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.

Noninvasive assessment of liver disease severity in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes.

BACKGROUND AND AIMS: We evaluated the diagnostic accuracy of simple, noninvasive tests (NITs) in NAFLD patients with type 2 diabetes (T2D). METHODS AND RESULTS: This was an individual patient data meta-analysis of 1780 patients with biopsy-proven NAFLD and T2D. The index tests of interest were FIB-4, NAFLD Fibrosis Score (NFS), aspartate aminotransferase-to-platelet ratio index, liver stiffness measurement (LSM) by vibration-controlled transient elastography, and AGILE 3+. The target conditions were advanced fibrosis, NASH, and fibrotic NASH(NASH plus F2-F4 fibrosis). The diagnostic performance of noninvasive tests. individually or in sequential combination, was assessed by area under the receiver operating characteristic curve and by decision curve analysis. Comparison with 2278 NAFLD patients without T2D was also made. In NAFLD with T2D LSM and AGILE 3+ outperformed, both NFS and FIB-4 for advanced fibrosis (area under the receiver operating characteristic curve:LSM 0.82, AGILE 3+ 0.82, NFS 0.72, FIB-4 0.75, aspartate aminotransferase-to-platelet ratio index 0.68; p < 0.001 of LSM-based versus simple serum tests), with an uncertainty area of 12%-20%. The combination of serum-based with LSM-based tests for advanced fibrosis led to a reduction of 40%-60% in necessary LSM tests. Decision curve analysis showed that all scores had a modest net benefit for ruling out advanced fibrosis at the risk threshold of 5%-10% of missing advanced fibrosis. LSM and AGILE 3+ outperformed both NFS and FIB-4 for fibrotic NASH (area under the receiver operating characteristic curve:LSM 0.79, AGILE 3+ 0.77, NFS 0.71, FIB-4 0.71; p < 0.001 of LSM-based versus simple serum tests). All noninvasive scores were suboptimal for diagnosing NASH. CONCLUSIONS: LSM and AGILE 3+ individually or in low availability settings in sequential combination after FIB-4 or NFS have a similar good diagnostic accuracy for advanced fibrosis and an acceptable diagnostic accuracy for fibrotic NASH in NAFLD patients with T2D.

Imaging of Pancreatic Ductal Adenocarcinoma: An Update on Recent Advances.

Pancreatic ductal carcinoma (PDAC) is one of the leading causes of cancer-related death worldwide. Computed tomography (CT) remains the primary imaging modality for diagnosis of PDAC. However, CT has limitations for early pancreatic tumor detection and tumor characterization so that it is currently challenged by magnetic resonance imaging. More recently, a particular attention has been given to radiomics for the characterization of pancreatic lesions using extraction and analysis of quantitative imaging features. In addition, radiomics has currently many applications that are developed in conjunction with artificial intelligence (AI) with the aim of better characterizing pancreatic lesions and providing a more precise assessment of tumor burden. This review article sums up recent advances in imaging of PDAC in the field of image/data acquisition, tumor detection, tumor characterization, treatment response evaluation, and preoperative planning. In addition, current applications of radiomics and AI in the field of PDAC are discussed.

Two-dimensional shear wave elastography predicts survival in advanced chronic liver disease.

OBJECTIVE: Liver stiffness measurement (LSM) is a tool used to screen for significant fibrosis and portal hypertension. The aim of this retrospective multicentre study was to develop an easy tool using LSM for clinical outcomes in advanced chronic liver disease (ACLD) patients. DESIGN: This international multicentre cohort study included a derivation ACLD patient cohort with valid two-dimensional shear wave elastography (2D-SWE) results. Clinical and laboratory parameters at baseline and during follow-up were recorded. LSM by transient elastography (TE) was also recorded if available. The primary outcome was overall mortality. The secondary outcome was the development of first/further decompensation. RESULTS: After screening 2148 patients (16 centres), 1827 patients (55 years, 62.4% men) were included in the 2D-SWE cohort, with median liver SWE (L-SWE) 11.8 kPa and a model for end stage liver disease (MELD) score of 8. Combination of MELD score and L-SWE predict independently of mortality (AUC 0.8). L-SWE cut-off at ≥20 kPa combined with MELD ≥10 could stratify the risk of mortality and first/further decompensation in ACLD patients. The 2-year mortality and decompensation rates were 36.9% and 61.8%, respectively, in the 305 (18.3%) high-risk patients (with L-SWE ≥20 kPa and MELD ≥10), while in the 944 (56.6%) low-risk patients, these were 1.1% and 3.5%, respectively. Importantly, this M10LS20 algorithm was validated by TE-based LSM and in an additional cohort of 119 patients with valid point shear SWE-LSM. CONCLUSION: The M10LS20 algorithm allows risk stratification of patients with ACLD. Patients with L-SWE ≥20 kPa and MELD ≥10 should be followed closely and receive intensified care, while patients with low risk may be managed at longer intervals.

Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis.

OBJECTIVE: Liver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Index (FIB-4) and NAFLD (non-alcoholic fatty liver disease) Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies. DESIGN: Individual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed individually and in sequential combinations. RESULTS: Data were included from 37 primary studies (n=5735; 45% women; median age: 54 years; median body mass index: 30 kg/m2; 33% had type 2 diabetes; 30% had advanced fibrosis). AUROCs of individual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs (<1.3; ≥2.67) followed by LSM-VCTE cut-offs (<8.0; ≥10.0 kPa) to rule-in or rule-out advanced fibrosis had sensitivity and specificity (95% CI) of 66% (63-68) and 86% (84-87) with 33% needing a biopsy to establish a final diagnosis. FIB-4 cut-offs (<1.3; ≥3.48) followed by LSM cut-offs (<8.0; ≥20.0 kPa) to rule out advanced fibrosis or rule in cirrhosis had a sensitivity of 38% (37-39) and specificity of 90% (89-91) with 19% needing biopsy. CONCLUSION: Sequential combinations of markers with a lower cut-off to rule-out advanced fibrosis and a higher cut-off to rule-in cirrhosis can reduce the need for liver biopsies.

Reliability Criteria of Two-Dimensional Shear Wave Elastography: Analysis of 4277 Measurements in 788 Patients.

BACKGROUND & AIMS: Two-dimensional shear wave elastography (2D-SWE) is an accurate method for the non-invasive evaluation of liver fibrosis. We aimed to determine the reliability criteria and the number of necessary reliable measurements for 2D-SWE. METHODS: 788 patients with chronic liver disease underwent liver biopsy and 2D-SWE examination in three centers. The 4277 2D-SWE measurements performed were 2:1 randomly divided into derivation (n = 2851) and validation (n = 1426) sets. Reliability criteria for a 2D-SWE measurement were defined in the derivation set from the intrinsic characteristics given by the device (mean liver stiffness, standard deviation, diameter of the region of interest), with further evaluation in the validation set. RESULTS: In the whole population of 4277 measurements, AUROC for bridging fibrosis was 0.825 ± 0.006 and AUROC for cirrhosis was 0.880 ± 0.006. Mean stiffness and coefficient of variation (CV) were independent predictors of bridging fibrosis or cirrhosis. From these two parameters, new criteria were derived to define a reliable 2D-SWE measurement: stiffness <8.8 kPa, or stiffness between 8.8-11.9 kPa with CV <0.25, or stiffness ≥12.0 kPa with CV <0.10. In the validation set, AUROC for bridging fibrosis was 0.830 ± 0.013 in reliable measurements vs 0.667 ± 0.031 in unreliable measurements (P < .001). AUROC for cirrhosis was 0.918±0.014 vs 0.714 ± 0.027, respectively (P < .001). The best diagnostic accuracy for a 2D-SWE examination was achieved from three reliable measurements. CONCLUSIONS: Reliability of a 2D-SWE measurement relies on the coefficient of variation and the liver stiffness level. A 2D-SWE examination should include three reliable measurements according to our new criteria.

Diagnostic Performance of Attenuation to Stage Liver Steatosis with MRI Proton Density Fat Fraction as Reference: A Prospective Comparison of Three US Machines.

Background US tools to quantify liver fat content have recently been made clinically available by different vendors, but comparative data on their accuracy are lacking. Purpose To compare the diagnostic performances of the attenuation parameters of US machines from three different manufacturers (vendors 1, 2, and 3) in participants who underwent liver fat quantification with the MRI-derived proton density fat fraction (PDFF). Materials and Methods From July 2020 to June 2021, consecutive participants with chronic liver disease were enrolled in this prospective single-center study and underwent MRI PDFF quantification (reference standard) and US on the same day. US was performed with two different machines from among three vendors assessed. Areas under the receiver operating characteristic curve (AUCs) for the staging of liver steatosis (MRI PDFF: ≥5.5% for grade ≥S1 and ≥15.5% for grade ≥S2) were calculated in test and validation samples and then compared between vendors in the study sample. Results A total of 534 participants (mean age, 60 years ± 13 [SD]; 320 men) were evaluated. Failure of measurements occurred in less than 1% of participants for all vendors. Correlation coefficients with the MRI PDFF were 0.71, 0.73, and 0.54 for the attenuation coefficients of vendors 1, 2, and 3, respectively. In the test sample, AUCs for diagnosis of steatosis grade S1 and higher and grade S2 and higher were 0.89 and 0.93 for vendor 1 attenuation, 0.88 and 0.92 for vendor 2 attenuation, and 0.79 and 0.79 for vendor 3 attenuation, respectively. In the validation sample, a threshold value of 0.65 for vendor 1 and 0.66 for vendor 2 yielded sensitivity of 77% and 84% and specificity of 78% and 85%, respectively, for diagnosis of grade S1 and higher. Vendor 2 attenuation had greater AUCs than vendor 3 attenuation (P = .001 and P = .003) for diagnosis of grade S1 and higher and grade S2 and higher, respectively, and vender 2 had greater AUCs for attenuation than vendor 1 for diagnosis of grade S2 and higher (P = .04). For all vendors, attenuation was not associated with liver stiffness (correlation coefficients <0.05). Conclusion To stage liver steatosis, attenuation coefficient accuracy varied among US devices across vendors when using MRI proton density fat fraction quantification as the reference standard, with some demonstrating excellent diagnostic performance and similar cutoff values. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Dubinsky in this issue.

Transient Versus Two-Dimensional Shear-Wave Elastography in a Multistep Strategy to Detect Advanced Fibrosis in NAFLD.

BACKGROUND AND AIMS: The combination of laboratory and elastography tests allows the accurate diagnosis of advanced liver fibrosis in patients with NAFLD. In this study, we compared the diagnostic performances of a two-step strategy (laboratory tests and vibration-controlled transient elastography [VCTE] or two-dimensional shear-wave elastography with SuperSonic Imagine [2D-SWE-SSI]) and the added value of a three-step strategy (laboratory tests and two elastography methods). APPROACH AND RESULTS: From a prospective registry, we retrospectively selected 577 consecutive patients with suspicion of NAFLD who underwent laboratory tests to calculate the Fibrosis-4 (FIB-4) score, liver stiffness evaluation by VCTE (M and XL probes) and 2D-SWE-SSI, and liver biopsy. The diagnostic performances and need for liver biopsy in unclassified patients for the diagnosis of advanced fibrosis (F ≥ 3) in multistep strategies were compared. The area under the curve of FIB-4, VCTE, and 2D-SWE-SSI was 0.74, 0.82, and 0.88, respectively. Using the same thresholds, the FIB-4/2D-SWE-SSI and FIB-4/VCTE diagnostic performances were comparable (sensitivity, 71.4% and 66%; specificity, 91.4% and 91.5%; and accuracy, 83.7% and 81.4%; all P = not significant). Conversely, more patients required liver biopsy after 2D-SWE-SSI (24.6% versus 15.3%, P < 0.001). Performing a second elastography technique in patients with unreliable or gray zone (between 8 and 10 kPa) results greatly decreased the need for liver biopsy (42/577, 7.3%). The diagnostic performances (accuracy, sensitivity, and specificity) of FIB-4/2D-SWE-SSI/VCTE and FIB-4/VCTE/2D-SWE-SSI were comparable (81.1%, 71.5%, and 87.9% versus 81.3%, 69.7%, and 89.5%, respectively; all P = not significant). CONCLUSIONS: Using the same cutoff values, 2D-SWE-SSI is as accurate as VCTE for advanced liver fibrosis diagnosis in NAFLD. The three-step strategy in selected patients strongly decreased the need for liver biopsy while maintaining excellent accuracy.

Comparison of extracellular and hepatobiliary MR contrast agents for the diagnosis of small HCCs.

BACKGROUND & AIMS: The aim of this study was to use a head-to-head nodule comparison to compare the performance of extracellular contrast agent MRI (ECA-MRI) with that of hepatobiliary contrast agent MRI (HBA-MRI) for the non-invasive diagnosis of small hepatocellular carcinomas (HCCs). METHODS: Between August 2014 and October 2017, 171 patients with cirrhosis, each with 1 to 3 nodules measuring 1-3 cm, were enrolled across 8 centers. All patients underwent both an ECA-MRI and an HBA-MRI within a month. A non-invasive diagnosis of HCC was made when a nodule exhibited arterial phase hyper-enhancement (APHE) with washout at the portal venous phase (PVP) and/or delayed phase (DP) for ECA-MRI, or the PVP and/or HB phase (HBP) for HBA-MRI. The gold standard was defined by using a previously published composite algorithm. RESULTS: A total of 225 nodules, of which 153 were HCCs and 72 were not, were included. The sensitivites of both MRI techniques were similar. Specificity was 83.3% (95% CI 72.7-91.1) for ECA-MRI and 68.1% (95% CI 56.0-78.6) for HBA-MRI. In terms of HCC diagnosis on ECA-MRI, 138 nodules had APHE, 84 had washout at PVP, and 104 at DP; on HBA-MRI, 128 nodules had APHE, 71 had washout at PVP, and 99 at HBP. For nodules 2-3 cm in size, sensitivity and specificity were similar between the 2 approaches. For nodules 1-2 cm in size, specificity dropped to 66.1% (95% CI 52.2-78.2) for HBA-MRI vs. 85.7% (95% CI 73.8-93.6) for ECA-MRI. CONCLUSIONS: HBA-MRI specificity is lower than that of ECA-MRI for diagnosing small HCCs in patients with cirrhosis. These results raise the question of the proper use of HBA-MRI in algorithms for the non-invasive diagnosis of small HCCs. LAY SUMMARY: There are 2 magnetic resonance imaging (MRI)-based approaches available for the non-invasive diagnosis of hepatocellular carcinoma (HCC), using either extracellular or hepatobiliary contrast agents. The current results showed that the sensitivity of MRI with hepatobiliary contrast agents was similar to that with extracellular contrast agents, but the specificity was lower. Thus, hepatobiliary contrast agent-based MRI, although detailed in international guidelines, should be used with caution for the non-invasive diagnosis of HCC. CLINICAL TRIAL NUMBER: NCT00848952.

Agreement Between 2-Dimensional Shear Wave and Transient Elastography Values for Diagnosis of Advanced Chronic Liver Disease.

BACKGROUND & AIMS: Inter-platform variation in liver stiffness evaluation (LSE) could hinder dissemination and clinical implementation of new ultrasound methods. We aimed to determine whether measurements of liver stiffness by bi-dimensional shear wave elastography (2D-SWE) with a Supersonic Imagine apparatus are comparable to those made by vibration-controlled transient elastography (VCTE). METHODS: We collected data from 1219 consecutive patients with chronic liver disease who underwent LSE by VCTE and 2D-SWE (performed by blinded operators), on the same day, at a single center in France from September 2011 through June 2019. We assessed the ability of liver stiffness value distributions and 2D-SWE performances to identify patients with compensated advanced chronic liver disease (cACLD) according to the Baveno VI criteria, based on VCTE cut-off values. RESULTS: VCTE and 2D-SWE values correlated (Pearson's correlation coefficient, 0.882; P < .0001; Lin concordance coefficient, 0.846; P < .0001). The median stiffness values were 6.7 kPa with VCTE (interquartile range, 4.8-11.6 kPa) and 7.1 kPa with 2D-SWE (interquartile range, 5.4-11.1 kPa) (P = .736). 2D-SWE values were slightly higher in the low percentiles and lower in the high percentiles; the best match with VCTE values were at approximately 7-9 kPa. The area under the curve of 2D-SWE for identifying of VCTE values below 10 was 0.964 (95% CI, 0.952-0.976) and for VCTE values above 15 kPa was 0.976 (95% CI, 0.963-0.988), with Youden index-associated cut-off values of 9.5 and 13kPa and best accuracy cut-off values of 10 kPa and 14 kPa, respectively. A 2D-SWE cut-off value of 10 kPa detected VCTE values below 10k Pa with 92% sensitivity, 87% specificity, and 91% accuracy. CONCLUSIONS: Measurement of liver stiffness by VCTE or 2D-SWE produces comparable results. 2D-SWE accurately identifies patients with cACLD according to the Baveno VI criteria based on VCTE cut-off values. A 10 kPa 2D-SWE cut-off value can be used to rule out cACLD.

Quantification of liver fat content in liver and primary liver lesions using triple-echo-gradient-echo MRI.

OBJECTIVES: To quantify and compare the fat fraction of background liver and primary liver lesions using a triple-echo-gradient-echo sequence. M&M: This IRB-approved study included 128 consecutive patients who underwent a liver MRI for lesion characterization. Fat fraction from the whole lesion volume and the normal liver parenchyma were computed from triple-echo (consecutive in-phase, opposed-phase, in-phase echo times) sequence. RESULTS: Forty-seven hepatocellular carcinoma (HCCs), 25 hepatocellular adenomas (HCAs), and 56 focal nodular hyperplasia (FNH) were included. The mean intralesional fat fraction for various lesions was 7.1% (range, 0.5-23.6; SD, 5.6) for HCAs, 5.7% (range, 0.8-14; SD, 2.9) for HCCs, and 2.3% (range, 0.8-10.3; SD, 1.9) for FNHs (p = 0.6 for HCCs vs HCA, p < 0.001 for FNH vs HCCs or HCA). A fat fraction threshold of 2.7% enabled distinction between HCA and FNH with a sensitivity of 80% and a specificity of 77%. The mean normal liver parenchyma fat fraction was lower than the intralesional fat fraction in the HCC group (p = 0.04) and higher in the FNH group (p = 0.001), but not significantly different in the HCA group (p = 0.51). CONCLUSION: Triple-echo-gradient-echo is a feasible technique to quantify fat fraction of background liver and primary liver lesions. Intralesional fat fraction obtained from lesion whole volume is greater for HCCs and HCA compared to FNH. When trying to distinguish FNH and HCA, an intralesional fat fraction < 2.7% may orient toward the diagnosis of FNH. KEY POINTS: • Triple-echo technique is feasible to quantify intralesional fat fraction of primary liver lesions. • Whole volume intralesional fat fraction is greater for HCCs and HCA compared to FNH. • An intralesional fat fraction < 2.7% may orient toward the diagnosis of FNH.

Learning curve of liver stiffness measurement using a new hybrid machine composed of transient elastography interfaced with ultrasound.

OBJECTIVES: To assess the learning curve for performing reliable liver stiffness measurements using a new hybrid machine composed of transient elastography (TE) interfaced with an ultrasound device for radiographers and radiologists with different levels of expertise in ultrasound imaging. METHODS: Ten novice operators who had never performed TE measurements were prospectively evaluated from April to October 2018: senior radiologists, young radiologists, fellows, radiographers, and residents, with different levels of experience in abdominal ultrasound imaging. All operators had a short theoretical training followed by a training session under supervision in three patients. Then, each operator had to perform TE in 50 consecutive patients with chronic liver disease, using beforehand ultrasound examination to select measurement area in the right liver lobe, and if needed, the XL probe. Percentages of failures and reliable measurements were compared. RESULTS: The rates of failures of measurements, poorly reliable, reliable, and very reliable results, were of 4.2% (21/500), 2.4% (12/500), 47.6% (238/500), and 45.8% (229/500), respectively. The rates of reliable plus very reliable results were excellent, ranging from 91 to 96% among all the subgroups. The rates of very reliable, reliable, and unreliable results did not differ between operator subgroups and especially between junior radiologists, senior radiologists, and radiographers. No breaking point was observed in the interquartile range/median values over time. CONCLUSION: TE interfaced with ultrasound in this hybrid machine presents no learning curve effect. After a short initial training session, a novice observer is able to perform high rates of reliable and very reliable TE measurements. KEY POINTS: • When performing liver stiffness measurements using a new hybrid machine composed of transient elastography interfaced with ultrasound, the rate of failures of measurements is very low, below 5%. • After a short training session and using ultrasound planning, a novice operator, whatever its expertise in ultrasound imaging, is capable of performing high rates of reliable and very reliable measurements. • No learning curve is needed for performing reliable liver stiffness measurements using this new hybrid machine.

Criteria to Determine Reliability of Noninvasive Assessment of Liver Fibrosis With Virtual Touch Quantification.

BACKGROUND & AIMS: Virtual Touch Quantification (VTQ) evaluates liver fibrosis in patients with chronic liver diseases by measuring shear wave speed in the liver. We aimed to determine the reliability criteria of VTQ examination. METHODS: We performed a prospective study of 1094 patients with chronic liver disease from November 2009 through October 2016 at Angers University Hospital, and between April 2010 and May 2015 at Bordeaux University Hospital, in France. All patients underwent liver biopsy analysis (reference standard), and VTQ examination was made by experienced operators on the same day, or no more than 3 months before or afterward. Advanced liver fibrosis was defined as fibrosis stage F ≥ 3 according to the scoring system of the Nonalcoholic Steatohepatitis Clinical Research Network, or fibrosis stage F ≥ 2 according to the Metavir scoring system. The diagnostic accuracy of VTQ in detection of advanced fibrosis or cirrhosis was assessed using the area under the receiver operating characteristic (AUROC) and the rate of correctly classified patients. Reliability criteria were defined from the intrinsic characteristics of VTQ examination, which were shown to influence the diagnostic accuracy. RESULTS: VTQ identified patients with advanced fibrosis with an AUROC of 0.773 ± 0.014 and correctly classified 72.0% of patients using a diagnostic cut-off value of 1.37 m/s. VTQ identified patients with cirrhosis with an AUROC value of 0.839 ± 0.014 and correctly classified 78.4% of patients using a cut-off value of 1.87 m/s. The reliability of VTQ decreased with an increasing ratio of interquartile range/median (IQR/M) in patients with intermediate-high VTQ results. We defined 3 reliability categories for VTQ: unreliable (IQR/M ≥0.35 with VTQ result ≥1.37 m/s), reliable (IQR/M ≥0.35 with VTQ result <1.37 m/s or IQR/M 0.15-0.34), and very reliable (IQR/M <0.15). For advanced fibrosis, VTQ correctly classified 57.8% of patients in the unreliable group, 73.7% of patients in the reliable group, and 80.9% of patients in the very reliable group (P < .001); for cirrhosis, these values were 50.0%, 83.4%, and 92.6%, respectively (P < .001). Of the VTQ examinations made, 21.4% were unreliable, 55.0% were reliable, and 23.6% were very reliable. The skin-liver capsule distance was independently associated with an unreliable VTQ examination, which occurred in 52.7% of patients with a distance of 30 mm or more. CONCLUSIONS: In a study to determine the reliability of VTQ findings, compared with results from biopsy analysis, we assigned VTQ examinations to 3 categories (unreliable, reliable, and very reliable). VTQ examinations with IQR/M ≥0.35 and ≥1.37 m/s had very low diagnostic accuracy. Our reliability criteria for liver fibrosis assessment with VTQ will help physicians to accurately evaluate the severity of chronic liver diseases and monitor their progression.

Assessment of biopsy-proven liver fibrosis by two-dimensional shear wave elastography: An individual patient data-based meta-analysis.

Two-dimensional shear wave elastography (2D-SWE) has proven to be efficient for the evaluation of liver fibrosis in small to moderate-sized clinical trials. We aimed at running a larger-scale meta-analysis of individual data. Centers which have worked with Aixplorer ultrasound equipment were contacted to share their data. Retrospective statistical analysis used direct and paired receiver operating characteristic and area under the receiver operating characteristic curve (AUROC) analyses, accounting for random effects. Data on both 2D-SWE and liver biopsy were available for 1,134 patients from 13 sites, as well as on successful transient elastography in 665 patients. Most patients had chronic hepatitis C (n = 379), hepatitis B (n = 400), or nonalcoholic fatty liver disease (n = 156). AUROCs of 2D-SWE in patients with hepatitis C, hepatitis B, and nonalcoholic fatty liver disease were 86.3%, 90.6%, and 85.5% for diagnosing significant fibrosis and 92.9%, 95.5%, and 91.7% for diagnosing cirrhosis, respectively. The AUROC of 2D-SWE was 0.022-0.084 (95% confidence interval) larger than the AUROC of transient elastography for diagnosing significant fibrosis (P = 0.001) and 0.003-0.034 for diagnosing cirrhosis (P = 0.022) in all patients. This difference was strongest in hepatitis B patients. CONCLUSION: 2D-SWE has good to excellent performance for the noninvasive staging of liver fibrosis in patients with hepatitis B; further prospective studies are needed for head-to-head comparison between 2D-SWE and other imaging modalities to establish disease-specific appropriate cutoff points for assessment of fibrosis stage. (Hepatology 2018;67:260-272).

An In Vitro Evaluation of Four Types of Drug-Eluting Embolics Loaded with Idarubicin.

PURPOSE: This study compared loading, elution, and stability of drug-eluting embolic beads (DEBs) loaded with idarubicin. MATERIALS AND METHODS: DC Bead (100-300 µm), HepaSphere (30-60 µm), LifePearl (200 µm), and Tandem (100 µm) DEBs were loaded with 5 mg/mL idarubicin. Loading, elution, diameter changes, loading stability over 2 weeks in storage, and time in suspension were determined for each of the DEBs. RESULTS: Loading of more than 99% of idarubicin was achieved within 15 minutes for LifePearl, DC Bead, and Tandem beads. LifePearl, DC Bead, HepaSphere, and Tandem beads eluted 75% of the total idarubicin released in 13, 24, 42, and 91 minutes, respectively. In vitro elution was completed in 2 hours with 73% ± 3%, 74% ± 3%, 65% ± 6%, and 7% ± 0% of the loaded idarubicin eluted for LifePearl, DC Bead, HepaSphere, and Tandem, respectively. Statistically significant differences were observed at every time point between at least 2 of the products. Overall, in vitro idarubicin elution was rapid and nearly complete for LifePearl, DC Bead, and HepaSphere beads but was minimal and slow from Tandem beads. The average diameter of DEBs after loading was reduced by 5% for LifePearl, whereas it was increased by 9% and 1% for DC Bead and Tandem, respectively. After loading, time in suspension was 11 ± 4 and 10 ± 2 minutes for LifePearl and HepaSphere, respectively, whereas DC Bead and Tandem beads were held in suspension for greater than 20 minutes. CONCLUSIONS: Although all 4 DEBs loaded idarubicin within 15 minutes with minimal changes in diameter, the elution amounts, rates of release, and time in suspension varied.

Microvascular invasion is a major prognostic factor after pancreatico-duodenectomy for adenocarcinoma.

BACKGROUND: Microvascular invasion (MVI) has been proved to be poor prognostic factor in many cancers. To date, only one study published highlights the relationship between this factor and the natural history of pancreatic cancer. The aim of this study was to assess the impact of MVI, on disease-free survival (DFS) and overall survival (OS), after pancreatico-duodenectomy (PD) for pancreatic head adenocarcinoma. Secondarily, we aim to demonstrate that MVI is the most important factor to predict OS after surgery compared with resection margin (RM) and lymph node (LN) status. MATERIALS AND METHODS: Between January 2015 and December 2017, 158 PD were performed in two hepato-bilio-pancreatic (HBP) centers. Among these, only 79 patients fulfilled the inclusion criteria of the study. Clinical-pathological data and outcomes were retrospectively analyzed from a prospectively maintained database. RESULTS: Of the 79 patients in the cohort, MVI was identified in 35 (44.3%). In univariate analysis, MVI (P = .012 and P < .0001), RM (P = .023 and P = .021), and LN status (P < .0001 and P = .0001) were significantly associated with DFS and OS. A less than 1 mm margin clearance did not influence relapse (P = .72) or long-term survival (P = .48). LN ratio > 0.226 had a negative impact on OS (P = .044). In multivariate analysis, MVI and RM persisted as independent prognostic factors of DFS (P = .0075 and P = .0098, respectively) and OS (P < .0001 and P = .0194, respectively). Using the likelihood ratio test, MVI was identified as the best fit to predict OS after PD for ductal adenocarcinomas compared with the margin status model (R0 vs R1) (P = .0014). CONCLUSION: The MVI represents another major prognostic factor determining long-term outcomes.

Intra-arterial idarubicin_lipiodol without embolisation in hepatocellular carcinoma: The LIDA-B phase I trial.

BACKGROUND & AIMS: Idarubicin shows high cytotoxicity against hepatocellular carcinoma (HCC) cells, a high hepatic extraction ratio, and high lipophilicity leading to stable emulsions with lipiodol. A dose-escalation phase I trial of idarubicin_lipiodol (without embolisation) was conducted in patients with cirrhotic HCC to estimate the maximum-tolerated dose (MTD) and to assess the safety, efficacy, and pharmacokinetics of the drug, and the health-related quality of life achieved by patients. METHODS: Patients underwent two sessions of treatment with a transarterial idarubicin_lipiodol emulsion without embolisation. The idarubicin dose was escalated according to a modified continuous reassessment method. The MTD was defined as the dose closest to that causing dose-limiting toxicity (DLT) in 20% of patients. RESULTS: A group of 15 patients were enrolled, including one patient at 10 mg, four patients at 15 mg, seven patients at 20 mg, and three patients at 25 mg. Only two patients experienced DLT: oedematous ascitic decompensation and abdominal pain at 20 and 25 mg, respectively. The calculated MTD of idarubicin was 20 mg. The most frequent grade ≥3 adverse events were biological. One month after the second session, the objective response rate was 29% (complete response, 0%; partial response, 29%) based on modified Response Evaluation Criteria In Solid Tumours. The median time to progression was 5.4 months [95% confidence limit (CI) 3.0-14.6 months] and median overall survival was 20.6 months (95% CI 5.7-28.7 months). Pharmacokinetic analysis of idarubicin showed that the mean Cmax of idarubicin after intra-arterial injection of the idarubicin-lipiodol emulsion is approximately half the Cmax after intravenous administration. Health-related quality of life results confirmed the good safety results associated with use of the drug. CONCLUSIONS: The MTD of idarubicin was 20 mg after two chemolipiodolisation sessions. Encouraging safety results, and patient responses and survival were observed. A phase II trial has been scheduled. LAY SUMMARY: There is a need for transarterial regimens that improve the responses and survival of patients with unresectable HCC. In this phase I trial, we showed that two sessions of treatment with a transarterial idarubicin_lipiodol emulsion without embolisation was well tolerated and gave promising efficacy in terms of tumour control and patient survival.

Pancreatic Adenocarcinoma Staging in the Era of Preoperative Chemotherapy and Radiation Therapy.

Pancreatic ductal adenocarcinoma (PDA) remains among the most challenging malignancies to treat. At diagnosis, the tumor often already extends beyond the confines of the pancreas, spreading to an extent such that primary surgery with curative intent is very rarely feasible. Considerable momentum is now being given to a treatment strategy involving neoadjuvant chemotherapy or chemotherapy and radiation therapy in patients with nonmetastatic PDA. The main advantage of this strategy is better selection of patients likely to benefit from curative-intent surgery through the achievement of negative resection margins. Patients with rapidly progressive disease are identified and are spared ineffective surgery with its attendant morbidity. Neoadjuvant therapy can downstage tumors classified as locally advanced at initial imaging studies to resectable tumors. However, the imaging study evaluation of the response to neoadjuvant therapy is extremely complex. Thus, the diagnostic performance of imaging studies is not sufficient to ensure the accurate selection of patients in whom negative-margin resection is likely to be achieved. More specifically, standard criteria for predicting vascular invasion, based on the amount of tumor-vessel contact, are not valid after neoadjuvant therapy. ©RSNA, 2018.

Tumor Targeting and Three-Dimensional Voxel-Based Dosimetry to Predict Tumor Response, Toxicity, and Survival after Yttrium-90 Resin Microsphere Radioembolization in Hepatocellular Carcinoma.

PURPOSE: To identify predictive factors of tumor response, progression-free survival (PFS), overall survival (OS), and toxicity using three-dimensional (3D) voxel-based dosimetry in patients with intermediate and advanced stage hepatocellular carcinoma (HCC) treated by yttrium-90 (90Y) resin microspheres radioembolization (RE). MATERIALS AND METHODS: From February 2012 to December 2015, 45 90Y resin microspheres RE procedures were performed for HCC (Barcelona Clinic Liver Cancer stage B/C; n = 15/30). Area under the dose-volume histograms (AUDVHs) were calculated from 3D voxel-based dosimetry to measure 90Y dose deposition. Factors associated with tumor control (ie, complete/partial response or stable disease on Modified Response Evaluation Criteria in Solid Tumors) at 6 months were investigated. PFS and OS analyses were performed (Kaplan-Meier). Toxicity was assessed by occurrence of radioembolization-induced liver disease (REILD). RESULTS: Tumor control rate was 40.5% (17/42). Complete tumor targeting (odds ratio = 36.97; 95% confidence interval, 1.83-747; P < .001) and AUDVHtumor (odds ratio = 1.027; 95% confidence interval, 1.002-1.071; P = .033) independently predicted tumor control. AUDVHtumor ≥ 61 Gy predicted tumor control with 76.5% sensitivity and 75% specificity. PFS and OS in patients with incomplete tumor targeting were significantly shorter than in patients with complete tumor targeting (median PFS, 2.7 months [range, 0.8-4.6 months] vs 7.9 months [range, 2.1-39.5 months], P < .001; median OS, 4.5 months [range, 1.4-23 months] vs 19.2 months [range, 2.1-46.9 months], P < .001). Patients with incomplete tumor targeting and AUDVHtumor < 61 Gy, incomplete tumor targeting and AUDVHtumor > 61 Gy, complete tumor targeting and AUDVHtumor < 61 Gy, and AUDVHtumor > 61 Gy had median PFS of 2.7, 1.8, 6.3, and 12.1 months (P < .001). REILD (n = 4; 9.5%) was associated with higher dose delivered to normal liver (P = .04). CONCLUSIONS: Complete tumor targeting and 90Y dose to tumor are independent factors associated with tumor control and clinical outcomes.

Liver chemoembolization of hepatocellular carcinoma using TANDEM® microspheres.

Transarterial chemoembolization (TACE) combines intra-arterial delivery of a chemotherapeutic agent with selective embolization to obtain a synergistic effect. TACE is recognized as the standard treatment of hepatocellular carcinoma patients at an intermediate stage. If conventional TACE, defined as the injection of an emulsion of a drug with ethiodized oil, still has a role to play, the development of drug-eluting beads has allowed many improvements and optimization of the technique. TANDEM® microspheres are second-generation drug-loadable microspheres. This device raised a special interest due to its tightly calibrated spherical microspheres, with small sizes down to 40 µm available. In this review, we describe the technical characteristics of these microspheres, analyze the scientific literature and hypothesize on the future perspectives.