCCs) and held-out test set (72 patients, 77 HCCs), stratified by random partitioning, which was repeated 100 times, and by a temporal partitioning to simulate the sequential development and clinical use of the radiomics model. A machine learning model for the prediction of MVI was developed with least absolute shrinkage and selection operator (LASSO). The concordance index (C-index) was used to assess the value to predict the recurrence-free (RFS) and overall survivals (OS). RESULTS: In the 100-repetition random partitioning cohorts, the radiomics model demonstrated a mean AUC of 0.54 (range 0.44-0.68) for the prediction of MVI, mean C-index of 0.59 (range 0.44-0.73) for RFS, and 0.65 (range 0.46-0.86) for OS in the held-out test set. In the temporal partitioning cohort, the radiomics model yielded an AUC of 0.50 for the prediction of MVI, a C-index of 0.61 for RFS, and 0.61 for OS, in the held-out test set. CONCLUSIONS: The radiomics models had a poor performance for the prediction of MVI with a large variability in the model performance depending on the random partitioning. Radiomics models demonstrated good performance in the prediction of patient outcomes. CLINICAL RELEVANCE STATEMENT: Patient selection within the training set strongly influenced the performance of the radiomics models for predicting microvascular invasion; therefore, a random approach to partitioning a retrospective cohort into a training set and a held-out set seems inappropriate. KEY POINTS: • The performance of the radiomics models for the prediction of microvascular invasion and survival widely ranged (AUC range 0.44-0.68) in the randomly partitioned cohorts. • The radiomics model for the prediction of microvascular invasion was unsatisfying when trying to simulate its sequential development and clinical use in a temporal partitioned cohort imaged with a variety of CT scanners. • The performance of the radiomics models for the prediction of survival was good with similar performances in the 100-repetition random partitioning and temporal partitioning cohorts.

Semiautomatic Cone-Beam Computed Tomography Virtual Hepatic Volumetry for Intra-Arterial Therapies.

PURPOSE: To evaluate a software simulating the perfused liver volume from virtual selected embolization points on proximal enhanced cone-beam computed tomography (CT) liver angiography data set using selective cone-beam CT as a reference standard. MATERIALS AND METHODS: Seventy-eight selective/proximal cone-beam CT couples in 46 patients referred for intra-arterial liver treatment at 2 recruiting centers were retrospectively included. A reference selective volume (RSV) was calculated from the selective cone-beam CT by manual segmentation and was used as a reference standard. The virtual perfusion volume (VPV) was then obtained using Liver ASSIST Virtual Parenchyma software on proximal cone-beam CT angiography using the same injection point as for selective cone-beam CT. RSV and VPV were then compared as absolute, relative, and signed volumetric errors (ABSErr, RVErr, and SVErr, respectively), whereas their spatial correspondence was assessed using the Dice similarity coefficient. RESULTS: The software was technically successful in automatically computing VPV in 74 of 78 (94.8%) cases. In the 74 analyzed couples, the median RSV was not significantly different from the median VPV (394 mL [196-640 mL] and 391 mL [192-620 mL], respectively; P = .435). The median ABSErr, RVErr, SVErr, and Dice similarity coefficient were 40.9 mL (19.9-97.7 mL), 12.8% (5%-22%), 9.9 mL (-49.0 to 40.4 mL), and 80% (76%-84%), respectively. No significant ABSErr, RVErr, SVErr, and Dice similarity coefficient differences were found between the 2 centers (P = .574, P = .612, P = .416, and P = .674, respectively). CONCLUSIONS: Perfusion hepatic volumes simulated on proximal enhanced cone-beam CT using the virtual parenchyma software are numerically and spatially similar to those manually obtained on selective cone-beam CT.

The Safety and Effectiveness of Hepatic Transarterial Embolic Locoregional Therapy in Patients with Contraindications to Hepatectomy after Portal Vein Embolization.

The safety and effectiveness of hepatic transarterial embolic locoregional therapy (LRT) was assessed, including transarterial chemoembolization (TACE) and transarterial radioembolization (TARE), in patients who underwent portal vein embolization (PVE) before major hepatectomy in whom surgery was then contraindicated. Adverse events (AEs) were graded according to the Society of Interventional Radiology classification of AEs. Tumor response was assessed based on the Response Evaluation Criteria In Solid Tumors 1.1. Overall survival (OS) and progression-free survival (PFS) were estimated. Fifteen patients underwent 37 transarterial LRTs (25 TACEs, 11 TAREs, and 1 bland embolization), most (73%) with hepatocellular carcinoma. Eleven AEs occurred in 7 patients, including 2 Grade 3/5 (severe) and 2 Grade 4/5 (life-threatening) events. The best response was partial response in 4 (27%) and stable disease in 10 (66%) patients. The median OS and PFS were 42 (95% CI, 35-49 months) and 33 months (95% CI, 24-42 months), respectively. In conclusion, hepatic transarterial LRT can be considered as a therapeutic option in patients with contraindicated liver surgery after PVE.

Impact of COVID-19 on the management of hepatocellular carcinoma in a high-prevalence area: What's new 12 months later?

INTRODUCTION AND OBJECTIVES: The lockdown policy introduced in 2020 to minimize the spread of the COVID-19 pandemic, significantly affected the management and care of patients affected by hepatocellular carcinoma (HCC). The aim of this follow-up study was to determine the 12 months impact of the COVID-19 pandemic on the cohort of patients affected by HCC during the lockdown, within six French academic referral centers in the metropolitan area of Paris. MATERIALS AND METHODS: We performed a 12 months follow-up of the cross-sectional study cohort included in 2020 on the management of patients affected by HCC during the first six weeks of the COVID-19 pandemic (exposed), compared to the same period in 2019 (unexposed). Overall survival were compared between the groups. Predictors of mortality were analysed with Cox regression. RESULTS: From the initial cohort, 575 patients were included (n = 263 Exposed_COVID, n = 312 Unexposed_COVID). Overall and disease free survival at 12 months were 59.9 ± 3.2% vs 74.3 ± 2.5% (p<0.001) and 40.2 ± 3.5% vs 63.5 ± 3.1% (p<0.001) according to the period of exposure (Exposed_COVID vs Unexposed_COVID, respectively). Adjusted Cox regression revealed that the period of exposure (Exposed_COVID HR: 1.79, 95%CI (1.36, 2.35) p<0.001) and BCLC stage B, C and D (BCLC B HR: 1.82, 95%CI (1.07, 3.08) p = 0.027 - BCLC C HR: 1.96, 95%CI (1.14, 3.38) p = 0.015 - BCLC D HR: 3.21, 95%CI (1.76, 5.85) p<0.001) were predictors of death. CONCLUSIONS: Disruption of routine healthcare services because of the pandemic translated to reduced 1 year overall and disease-free survival among patients affected by HCC, in the metropolitan area of Paris, France.

Immunophenotypic and molecular characterization of pancreatic neuroendocrine tumors producing serotonin.

Serotonin producing pancreatic neuroendocrine tumors (SP-PanNET) account for 0.58-1.4% of all pancreatic neuroendocrine tumors (PanNET). They may present with atypical symptoms, such as acute pancreatitis and are often radiologically characterized by main pancreatic duct dilatation. SP-PanNET are well differentiated neuroendocrine tumors (NET) distinct from classical PanNET by atypical serotonin secretion and abundant dense stroma deposition, like serotonin producing ileal NET leading in some cases to difficulties to reliably distinguish SP-PanNET from ileal NET metastases. The biology and molecular profile of SP-PanNET remain poorly characterized and the cell of origin within the pancreas is unclear. To address these questions, we analyzed a large cohort of SP-PanNET by immunohistochemistry (n = 29; ATRX, DAXX, MENIN, Islet1, PAX6, PDX1, ARX, CDX2), whole genome copy number array (Oncoscan™) and a large NGS panel (NovoPM™) (n = 10), FISH (n = 13) and RNA sequencing (n = 24) together with 21 ileal NET and 29 nonfunctioning PanNET (NF-PanNET). These analyses revealed a unique genomic profile with frequent isolated loss of chromosome 1 (14 cases-61%) and few pathogenic mutations (KMT2C in 2 cases, ARID1A in 1 case). Unsupervised RNAseq-based clustering showed that SP-PanNET were closer to NF-PanNET than ileal NET with an exclusive beta cell-like signature. SP-PanNET showed TGF-ß pathway activation signatures associated with extracellular matrix remodeling and similar signature were reproduced in vitro when pancreatic stellate cells were exposed to serotonin. SP-PanNET immunohistochemical profile resemble that of ileal NET except for PDX1 and PAX6 expression to a lesser extend suggesting that these two markers may be useful to diagnose SP-PanNET. Taken together, this suggests that SP-PanNET are a very specific PanNET entity with a peculiar biology leading to the characteristic fibrotic aspect.

Liver surface nodularity on non-contrast MRI identifies advanced fibrosis in patients with NAFLD.

OBJECTIVES: To evaluate the diagnostic performance of liver surface nodularity (LSN) for the assessment of advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: We retrospectively analysed patients with pathologically proven NAFLD who underwent liver MRI. Demographic, clinical, and laboratory data (including FIB-4 scores) were gathered. The SAF score was used to assess NAFLD. MRI-proton density fat fraction (PDFF) and LSN were determined on pre-contrast MR sequences. ROC curve analysis was performed to evaluate the diagnostic performance of MRI-LSN for the diagnosis of advanced (F3-F4) liver fibrosis. RESULTS: The final population included 142 patients. Sixty-seven (47%) patients had non-alcoholic steatohepatitis (NASH), and 52 (37%) had advanced fibrosis. The median MRI-PDFF increased with the grades of steatosis: 8.1%, 18.1%, and 31% in S1, S2, and S3 patients, respectively (p < 0.001). The area under the ROC curve (AUC) of MRI-LSN ≥ 2.50 was 0.838 (95%CI 0.767-0.894, sensitivity 67.3%, specificity 88.9%, positive and negative predictive values 77.8% and 82.5%, respectively) for the diagnosis of advanced fibrosis. Combining FIB-4 and MRI-LSN correctly classified 103/142 (73%) patients. This was validated in an external cohort of 75 patients. CONCLUSIONS: MRI-LSN has good diagnostic performance in diagnosis of advanced fibrosis in NAFLD patients. A combination of FIB-4 and MRI-LSN derived from pre-contrast MRI could be helpful to detect advanced fibrosis. KEY POINTS: • MRI-LSN ≥ 2.5 was accurate for the diagnosis of advanced hepatic fibrosis in NAFLD patients. • The combination of FIB-4 and MRI-LSN improved the detection of advanced fibrosis. • MRI-LSN can be easily derived by unenhanced MRI sequences that are routinely acquired.

HCC advances in diagnosis and prognosis: Digital and Imaging.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. Understanding of the pathogenesis of HCC has significantly improved in the past few years due to advances in genetics, molecular biology and pathology. Several subtypes have been identified with different backgrounds and outcomes, leading to possible changes in disease management and challenging the role of imaging. Indeed, despite its pivotal role in the diagnostic workup, prognosis, and the decision-making process in patients with HCC, these recent developments are progressively redefining the role of imaging. First and most important, liver imaging is shifting from a purely qualitative to a quantitative paradigm, integrating quantitative imaging and radiomics in a digital era. Second, to improve patient management, imaging has gradually moved beyond tumor-centered assessment to include a broader evaluation of the liver and its function. This review describes and discusses these advances in the imaging for the diagnosis and prognosis of HCC.

Tumor Growth Rate to Predict the Outcome of Patients with Neuroendocrine Tumors: Performance and Sources of Variability.

INTRODUCTION: Tumor growth rate (TGR), percentage of change in tumor volume/month, has been previously identified as an early radiological biomarker for treatment monitoring in neuroendocrine tumor (NET) patients. We assessed the performance and reproducibility of TGR at 3 months (TGR3m) as a predictor factor of progression-free survival (PFS), including the impact of imaging method and reader variability. METHODS: Baseline and 3-month (±1 month) CT/MRI images from patients with advanced, grade 1-2 NETs were retrospectively reviewed by 2 readers. Influence of number of targets, tumor burden, and location of lesion on the performance of TGR3m to predict PFS was assessed by uni/multivariable Cox regression analysis. Agreement between readers was assessed by Lin's concordance coefficient (LCC) and kappa coefficient (KC). RESULTS: A total of 790 lesions were measured in 222 patients. Median PFS was 22.9 months. On univariable analysis, number of lesions (

Serotonin immunoreactive pancreatic neuroendocrine neoplasm associated with main pancreatic duct dilation: a recognizable entity with excellent long-term outcome.

OBJECTIVES: Dilatation of the main pancreatic duct (MPD) is rare in pancreatic neuroendocrine neoplasm (panNEN) and may be due to different mechanisms. We compared the imaging and pathological characteristics as well as the outcome after resection of positive (S+) and negative (S-) serotonin immunoreactive panNENs causing MPD dilatation. METHODS: This retrospective study included patients with panNEN, with MPD dilatation (≥ 4 mm) on preoperative CT/MRI and resected between 2005 and 2019. Clinical, radiological, and pathological features were compared between S+ and S- panNENs. Imaging features associated with S+ panNEN were identified using logistic regression analysis. The diagnostic performance of imaging for the differentiation of S+ and S- panNENs was assessed by ROC curve analysis. Recurrence-free survival (RFS) was compared between the two groups. RESULTS: The final population of 60 panNENs included 20/60 (33%) S+ panNENs. S+ panNENs were smaller (median 12.5 mm vs. 33 mm; p < 0.01), more frequently hyperattenuating/intense on portal venous phase at CT/MRI (95% vs. 25%, p < 0.01), and presented with more fibrotic stroma on pathology (60.7 ± 16% vs. 40.7 ± 12.8%; p < 0.01) than S- panNENs. Tumor size was the only imaging factor associated with S+ panNEN on multivariate analysis. A tumor size ≤ 20 mm had 95% sensitivity and 90% specificity for the diagnosis of S+ panNEN. Among 52 patients without synchronous liver metastases, recurrence occurred in 1/20 (5%) with S+ panNEN and 18/32 (56%) with S- panNEN (p < 0.01). Median RFS was not reached in S+ panNENs and was 31.3 months in S- panNENs (p < 0.01). CONCLUSIONS: In panNENs with MPD dilatation, serotonin positivity is associated with smaller size, extensive fibrotic stroma, and better long-term outcomes. KEY POINTS: • S+ panNENs showed a higher percentage of fibrotic stroma, higher microvessel density, and lower proliferation index (Ki-67) compared to S- panNENs. • Radiologically, S+ panNENs causing dilatation of the MPD were characterized by a small size (< = 20 mm) and a persistent enhancement on portal phase on both CT and MRI. • Patients with S+ panNENs presented with longer RFS when compared to those with S- panNENs.

Predictive factors of severe abdominal pain during and after transarterial chemoembolization for hepatocellular carcinoma.

OBJECTIVES: To prospectively assess the frequency of severe abdominal pain during and after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) using the visual analog scale (VAS), and to identify predictive factors. METHODS: Ninety-eight TACE performed in 80 patients (mean 65 ± 12 years old, 60 men) were consecutively and prospectively included. Abdominal pain was considered severe if the VAS ≥ 30/100 after treatment administration, or if opioid analgesic (grades 2-3) intake was required during hospitalization. Patient and tumor characteristics as well as technical factors associated with severe pain were identified by binary logistic regression. RESULTS: The criterion for severe pain was met in 41/98 (42%) of procedures (peri-procedural pain 30/98 [31%] and opioid consumption during hospitalization 24/98 [25%]). Multivariate analysis identified age (odds ratio [OR] = 0.943 (95% confidence interval 0.895-0.994), p = 0.029), cirrhosis (OR = 0.284 (0.083-0.971), p = 0.045), and alcoholic liver disease (OR = 0.081 (0.010-0.659), p = 0.019) as negative predictive factors of severe abdominal pain. Severe abdominal pain occurred in or after 1/13 (8%), 8/34 (24%), 22/41 (54%), and 10/10 (100%) TACE sessions when none, one, two, and three of the protective factors were absent, respectively (p < 0.001). The area under the ROC curve of the combination of factors for the prediction of severe abdominal pain was 0.779 (CI 0.687-0.871). CONCLUSION: Severe abdominal pain was frequent during and after TACE revealing a clinically relevant and underestimated problem. A predictive model based on three readily available clinical variables suggests that young patients without alcoholic liver disease or cirrhosis could benefit from reinforced analgesia. KEY POINTS: • Severe abdominal pain occurs in 43% of TACE for HCC. • Younger age, absence of cirrhosis, and absence of alcoholic liver disease were identified as independent predictive factors of severe abdominal pain. • A simple combination of the three abovementioned features helped predict the occurrence of severe abdominal pain.

Long-term Evolution of Hepatocellular Adenomas at MRI Follow-up.

Background Hepatocellular adenomas (HCAs) are rare benign liver tumors. Guidelines recommend continued surveillance of patients diagnosed with HCAs, but these guidelines are mainly based on small studies or expert opinion. Purpose To analyze the long-term evolution of HCAs, including solitary and multiple lesions, and to identify predictive features of progression with MRI. Materials and Methods In a retrospective study, patients diagnosed with pathologically proven solitary or multiple HCAs between January 2004 and December 2015 were included; ß-catenin-mutated HCAs and HCAs with foci of malignancy were considered to be at risk for progression. MRI examinations were analyzed, and tumor evolution was evaluated by using Response Evaluation Criteria in Solid Tumors, version 1.1. Student t, Mann-Whitney, χ2, Fisher exact, and McNemar tests were used, as appropriate. Results In total, 118 patients (mean age, 40 years ± 10 [standard deviation]; 108 women) were evaluated, including 41 with a solitary HCA (mean age, 40 years ± 14; 36 women) and 77 with multiple HCAs (mean age, 40 years ± 10; 72 women). At a median follow-up of 5 years, 37 of 41 (90%) patients with a solitary HCA and 55 of 77 (71%) patients with multiple HCAs showed stable or regressive disease. After resection of solitary HCAs, new lesions appeared in only two of 29 (7%) patients, both of whom had HCAs at risk of progression. In patients with multiple HCAs, hepatocyte nuclear factor 1α-inactivated HCAs showed a higher rate of progression compared with inflammatory HCAs (11 of 26 [42%] vs seven of 37 [19%], P = .04) despite lower use (28 of 32 patients [88%] vs 45 of 45 patients [100%]; P = .03) and shorter duration (mean, 12.0 years ± 7.5 vs 19.2 years ± 9.2; P = .001) of oral contraceptive intake. Conclusion Long-term MRI follow-up showed that 78% of hepatocellular adenomas had long-term stability or regression. After resection of solitary hepatocellular adenomas, new lesions occurred only in hepatocellular adenomas at risk of progression. Patients with multiple hepatocellular adenomas were more likely to show progressive disease, with hepatic nuclear factor 1α-inactivated hepatocellular adenomas being the most common subtype showing progression. © RSNA, 2020 Online supplemental material is available for this article.

New insights in the management of Hepatocellular Adenoma.

Hepatocellular adenoma (HCA) are benign liver tumours that may be complicated by haemorrhage or malignant transformation to hepatocellular carcinoma. Epidemiological data are fairly outdated, but it is likely to assume that the incidence has increased over the past decades as HCA are more often incidentally found due to the more widespread use of imaging techniques and the increased incidence of obesity. Various molecular subgroups have been described. Each of these molecular subgroups are defined by specific gene mutations and pathway activations. Additionally, they are all related to specific risk factors and show a various biological behaviour. These molecular subgroups may be identified using immunohistochemistry and molecular characterization. Contrast-enhanced MRI is the recommended imaging modality to analyse patients with suspected hepatocellular adenoma allowing to determine the subtype in up to 80%. Surgical resection remains to be the golden standard in treating HCA, although resection is deemed unnecessary in a large number of cases, as studies have shown that the majority of HCA will regress over time without complications such as haemorrhage or malignant transformation occurring. It is preferable to treat patients with suspected HCA in high volume centres with combined expertise of liver surgeons, hepatologists, radiologists and (molecular) pathologists.