Performance of LI-RADS category 5 vs combined categories 4 and 5: a systemic review and meta-analysis.

OBJECTIVE: Computed tomography (CT)/magnetic resonance imaging (MRI) Liver Imaging Reporting and Data System (LI-RADS, LR) category 5 has high specificity and modest sensitivity for diagnosis of hepatocellular carcinoma (HCC). The purpose of this study was to compare the diagnostic performance of LR-5 vs combined LR-4 and LR-5 (LR-4/5) for HCC diagnosis. METHODS: MEDLINE and EMBASE databases through January 03, 2023 were searched for studies reporting the performance of LR-5 and combined LR-4/5 for HCC diagnosis, using CT/MRI LI-RADS version 2014, 2017, or 2018. A bivariate random-effects model was used to calculate the pooled per-observation diagnostic performance. Subgroup analysis was performed based on imaging modalities and type of MRI contrast material. RESULTS: Sixty-nine studies (15,108 observations, 9928 (65.7%) HCCs) were included. Compared to LR-5, combined LR-4/5 showed significantly higher pooled sensitivity (83.0% (95% CI [80.3-85.8%]) vs 65.7% (95% CI [62.4-69.1%]); p < 0.001), lower pooled specificity (75.0% (95% CI [70.5-79.6%]) vs 91.7% (95% CI [90.2-93.1%]); p < 0.001), lower pooled positive likelihood ratio (3.60 (95% CI [3.06-4.23]) vs 6.18 (95% CI [5.35-7.14]); p < 0.001), and lower pooled negative likelihood ratio (0.22 (95% CI [0.19-0.25]) vs 0.38 (95% CI [0.35-0.41]) vs; p < 0.001). Similar results were seen in all subgroups. CONCLUSIONS: Our meta-analysis showed that combining LR-4 and LR-5 would increase sensitivity but decrease specificity, positive likelihood ratio, and negative likelihood ratio. These findings may inform management guidelines and individualized management. CLINICAL RELEVANCE STATEMENT: This meta-analysis estimated the magnitude of changes in the sensitivity and specificity of imaging criteria when LI-RADS categories 4 and 5 were combined; these findings can inform management guidelines and individualized management. KEY POINTS: There is no single worldwide reporting system for liver imaging, partly due to regional needs. Combining LI-RADS categories 4 and 5 increased sensitivity and decreased specificity and positive and negative likelihood ratios. Changes in the sensitivity and specificity of imaging criteria can inform management guidelines and individualized management.

Liver Imaging Reporting and Data System version 2018 category 5 for diagnosing hepatocellular carcinoma: an updated meta-analysis.

OBJECTIVE: We performed an updated meta-analysis to determine the diagnostic performance of Liver Imaging Reporting and Data System (LI-RADS, LR) 5 category for hepatocellular carcinoma (HCC) using LI-RADS version 2018 (v2018), and to evaluate differences by imaging modalities and type of MRI contrast material. METHODS: The MEDLINE and Embase databases were searched for studies reporting the performance of LR-5 using v2018 for diagnosing HCC. A bivariate random-effects model was used to calculate the pooled per-observation sensitivity and specificity. Subgroup analysis was performed based on imaging modalities and type of MRI contrast material. RESULTS: Forty-eight studies qualified for the meta-analysis, comprising 9031 patients, 10,547 observations, and 7216 HCCs. The pooled per-observation sensitivity and specificity of LR-5 for diagnosing HCC were 66% (95% CI, 61-70%) and 91% (95% CI, 89-93%), respectively. In the subgroup analysis, MRI with extracellular agent (ECA-MRI) showed significantly higher pooled sensitivity (77% [95% CI, 70-82%]) than CT (66% [95% CI, 58-73%]; p = 0.023) or MRI with gadoxetate (Gx-MRI) (65% [95% CI, 60-70%]; p = 0.001), but there was no significant difference between ECA-MRI and MRI with gadobenate (gadobenate-MRI) (73% [95% CI, 61-82%]; p = 0.495). Pooled specificities were 88% (95% CI, 80-93%) for CT, 92% (95% CI, 86-95%) for ECA-MRI, 93% (95% CI, 91-95%) for Gx-MRI, and 91% (95% CI, 84-95%) for gadobenate-MRI without significant differences (p = 0.084-0.803). CONCLUSIONS: LI-RADS v2018 LR-5 provides high specificity for HCC diagnosis regardless of modality or contrast material, while ECA-MRI showed higher sensitivity than CT or Gx-MRI. CLINICAL RELEVANCE STATEMENT: Refinement of the criteria for improving sensitivity while maintaining high specificity of LR-5 for HCC diagnosis may be an essential future direction. KEY POINTS: • The pooled per-observation sensitivity and specificity of LR-5 for diagnosing HCC using LI-RADSv2018 were 66% and 91%, respectively. • ECA-MRI showed higher sensitivity than CT (77% vs 66%, p = 0.023) or Gx-MRI (77% vs 65%, p = 0.001). • LI-RADS v2018 LR-5 provides high specificity (88-93%) for HCC diagnosis regardless of modality or contrast material type.

Percentages of Hepatocellular Carcinoma in LI-RADS Categories with CT and MRI: A Systematic Review and Meta-Analysis.

Background The Liver Imaging Reporting and Data System (LI-RADS) CT and MRI algorithm applies equally to CT, MRI with extracellular contrast agents (ECA-MRI), and MRI with gadoxetate (Gx-MRI). Purpose To estimate pooled percentages of hepatocellular carcinoma (HCC) and overall malignancy for each LI-RADS category with CT and MRI. Materials and Methods MEDLINE and EMBASE databases were searched for research articles (January 2014-April 2021) reporting the percentages of observations in each LI-RADS category with use of versions 2014, 2017, or 2018. Study design, population characteristics, imaging modality, reference standard, and numbers of HCC and non-HCC malignancies in each category were recorded. A random-effects model evaluated the pooled percentage of HCC and overall malignancy for each category. Results There were 49 studies with 9620 patients and a total 11 562 observations, comprising 7921 HCCs, 1132 non-HCC malignancies, and 2509 benign entities. No HCC or non-HCC malignancies were reported with any modality in the LR-1 category. The pooled percentages of HCC for CT, ECA-MRI, and Gx-MRI, respectively, were 10%, 6%, and 1% for LR-2 (P = .16); 48%, 31%, and 38% for LR-3 (P = .42); 76%, 64%, and 77% for LR-4 (P = .62); 96%, 95%, and 96% for LR-5 (P = .76); 88%, 76%, and 78% for LR-5V or LR-TIV (tumor in vein) (P = .42); and 20%, 30%, and 35% for LR-M (P = .32). Most LR-M (93%-100%) and LR-5V or LR-TIV (99%-100%) observations were malignant, regardless of modality. Conclusion There was no difference in percentages of hepatocellular carcinoma and overall malignancy between CT, MRI with extracellular contrast agents, and MRI with gadoxetate for any Liver Imaging Reporting and Data System categories. © RSNA, 2023 Supplemental material is available for this article See also the editorial by Ronot in this issue.

Interobserver Variability and Diagnostic Performance in Predicting Malignancy of Pancreatic Intraductal Papillary Mucinous Neoplasm with MRI.

Background The 2017 international consensus guidelines for intraductal papillary mucinous neoplasm (IPMN) of the pancreas are widely used. Purpose To evaluate the interobserver agreement and diagnostic performance of MRI assessment in predicting the malignant potential of IPMN according to radiologists' experience. Materials and Methods This multicenter retrospective study included 100 patients with pathologically proven pancreatic IPMN (77 patients with surgery, 23 patients with biopsy) who underwent contrast-enhanced MRI between 2016 and 2021. Eight post-fellowship radiologists (four more-experienced [8-20 years] and four less-experienced [1-4 years] reviewers) evaluated MRI for high-risk stigmata and worrisome features identified by the most recent 2017 guidelines. Interobserver agreement was determined using Fleiss κ statistics according to radiologist experience. The diagnostic performance for malignant IPMN was assessed using receiver operating characteristic curve analysis. Results Among 100 patients (mean age, 66 years ± 10 [SD]; 57 men), 52 (52%) had malignant IPMN. For high-risk stigmata, interobserver agreement was substantial for main pancreatic duct size of at least 10 mm (κ = 0.78; 95% CI: 0.75, 0.82), enhancing mural nodule of at least 5 mm (κ = 0.70: 95% CI: 0.66, 0.74), and at least one high-risk stigmata (κ = 0.73: 95% CI: 0.69, 0.76). The worrisome features showed fair to substantial interobserver agreement (κ range, 0.22-0.80). More-experienced reviewers demonstrated better agreement in the assessment of at least one high-risk stigmata than less-experienced reviewers (κ = 0.77 vs κ = 0.69, P < .001). The overall diagnostic performance of each reviewer was good for the prediction of malignant pancreatic IPMN (area under the receiver operating characteristic curve [AUC] range, 0.77-0.84; median AUC, 0.82), with substantial agreement (κ = 0.76). Conclusion The 2017 international consensus guidelines enabled good diagnostic performance and substantial interobserver agreement for high-risk stigmata but not worrisome features on the evaluation of the malignant pancreatic IPMN using MRI. Agreement tended to be better among more-experienced reviewers than among less-experienced reviewers. © RSNA, 2023 Supplemental material is available for this article.

CT/MRI and CEUS LI-RADS Major Features Association with Hepatocellular Carcinoma: Individual Patient Data Meta-Analysis.

Background The Liver Imaging Reporting and Data System (LI-RADS) assigns a risk category for hepatocellular carcinoma (HCC) to imaging observations. Establishing the contributions of major features can inform the diagnostic algorithm. Purpose To perform a systematic review and individual patient data meta-analysis to establish the probability of HCC for each LI-RADS major feature using CT/MRI and contrast-enhanced US (CEUS) LI-RADS in patients at high risk for HCC. Materials and Methods Multiple databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus) were searched for studies from January 2014 to September 2019 that evaluated the accuracy of CT, MRI, and CEUS for HCC detection using LI-RADS (CT/MRI LI-RADS, versions 2014, 2017, and 2018; CEUS LI-RADS, versions 2016 and 2017). Data were centralized. Clustering was addressed at the study and patient levels using mixed models. Adjusted odds ratios (ORs) with 95% CIs were determined for each major feature using multivariable stepwise logistic regression. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) (PROSPERO protocol: CRD42020164486). Results A total of 32 studies were included, with 1170 CT observations, 3341 MRI observations, and 853 CEUS observations. At multivariable analysis of CT/MRI LI-RADS, all major features were associated with HCC, except threshold growth (OR, 1.6; 95% CI: 0.7, 3.6; P = .07). Nonperipheral washout (OR, 13.2; 95% CI: 9.0, 19.2; P = .01) and nonrim arterial phase hyperenhancement (APHE) (OR, 10.3; 95% CI: 6.7, 15.6; P = .01) had stronger associations with HCC than enhancing capsule (OR, 2.4; 95% CI: 1.7, 3.5; P = .03). On CEUS images, APHE (OR, 7.3; 95% CI: 4.6, 11.5; P = .01), late and mild washout (OR, 4.1; 95% CI: 2.6, 6.6; P = .01), and size of at least 20 mm (OR, 1.6; 95% CI: 1.04, 2.5; P = .04) were associated with HCC. Twenty-five studies (78%) had high risk of bias due to reporting ambiguity or study design flaws. Conclusion Most Liver Imaging Reporting and Data System major features had different independent associations with hepatocellular carcinoma; for CT/MRI, arterial phase hyperenhancement and washout had the strongest associations, whereas threshold growth had no association. © RSNA, 2021 Online supplemental material is available for this article.

Diagnostic performance of CT versus MRI Liver Imaging Reporting and Data System category 5 for hepatocellular carcinoma: a systematic review and meta-analysis of comparative studies.

OBJECTIVE: To compare the performance of Liver Imaging Reporting and Data System category 5 (LR-5) for diagnosing HCC between CT and MRI using comparative studies. METHODS: The MEDLINE and EMBASE databases were searched from inception to April 21, 2021, to identify studies that directly compare the diagnostic performance of LR-5 for HCC between CT and MRI. A bivariate random-effects model was fitted to calculate the pooled per-observation sensitivity and specificity of LR-5 of each modality, and compare the pooled estimates of paired data. Subgroup analysis was performed according to the MRI contrast agent. RESULTS: Seven studies with 1145 observations (725 HCCs) were included in the final analysis. The pooled per-observation sensitivity of LR-5 for diagnosing HCC was higher using MRI (61%; 95% confidence interval [CI], 43-76%; I2 = 95%) than CT (48%; 95% CI, 31-65%; I2 = 97%) (p < 0.001). The pooled per-observation specificities of LR-5 did not show statistically significant difference between CT (96%; 95% CI, 92-98%; I2 = 0%) and MRI (93%; 95% CI, 88-96%; I2 = 16%) (p = 0.054). In the subgroup analysis, extracellular contrast agent-enhanced MRI showed significantly higher pooled per-observation sensitivity than gadoxetic acid-enhanced MRI for diagnosing HCC (73% [95% CI, 55-85%] vs. 55% [95% CI, 39-70%]; p = 0.007), without a significant difference in specificity (93% [95% CI, 80-98%] vs. 94% [95% CI, 87-97%]; p = 0.884). CONCLUSIONS: The LR-5 of MRI showed significantly higher pooled per-observation sensitivity than CT for diagnosing HCC. The pooled per-observation specificities of LR-5 were comparable between the two modalities. KEY POINTS: • The pooled sensitivity of LR-5 using MRI was higher than that using CT (61% versus 48%), but the pooled specificities of LR-5 were not significantly different between CT and MRI (96% versus 93%). • Subgroup analysis according to the MRI contrast media showed a significantly higher pooled per-observation sensitivity using ECA-enhanced MRI than with EOB-enhanced MRI (73% versus 55%), and comparable specificities (93% versus 94%). • Although LI-RADS provides a common diagnostic algorithm for CT or MRI, the per-observation performance of LR-5 can be affected by the imaging modality as well as the MRI contrast agent.

Incorporation of Ancillary MRI Features Into the LI-RADS Treatment Response Algorithm: Impact on Diagnostic Performance After Locoregional Treatment of Hepatocellular Carcinoma.

BACKGROUND. The LI-RADS treatment response algorithm may lack sufficient sensitivity for viable tumor after locoregional treatment (LRT) for hepatocellular carcinoma (HCC). OBJECTIVE. The purpose of our study was to evaluate the impact of incorporation of ancillary MRI features on the diagnostic performance of the LI-RADS treatment response algorithm after LRT for HCC. METHODS. This retrospective study included 141 patients (114 men, 27 women; median age, 56 years) who underwent gadoxetic acid-enhanced MRI after LRT for HCC between October 2005 and January 2020 and subsequent liver surgery. Two readers assessed lesions for LI-RADS features of viability for ancillary MRI features (transitional phase [TP] hypointensity, hepatobiliary phase [HBP] hypointensity, DWI hyperintensity or low ADC, and mild-to-moderate T2 hyperintensity). Interobserver agreement was assessed before reaching consensus. Significant ancillary features were identified using random forest analysis. The impact of incorporation of significant ancillary features on diagnostic performance for incomplete pathologic necrosis (IPN; pathologically viable tumor > 0 mm) was assessed using McNemar tests. RESULTS. Complete pathologic necrosis (CPN) was observed in 88 of 181 (48.6%) lesions. Interreader agreement was almost perfect for LI-RADS features of viability (κ = 0.92-0.97) and was substantial to almost perfect for ancillary features (κ = 0.73-0.94). Random forest analysis identified TP hypointensity (present in 8.0%, 25.0%, and 75.3% of lesions with CPN, viable tumor < 10 mm, and viable tumor ≥ 10 mm, respectively) and HBP hypointensity (9.2%, 25.0%, and 74.0%, respectively) as significant ancillary features. For detecting IPN, LR-TR (treatment response) Viable or LR-TR Equivocal had higher sensitivity than LR-TR Viable (71.0% vs 57.0%, respectively; p = .001) but had lower specificity (86.4% vs 94.3%, p = .02). However, LR-TR Viable or LR-TR Equivocal and TP hypointensity showed higher sensitivity than LR-TR Viable (64.5% vs 57.0%, p = .02) without a significantly different specificity (90.9% vs 94.3%, p = .25). LR-TR Viable or LR-TR Equivocal and HBP hypointensity also showed higher sensitivity than LR-TR Viable (65.6% vs 57.0%, p = .01) without a significantly different specificity (90.8% vs 94.3%, p = .25). CONCLUSION. TP hypointensity and HBP hypointensity increase the sensitivity of LI-RADS treatment response algorithm for viable tumor without lowering specificity. CLINICAL IMPACT. The two identified ancillary features may improve tumor viability assessment and planning of additional therapies after LRT for HCC.

Utility of Diffusion-Weighted MRI for Detection of Locally Recurrent Pancreatic Cancer After Surgical Resection.

BACKGROUND. Overlapping imaging findings between local tumor recurrence and postsurgical fibrosis represent a major clinical challenge after pancreatic ductal adeno-carcinoma (PDAC) resection. OBJECTIVE. The purpose of this study was to compare the diagnostic performance of MRI with and without DWI for differentiating locally recurrent tumor and postsurgical fibrosis after PDAC resection. METHODS. This retrospective study included 66 patients (35 men, 31 women; mean age, 60.5 years) who underwent PDAC resection between January 2009 and March 2016, postoperative surveillance CT showing a soft-tissue lesion at the operative site or at the site of peripancreatic vessels, and subsequent MRI with DWI for further evaluation. CT at least 6 months after MRI served as the reference standard, with increase in size of the soft tissue by 5 mm or more differentiating locally recurrent tumor (n = 26) and postsurgical fibrosis (n = 40). Two observers in consensus evaluated MRI characteristics of the soft-tissue lesions. Two additional observers independently reviewed MRI examinations in two separate sessions (conventional MRI alone vs MRI with DWI), recording likelihood of recurrent tumor using a 1-5 scale. ROC analysis was performed, considering scores of 4 or 5 as positive. RESULTS. Subjective diffusion restriction was more common in locally recurrent tumor than postsurgical fibrosis (88.5% vs 25.0%, p = .01). Median ADC was lower for locally recurrent tumor than postsurgical fibrosis (1.3 vs 1.7 × 10-3 mm2/s, p < .001). For both observers, MRI with DWI in comparison with conventional MRI alone showed higher AUC for diagnosis of locally recurrent tumor (observer 1: 0.805 vs 0.707, p = .048; observer 2: 0.898 vs 0.637, p < .001) and higher sensitivity (observer 1: 88.5% vs 61.5%, p = .008; observer 2: 84.6% vs 42.3%, p = .001) but no difference in specificity (observer 1: 72.5% vs 80.0%, p = .08; observer 2, 95.0% vs 85.0%, p = .10). Interobserver agreement was moderate for conventional MRI (κ = 0.41) and good for conventional MRI with DWI (κ = 0.62). CONCLUSION. The addition of DWI to conventional MRI improves the differentiation of locally recurrent tumor and postsurgical fibrosis after PDAC resection, primarily because of improved sensitivity for recurrence. CLINICAL IMPACT. The findings indicate a potential role for MRI with DWI in surveillance protocols after PDAC resection.

Hyperprogressive disease during PD-1 blockade in patients with advanced hepatocellular carcinoma.

BACKGROUND & AIMS: Programmed cell death-1 (PD-1) inhibitor treatment can cause hyperprogressive disease (HPD), but the incidence, outcome, and predictive factors of HPD are unknown in patients with hepatocellular carcinoma (HCC). Herein, we assessed the existence and factors predictive of HPD in patients with advanced HCC treated with nivolumab. METHODS: We enrolled 189 patients with advanced HCC treated with nivolumab. Occurrence of HPD was investigated using tumour growth dynamics based on tumour growth kinetics (TGK) and tumour growth rate (TGR) before and after treatment, or time to treatment failure. We additionally analysed patients treated with regorafenib (n = 95) or best supportive care (BSC)/placebo (n = 103) after progression on sorafenib to compare tumour growth dynamics. RESULTS: Flare-up of tumour growth was observed in a fraction of patients upon PD-1 blockade, indicating the occurrence of HPD. Based on distinct patterns of disease progression exclusively observed in the nivolumab-treated cohort, but not in the regorafenib- or BSC/placebo-treated cohorts, 4-fold increases in TGK and TGR ratios as well as a 40% increase in TGR were the cut-off values used to define HPD; 12.7% of the patients (24/189) treated with nivolumab met all these criteria. Patients with HPD had worse progression-free survival (hazard ratio [HR] 2.194; 95% CI 1.214-3.964) and overall survival (HR 2.238; 95% CI 1.233-4.062) compared to patients with progressive disease without HPD. More than 90% of patients with HPD missed the opportunity for subsequent treatment because of rapid clinical deterioration. An elevated neutrophil-to-lymphocyte ratio (>4.125) was associated with HPD and an inferior survival rate. CONCLUSIONS: HPD occurs in a fraction of patients with HCC who receive PD-1 inhibitor treatment. Analyses of the baseline immune profile and on-treatment tumour growth dynamics could enable optimal patient selection and earlier identification of HPD. LAY SUMMARY: Hyperprogressive disease is an unexpected response pattern observed in patients treated with an immune checkpoint inhibitor. This study revealed that hyperprogressive disease occurs in a fraction of patients with advanced hepatocellular carcinoma treated with an anti-PD-1 antibody, providing evidence to encourage careful monitoring of patients to prevent clinical deterioration induced by PD-1 blockade.

Comparison of Super-Resolution US and Contrast Material-enhanced US in Detection of the Spoke Wheel Sign in Patients with Focal Nodular Hyperplasia.

Background Diagnosis of focal nodular hyperplasia (FNH) with US generally requires the use of contrast material. The effect of the super-resolution US technique on the diagnosis of FNH is unknown. Purpose To investigate the equivalence between super-resolution US and contrast material-enhanced US in the detection of spoke wheel sign in patients with FNH by comparing patterns of tumor vascularity. Materials and Methods This is a secondary analysis of a prospective trial (NCT02737865) that enrolled participants diagnosed with FNH between May 2016 and March 2019. These patients underwent super-resolution US and subsequent contrast-enhanced US with perfluorobutane microbubbles on the same day. The primary outcome was the confidence score of detecting spoke wheel sign in patients with FNH at US. Two radiologists used a four-point scale to score their confidence in the presence of the spoke wheel sign based on super-resolution US and contrast-enhanced US findings. Two one-sided tests were used to test the equivalence between super-resolution US and contrast-enhanced US in terms of the score for the confidence level of the spoke wheel sign. Interobserver agreement for both techniques between the two radiologists, using the recorded images, was analyzed by using an intraclass correlation coefficient. Results In 62 patients (mean age, 37 years; range, 20-69 years; 41 women) with FNH, the majority of patients showed a spoke wheel sign at super-resolution US and contrast-enhanced US (63% [39 of 62] and 71% [44 of 62], respectively; P = .36). There was no significant difference between the super-resolution US and contrast-enhanced US techniques regarding the confidence score for the spoke wheel sign (mean score, 1.8 vs 2.0; P = .03 for equivalence test). The intraclass correlation coefficients of super-resolution US and contrast-enhanced US regarding the presence of the spoke wheel sign were 0.82 (95% confidence interval: 0.73, 0.96) and 0.58 (95% confidence interval: 0.41, 0.73), respectively. Conclusion In comparison with contrast-enhanced US, super-resolution US provided a reliable rate of detection of the spoke wheel sign in patients with focal nodular hyperplasia. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Fetzer in this issue.

Diagnostic Performance of Liver Imaging Reporting and Data System Version 2017 Versus Version 2018 for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis of Comparative Studies.

BACKGROUND: The Liver Imaging Reporting and Data System (LI-RADS) is a comprehensive system for standardizing liver imaging in patients at risk for hepatocellular carcinoma (HCC). PURPOSE: To systematically compare the performance of computed tomography (CT)/MRI LI-RADS category 5 (LR-5) for diagnosing HCC between versions 2017 and 2018. STUDY TYPE: Systematic review and meta-analysis. SUBJECTS: Six articles with 1181 lesions. FIELD STRENGTH/SEQUENCE: 1.5 T and 3.0 T. ASSESSMENT: Data extraction was independently performed by two reviewers who identified and reviewed articles comparing the performance of LR-5 for diagnosing HCC between CT/MRI LI-RADS versions 2017 and 2018. Study and patient characteristics, index test characteristics, reference standards, and study outcomes were extracted from included studies. Risk of bias and concerns regarding applicability were evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. STATISTICAL TESTS: Bivariate random-effects models were used to calculate the pooled per-observation sensitivity and specificity of LR-5 using both versions. The summary receiver operating characteristic curves were plotted. Meta-regression analysis was performed to explore heterogeneity. A P-value <0.05 was considered to be statistically significant for all analyses other than heterogeneity, where the significance threshold was 0.1. RESULTS: The pooled per-observation sensitivity of LR-5 for diagnosing HCC did not show statistically significant difference between versions 2017 (60%; 95% confidence interval [CI], 49%-70%) and 2018 (67%; 95% CI, 56%-76%; P = 0.381). The pooled per-observation specificities of LR-5 were not significantly different between versions 2017 (92%; 95% CI, 90%-95%) and 2018 (91%; 95% CI, 88%-93%; P = 0.332). Meta-regression analyses revealed that the most common underlying liver disease (hepatitis B or hepatitis C) was a significant factor contributing to the heterogeneity of sensitivities among studies for both versions. DATA CONCLUSION: In this meta-analysis using intraindividual paired comparisons, the pooled sensitivity and pooled specificity of LR-5 were not significantly different between 2017 and 2018 LI-RADS versions. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Prognostic significance of sarcopenia in microsatellite-stable gastric cancer patients treated with programmed death-1 inhibitors.

BACKGROUND: Sarcopenia has been underscored as a significant predictor of poor prognosis in cancer patients undergoing immunotherapy with programmed death-1 (PD-1) inhibitors. We aimed to investigate the prognostic significance of computed tomography (CT)-determined sarcopenia in patients with microsatellite-stable (MSS) gastric cancer (GC) treated with PD-1 inhibitors. METHODS: We retrospectively assessed patients with MSS GC who had been treated with PD-1 inhibitors from March 2016 to June 2019. Pre-treatment sarcopenic status was determined by analyzing L3 skeletal muscle index with abdominal CT. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and the differences in survival probability according to sarcopenic status were compared using the log-rank test. Cox proportional hazards regression analyses were performed to identify predictors of PFS and OS. RESULTS: Of 149 patients with MSS GC (mean age, 57.0 ± 12.3 years; 93 men), 79 (53.0%) had sarcopenia. Patients with sarcopenia had significantly shorter PFS than patients without sarcopenia (median, 1.4 months vs. 2.6 months; P = 0.026). Sarcopenia was independently associated with shorter PFS (adjusted hazard ratio [HR], 1.79; 95% confidence interval [CI], 1.10-2.93; P = 0.020). Patients with sarcopenia had shorter OS than patients without sarcopenia (median, 3.6 months vs. 4.9 months; P = 0.052), but sarcopenia itself was not a significant prognostic factor for OS (adjusted HR, 1.01; 95% CI, 0.58-1.75; P = 0.974). CONCLUSIONS: CT-determined sarcopenia is an independent prognostic factor for PFS in patients with MSS GC treated with PD-1 inhibitors.

MRI Ancillary Features for LI-RADS Category 3 and 4 Observations: Improved Categorization to Indicate the Risk of Hepatic Malignancy.

OBJECTIVE. The purpose of this study was to investigate whether ancillary features can help stratify malignancy risk in Liver Imaging Reporting and Data System (LI-RADS) category 3 (LR-3) and 4 (LR-4) observations. MATERIALS AND METHODS. This retrospective longitudinal study included 106 LR-3 or LR-4 observations on gadolinium-enhanced MRI obtained from January 2014 to December 2015 in 80 patients who were treatment naïve and at risk (mean age, 58.0 ± 10.7 [SD] years; 60 men). The presence of major and ancillary features, the category determined using only major features, and the final category adjusted by the application of ancillary features were retrospectively analyzed. MRI features were compared using generalized estimating equations, and cumulative incidence curves for malignancy were compared using log-rank tests with a resampling extension. RESULTS. At 6-month follow-up, the cumulative incidence of observations initially categorized as LR-4, observations upgraded to LR-4, observations initially categorized as LR-3, and observations downgraded to LR-3 were 62.5%, 29.7%, 6.2%, and 0%, respectively. The cumulative incidence of malignancy did not differ between observations categorized by major feature as LR-3 and LR-4 (p = 0.12), but was higher in final observations categorized as LR-4 than in those categorized as LR-3 (p < 0.001). Among observations categorized by major feature as LR-3, the cumulative incidence of malignancy was higher in observations upgraded to LR-4 than in observations that were initially graded as LR-3 (p = 0.03), which showed differences in the frequency of restricted diffusion and mild-to-moderate T2-weighted hyperintensity (p < 0.001 for both). CONCLUSION. Final categories determined with ancillary features, instead of categories determined by major features only, can help indicate malignancy risk in LR-3 and LR-4 observations on MRI.

Hepatocellular Carcinoma versus Other Hepatic Malignancy in Cirrhosis: Performance of LI-RADS Version 2018.

Purpose To evaluate the diagnostic accuracy of the Liver Imaging Reporting and Data System (LI-RADS) version 2018 for differentiating between hepatocellular carcinoma (HCC) and other (hepatic) malignancy (OM) in patients with liver cirrhosis. Materials and Methods From 2008 to 2017, 55 patients with untreated OM and liver cirrhosis were eligible for this retrospective case-control study (mean age, 58 years ± 10 [standard deviation] [range, 32-79 years], with 45 men [mean age, 58 years ± 11] and 10 women [mean age, 62 years ± 7]). Control subjects consisted of 165 treatment-naive patients with HCC and liver cirrhosis (mean age, 58 years ± 10 [range, 29-80 years], with 134 men [mean age, 58 years ± 9] and 31 women [mean age, 59 years ± 11]). Two radiologists blinded to the final diagnosis independently determined the presence of LR-M features and major HCC features (non-rim arterial phase hyperenhancement, non-peripheral washout, and enhancing capsule). The diagnostic performances of each feature, the LR-M criteria (probably or definitely malignant, but not specific for HCC), and the LR-5 criteria (definitely HCC) were calculated and compared by using the generalized estimating equation method. Results Individual LR-M features had a sensitivity of 9%-71% and a specificity of 83%-97% for the diagnosis of OM. Major features of HCC had a sensitivity of 62%-83% and a specificity of 69%-89% for the diagnosis of HCC. The LR-M criteria had a sensitivity of 89% (95% confidence interval [CI]: 81%, 97%) for diagnosing OM, with a specificity of 48% (95% CI: 40%, 56%). The LR-5 criteria had a sensitivity of 74% (95% CI: 67%, 81%) for diagnosing HCC, with a specificity of 89% (95% CI: 81%, 97%). The accuracy of the LR-5 criteria was higher than that of the LR-M criteria (78% [95% CI: 72%, 83%] vs 58% [95% CI: 52%, 65%], P <. 001). Conclusion The LR-5 criteria as well as the LR-M criteria can effectively distinguish hepatocellular carcinoma from other hepatic malignancy in patients with liver cirrhosis. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Furlan in this issue.

Pitfalls and problems to be solved in the diagnostic CT/MRI Liver Imaging Reporting and Data System (LI-RADS).

The 2017 Core of the computed tomography (CT)/magnetic resonance imaging (MRI) Liver Imaging Reporting and Data System (LI-RADS) provides clear definitions and concise explanations of the CT/MRI diagnostic algorithm. Nevertheless, there remain some practical and controversial issues that radiologists should be aware of when using the system. This article discusses pitfalls and problems which may be encountered when the version 2017 diagnostic algorithm is used for CT and MRI. The pitfalls include challenges in applying major features and assigning the LR-M category, as well as categorisation discrepancy between CT and MRI. The problems include imprecision of category codes, application of ancillary features, and regional practice variations in hepatocellular carcinoma (HCC) diagnosis. Potential solutions are presented along with these pitfalls and problems. KEY POINTS: • Although the diagnostic algorithm provides clear and detailed explanations, major feature evaluation can be subject to pitfalls and differentiation of HCC and non-HCC malignancy remains challenging. • Ancillary features are optional and equally weighted. However, features such as hepatobiliary phase hypointensity and restricted diffusion have greater impact on HCC diagnosis than other ancillary features and may merit greater emphasis or weighting. • LI-RADS was initially developed from a Western paradigm, which may limit its applicability in the East due to regional practice variations. In Eastern Asia, high sensitivity is prioritised over near-perfect specificity for HCC diagnosis in order to detect tumours at early stages.

Diagnostic accuracy of prospective application of the Liver Imaging Reporting and Data System (LI-RADS) in gadoxetate-enhanced MRI.

OBJECTIVES: To evaluate the diagnostic performance of the LI-RADS (v2014) on gadoxetate-enhanced MRI prospectively applied in actual practice. METHODS: We retrospectively reviewed the prospectively written radiology reports of 143 treatment-naïve at-risk patients who underwent gadoxetate-enhanced liver MRI from January to December 2014, and identified 202 hepatic observations categorized using the LI-RADS. The diagnostic performances of LI-RADS categories for hepatocellular carcinoma (HCC) and hepatic malignancy were calculated. RESULTS: Twenty (69.0 %) of 29 LR-4, 73 (97.3 %) of 75 LR-5, and all of five (100 %) LR-5V observations were HCCs. The remaining two (2.7 %) LR-5 observations were combined hepatocellular-cholangiocarcinomas, while 10 (76.9 %) of 13 LR-M observations were HCCs. The sensitivity and specificity of LR-5/5V for HCC were 60.5 % and 97.3 %, respectively. Including LR-M in the diagnostic criteria for HCC increased sensitivity (68.2 %, p = 0.002) but decreased specificity without statistical significance (93.2 %, p = 0.154). LR-5/5V/M yielded sensitivity of 68.9 % and specificity of 100.0 % for hepatic malignancy. CONCLUSIONS: LI-RADS v2014 was successfully applied on gadoxetate-enhanced MRI in clinical practice. LR-5/5V was the most specific diagnostic measure for HCC, but most LR-M observations were HCCs and a considerable portion of non-HCC malignancies were categorized as LR-4 or LR-5. KEY POINTS: • LR-5/5V provided a highly specific diagnosis for HCC. • Half of non-HCC malignancies were categorized as LR-4 or LR-5. • The majority of LR-M observations were finally diagnosed as HCCs. • More sensitive diagnosis of HCC was feasible with LR-5/5V/M on gadoxetate-enhanced MRI. • Observations in either LR-5/5V or LR-M categories were definitely malignant.

Validation of the 2015 American Thyroid Association Management Guidelines for Thyroid Nodules With Benign Cytologic Findings in the Era of the Bethesda System.

OBJECTIVE: The purpose of this study is to investigate follow-up strategies for cytologically benign thyroid nodules according to size and ultrasound (US) pattern according to the 2015 American Thyroid Association (ATA) guidelines in the era of the Bethesda system. MATERIALS AND METHODS: This retrospective study included 1208 patients with 1230 nodules that were cytologically benign at initial fine-needle aspiration performed from June 2012 to December 2014. False-negative rates (FNRs) were calculated by considering nodule size and US pattern according to the 2015 ATA guidelines and were compared between nodules with the high-suspicion US pattern and nodules with the high- or intermediate-suspicion US patterns according to size. RESULTS: Twenty-five of the 1230 nodules (2.0%) were malignant. The FNRs were 5.1% (8/158) for nodules with the high-suspicion US pattern and 1.6% (17/1072) for nodules with other US patterns. With regard to nodule size, the FNRs were 3.2% (9/277) for nodules 3 cm or larger and 5.2% (6/115) for nodules 4 cm or larger. The FNRs of nodules with the high-suspicion pattern were not significantly higher than those of nodules with the high- or intermediate-suspicion patterns among nodules 2 cm or larger (2.5% vs 1.9%; p = 0.208), 3 cm or larger (3.4% vs 2.9%; p = 0.498), and 4 cm or larger (5.4% vs 3.8%; p = 0.353). CONCLUSION: Thyroid nodules with initial benign cytologic findings had a low malignancy rate in the era of the Bethesda system, regardless of US pattern and size. Therefore, any immediate diagnostic intervention may be discouraged in cytologically benign nodules.

Preoperative CT and MRI assessment of the longitudinal tumor extent of extrahepatic bile duct cancer after biliary drainage.

PURPOSE: To examine the diagnostic performance for the longitudinal extent of extrahepatic bile duct (EHD) cancer on computed tomography (CT) after biliary drainage (BD) and investigate the appropriate timing of magnetic resonance imaging (MRI) acquisition. METHODS: This retrospective study included patients who underwent curative-intent surgery for EHD cancer and CT pre- and post-BD between November 2005 and June 2021. The biliary segment-wise longitudinal tumor extent was evaluated according to the 2019 Korean Society of Abdominal Radiology consensus recommendations, with pre-BD CT, post-BD CT, and both pre- and post-BD CT. The performance for tumor detectability was compared using GEEs. When preoperative MRI was performed, patients were divided into two subgroups according to the timing of MRI with respect to BD, and the performance of MRI obtained pre- and post-BD was compared. RESULTS: In 105 patients (mean age: 67 ± 8 years; 74 men and 31 women), the performance for tumor detectability was superior using both CT scans compared with using post-BD CT alone (reader 1: sensitivity, 72.6% vs. 64.6%, P < 0.001; specificity, 96.9% vs. 94.8%, P = 0.063; reader 2: sensitivity, 77.2% vs. 72.9%, P = 0.126; specificity, 97.5% vs. 94.2%, P = 0.003), and it was comparable with using pre-BD CT alone. In biliary segments with a catheter, higher sensitivity and specificity were observed using both CT scans than using post-BD CT (reader 1: sensitivity, 74.4% vs. 67.5%, P = 0.006; specificity, 92.4% vs. 88.0%, P = 0.068; reader 2: sensitivity, 80.5% vs. 74.4%, P = 0.013; specificity, 94.3% vs. 88.0%, P = 0.016). Post-BD MRI (n = 30) exhibited a comparable performance to pre-BD MRI (n = 55) (reader 1: sensitivity, 77.9% vs. 75.0%, P = 0.605; specificity, 97.2% vs. 94.9%, P = 0.256; reader 2: sensitivity, 73.2% vs. 72.6%, P = 0.926; specificity, 98.4% vs. 94.9%, P = 0.068). CONCLUSION: Pre-BD CT provided better diagnostic performance in the preoperative evaluation of EHD cancer. The longitudinal tumor extent could be accurately assessed with post-BD MRI, which was similar to pre-BD MRI. CLINICAL SIGNIFICANCE: The acquisition of pre-BD CT could be beneficial for the preoperative evaluation of EHD cancer when BD is planned. Post-BD MRI would not be significantly affected by BD in terms of the diagnostic performance of the longitudinal tumor extent.

Ultrasonographic findings of metabolic dysfunction-associated fatty liver disease: A comparative study with non-alcoholic fatty liver disease and clinical characteristics.

PURPOSE: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new term proposed to replace non-alcoholic fatty liver disease (NAFLD). We analyzed the ultrasonographic findings of MAFLD and NAFLD. METHODS: We conducted a retrospective cross-sectional study of subjects aged ≥19 years who underwent a health screening examination, including ultrasonography, (n = 17,066). Patients were separated into one of three groups; pure MAFLD (n = 5304), pure NAFLD (n = 579), and both NAFLD & MAFLD (n = 11,183). The outcomes were the degree of fatty liver disease and liver cirrhosis, defined by ultrasonography. In addition, the risk of ultrasonographic cirrhosis was assessed in the MAFLD group based on clinical characteristics. RESULTS: The pure NAFLD group had a lower risk of severe fatty liver disease than the both NAFLD & MAFLD groups (0.9 % vs. 4.4 %, p < 0.001). Cirrhosis was not diagnosed in the NAFLD group. Cirrhosis was more common in the pure MAFLD group than in the both NAFLD & MAFLD group (0.3 % vs. 0.0 %, p < 0.001). In the MAFLD group, multivariable analysis showed that diagnosis by hepatic steatosis index (Odds ratio [OR], 12.39; 95 % confidence interval [CI], 3.40-45.19; p < 0.001) or significant alcohol intake (OR, 9.58, 95 % CI, 1.93-47.61; p = 0.006) was independently associated with risk of liver cirrhosis on ultrasonography. CONCLUSION: Liver cirrhosis was more frequently identified on ultrasonography in patients with MAFLD than in NAFLD. MAFLD diagnosed using the hepatic steatosis index or significant alcohol intake is a risk factor for liver cirrhosis.