LI-RADS CT and MRI Ancillary Feature Association with Hepatocellular Carcinoma and Malignancy: An Individual Participant Data Meta-Analysis.

Background The independent contribution of each Liver Imaging Reporting and Data System (LI-RADS) CT or MRI ancillary feature (AF) has not been established. Purpose To evaluate the association of LI-RADS AFs with hepatocellular carcinoma (HCC) and malignancy while adjusting for LI-RADS major features through an individual participant data (IPD) meta-analysis. Materials and Methods Medline, Embase, Cochrane Central Register of Controlled Trials, and Scopus were searched from January 2014 to January 2022 for studies evaluating the diagnostic accuracy of CT and MRI for HCC using LI-RADS version 2014, 2017, or 2018. Using a one-step approach, IPD across studies were pooled. Adjusted odds ratios (ORs) and 95% CIs were derived from multivariable logistic regression models of each AF combined with major features except threshold growth (excluded because of infrequent reporting). Liver observation clustering was addressed at the study and participant levels through random intercepts. Risk of bias was assessed using a composite reference standard and Quality Assessment of Diagnostic Accuracy Studies 2. Results Twenty studies comprising 3091 observations (2456 adult participants; mean age, 59 years ± 11 [SD]; 1849 [75.3%] men) were included. In total, 89% (eight of nine) of AFs favoring malignancy were associated with malignancy and/or HCC, 80% (four of five) of AFs favoring HCC were associated with HCC, and 57% (four of seven) of AFs favoring benignity were negatively associated with HCC and/or malignancy. Nonenhancing capsule (OR = 3.50 [95% CI: 1.53, 8.01]) had the strongest association with HCC. Diffusion restriction (OR = 14.45 [95% CI: 9.82, 21.27]) and mild-moderate T2 hyperintensity (OR = 10.18 [95% CI: 7.17, 14.44]) had the strongest association with malignancy. The strongest negative associations with HCC were parallels blood pool enhancement (OR = 0.07 [95% CI: 0.01, 0.49]) and marked T2 hyperintensity (OR = 0.18 [95% CI: 0.07, 0.45]). Seventeen studies (85%) had a high risk of bias. Conclusion Most LI-RADS AFs were independently associated with HCC, malignancy, or benignity as intended when adjusting for major features. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Crivellaro in this issue.

Suboptimal performance of LI-RADS v2018 on gadoxetic acid-enhanced MRI for detecting hepatocellular carcinoma in liver transplant candidates.

OBJECTIVES: To evaluate the diagnostic performance for hepatocellular carcinoma (HCC) detection of the Liver Imaging Reporting and Data System (LI-RADS) version 2018 on gadoxetic acid-enhanced MRI, comparing liver transplant candidates (LT group) with patients who underwent surgical resection (SR group), and to determine significant clinical factors for diagnostic performance of LI-RADS v2018. METHODS: Patients who underwent gadoxetic acid-enhanced MRI and subsequent SR or LT for HCC were retrospectively included between January 2019 and December 2020. The sensitivity and specificity of LI-RADS LR-5 for HCC were compared between the two groups using generalized estimating equations. The accuracy of patient allocation according to the Milan criteria was calculated for the LT group. Univariable and multivariable logistic regression analyses were performed to determine significant clinical factors associated with the sensitivity of LI-RADS. RESULTS: Of the 281 patients, 237 were assigned to the SR group, and 44 were assigned to the LT group. The LT group showed significantly lower per-patient (48.5% vs. 79.6%, p < .001) and per-lesion sensitivity (31.0% vs. 75.9%, p < .001) than the SR group, whereas no significant difference in both per-patient (100.0% vs. 91.7%, p > .99) and per-lesion specificities (100.0% vs. 94.1%, p > .99). The accuracy of patient allocation was 50.0%. Sensitivity was significantly lower in patients with a smaller lesion size (p < .001), a larger lesion number (p = .002), and a higher Child-Pugh score (p = .009). CONCLUSION: LI-RADS v2018 on gadoxetic acid-enhanced MRI might be insufficient in liver transplant candidates and other diagnostic imaging tests should be considered in patients with these significant clinical factors. CLINICAL RELEVANCE STATEMENT: In liver transplant candidates with a smaller lesion size, a larger lesion number, and a higher Child-Pugh score, imaging tests other than gadoxetic acid-enhanced MRI may be clinically useful to determine the transplant eligibility. KEY POINTS: • The sensitivity of the Liver Imaging Reporting and Data System (LI-RADS) was lower in liver transplant candidates than in those who underwent surgical resection. • With the use of gadoxetic acid-enhanced MRI, the accuracy of patient allocation for liver transplantation on the basis of the Milan criteria was suboptimal. • The sensitivity of LI-RADS v2018 was significantly associated with lesion size, lesion number, and Child-Pugh classification.

LI-RADS threshold growth based on tumor growth rate can improve the diagnosis of hepatocellular carcinoma ≤ 3.0 cm.

OBJECTIVE: Despite the revision of threshold growth (TG) in the Liver Imaging Reporting and Data System (LI-RADS) version 2018, the appropriate time period between the two examinations for TG has not been determined. We compared the accuracy of LI-RADS with TG based on tumor growth rate for the diagnosis of hepatocellular carcinoma (HCC) with that of LI-RADS v2018 based on the original TG. METHODS: Patients who underwent preoperative MRI for focal solid lesions (≤ 3.0 cm) were retrospectively evaluated. Three readers measured the size of each lesion on prior CT/MRI and index MRI, with tumor growth rate defined as the percent change in lesion size per month. In addition to the original TG (≥ 50% size increase within ≤ 6 months), the modified TG based on tumor growth rates ≥ 10%/month (TG-10%), ≥ 20%/month (TG-20%), and ≥ 30%/month (TG-30%) were evaluated. The accuracies of these evaluation methods for LI-RADS category 5 HCC were compared using generalized estimation equations. RESULTS: A total of 508 lesions from 370 patients were evaluated. Compared with LI-RADS v2018 with the original TG, the accuracy of LI-RADS with TG-10% was significantly higher (85.0% vs. 80.7%, p < .001), whereas the accuracies of LI-RADS with TG-20% (81.3% vs. 80.7%, p = .404) and TG-30% (79.3% vs. 80.7%, p = .052) were not significant. The sensitivity of LI-RADS with TG-10% was higher than that of LI-RADS v2018 (79.0% vs. 72.5%, p < .001), whereas their specificities were not significantly different (96.6% vs. 96.6%, p > .999). CONCLUSION: TG-10% improved the sensitivity of LI-RADS by detecting additional hepatocellular carcinomas underestimated due to short-term follow-up. CLINICAL RELEVANCE STATEMENT: Threshold growth based on tumor growth rate can be clinically useful in the diagnosis of hepatocellular carcinoma, by improving the sensitivity of LI-RADS. KEY POINTS: • The diagnostic accuracy of Liver Imaging Reporting and Data System (LI-RADS) v2018 was not significantly affected by the time interval between prior and index assessments of threshold growth. • In the 334 hepatocellular carcinomas, the frequency of threshold growth was significantly higher using tumor growth rate ≥ 10%/month (TG-10%) than original threshold growth (53.3% vs. 18.0%, p < .001). • Compared with LI-RADS v2018 with the original threshold growth, LI-RADS with TG-10% had significantly higher accuracy (85.0% vs. 80.7%, p < .001) and sensitivity (79.0% vs. 72.5%, p < .001) but a similar specificity (96.6% vs. 96.6%, p > .999).

Cytarabine induces cachexia with lipid malabsorption via zippering the junctions of lacteal in murine small intestine.

Chemotherapy-induced cachexia causes severe metabolic abnormalities independently of cancer and reduces the therapeutic efficacy of chemotherapy. The underlying mechanism of chemotherapy-induced cachexia remains unclear. Here we investigated the cytarabine (CYT)-induced alteration in energy balance and its underlying mechanisms in mice. We compared energy balance-associated parameters among the three groups of mice: CON, CYT, and PF (pair-fed mice with the CYT group) that were intravenously administered vehicle or CYT. Weight gain, fat mass, skeletal muscle mass, grip strength, and nocturnal energy expenditure were significantly lowered in the CYT group than in the CON and PF groups. The CYT group demonstrated less energy intake than the CON group and higher respiratory quotient than the PF group, indicating that CYT induced cachexia independently from the anorexia-induced weight loss. Serum triglyceride was significantly lower in the CYT group than in the CON group, whereas the intestinal mucosal triglyceride levels and the lipid content within the small intestine enterocyte were higher after lipid loading in the CYT group than in the CON and PF groups, suggesting that CYT inhibited lipid uptake in the intestine. This was not associated with obvious intestinal damage. The CYT group showed increased zipper-like junctions of lymphatic endothelial vessel in duodenal villi compared to that in the CON and CYT groups, suggesting their imperative role in the CYT-induced inhibition of lipid uptake. CYT worsens cachexia independently of anorexia by inhibiting the intestinal lipid uptake, via the increased zipper-like junctions of lymphatic endothelial vessel.

Value of threshold growth as a major diagnostic feature of hepatocellular carcinoma in LI-RADS.

BACKGROUND & AIMS: The Liver Reporting and Data System (LI-RADS) version 2018 simplified the definition of threshold growth to '≥50% size increase in a mass in ≤6 months'. However, the diagnostic value of threshold growth for hepatocellular carcinoma (HCC) remained unclear. We evaluated the value of threshold growth, as defined by LI-RADS v2018, in diagnosing HCCs. METHODS: Patients who underwent preoperative gadoxetate disodium-enhanced MRI because of the presence of LI-RADS category 2, 3, or 4 rather than category 5 on prior CT/MRI between January 2017 and December 2020 were retrospectively evaluated. Pathologic or clinical diagnoses were used as reference standards. Imaging features were evaluated by three readers according to LI-RADS v2018. The frequency and diagnostic odds ratio of threshold growth were calculated. The diagnostic performance of LI-RADS category 5 was separately evaluated when threshold growth was and was not considered a major feature, and results were compared using generalized estimation equations. Subgroups of patients who underwent CT/MRI during the previous 3-6 months were analyzed. RESULTS: Analysis of 340 observations in 243 patients found that the frequency of threshold growth was 18.8% and it gradually increased over time. Threshold growth was significantly associated with HCC (diagnostic odds ratio 5.2; 95% CI 2.1-12.7; p <0.001). Use of threshold growth as a major feature significantly increased sensitivity in both the overall (66.4% vs. 57.3%, p <0.001) and subgroup (73.4% vs. 58.2%, p <0.001) cohorts, but had no effect on specificity in either the overall (97.5% vs. 98.3%, p = 0.319) or subgroup (95.9% vs. 98.0%, p = 0.323) cohorts. CONCLUSION: The revised threshold growth of LI-RADS v2018 was significantly associated with HCC. Use of threshold growth as a major diagnostic feature of HCC can improve the sensitivity of LI-RADS v2018. IMPACT AND IMPLICATIONS: We found that the revised threshold growth in the Liver Imaging Reporting and Data System version 2018 (LI-RADS v2018) was a significant predictor of hepatocellular carcinoma (HCC). The use of threshold growth as a major imaging feature of HCC significantly increased the sensitivity of LI-RADS v2018, especially small HCCs (≤3.0 cm), compared with its non-use. Because these small HCCs are eligible for curative treatments, the additional detection of small HCCs is clinically meaningful.

CT Rule-in and Rule-out Criteria for Clinically Significant Portal Hypertension in Chronic Liver Disease.

Background The value of CT in assessment of clinically significant portal hypertension (CSPH) has not been well determined. Purpose To evaluate the performance of CT features that have been associated with portal hypertension for diagnosing CSPH in patients with chronic liver disease (CLD). Materials and Methods This retrospective study included patients with CLD who underwent contrast-enhanced CT and subsequent hepatic venous pressure gradient (HVPG) measurement within 3 months at two tertiary institutions from January 2001 to December 2019. Two readers independently evaluated the presence of gastroesophageal varix, spontaneous portosystemic shunt (SPSS), and ascites on CT images. Splenomegaly at CT was determined using three methods, as follows: personalized or fixed volume criteria, based on spleen volume as measured by a deep learning algorithm, or manually measured spleen diameter. The diagnostic performance of these findings alone or in combination for detecting CSPH (HVPG ≥10 mm Hg) was evaluated. Results A total of 235 patients (mean age, 53.2 years ± 13.0 [SD]; 155 male patients), including 110 (46.8%) with CSPH, were included. Detection of CSPH according to the presence of both splenomegaly and at least one other CT feature (ie, gastroesophageal varix, SPSS, and ascites) achieved specificities of 94.4%-97.6%, whereas detection of CSPH according to the presence of any feature (ie, splenomegaly, gastroesophageal varix, SPSS, or ascites) achieved sensitivities of 94.5%-98.2%. When employing the former as rule-in criteria with the absence of splenomegaly, gastroesophageal varix, SPSS, and ascites as rule-out criteria for CSPH, 171-185 (range, 72.8%-78.7%) of 235 patients were correctly classified as either having CSPH or not, seven to 13 (range, 3%-5.5%) of 235 patients were incorrectly classified, and 42-54 (range, 17.9%-23%) of 235 patients were unclassified. Conclusion The presence or absence of splenomegaly, gastroesophageal varix, SPSS, and/or ascites on CT images may be useful for ruling in and ruling out CSPH in patients with CLD. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Fraum in this issue.

Individual Participant Data Meta-Analysis of LR-5 in LI-RADS Version 2018 versus Revised LI-RADS for Hepatocellular Carcinoma Diagnosis.

Background A simplification of the Liver Imaging Reporting and Data System (LI-RADS) version 2018 (v2018), revised LI-RADS (rLI-RADS), has been proposed for imaging-based diagnosis of hepatocellular carcinoma (HCC). Single-site data suggest that rLI-RADS category 5 (rLR-5) improves sensitivity while maintaining positive predictive value (PPV) of the LI-RADS v2018 category 5 (LR-5), which indicates definite HCC. Purpose To compare the diagnostic performance of LI-RADS v2018 and rLI-RADS in a multicenter data set of patients at risk for HCC by performing an individual patient data meta-analysis. Materials and Methods Multiple databases were searched for studies published from January 2014 to January 2022 that evaluated the diagnostic performance of any version of LI-RADS at CT or MRI for diagnosing HCC. An individual patient data meta-analysis method was applied to observations from the identified studies. Quality Assessment of Diagnostic Accuracy Studies version 2 was applied to determine study risk of bias. Observations were categorized according to major features and either LI-RADS v2018 or rLI-RADS assignments. Diagnostic accuracies of category 5 for each system were calculated using generalized linear mixed models and compared using the likelihood ratio test for sensitivity and the Wald test for PPV. Results Twenty-four studies, including 3840 patients and 4727 observations, were analyzed. The median observation size was 19 mm (IQR, 11-30 mm). rLR-5 showed higher sensitivity compared with LR-5 (70.6% [95% CI: 60.7, 78.9] vs 61.3% [95% CI: 45.9, 74.7]; P < .001), with similar PPV (90.7% vs 92.3%; P = .55). In studies with low risk of bias (n = 4; 1031 observations), rLR-5 also achieved a higher sensitivity than LR-5 (72.3% [95% CI: 63.9, 80.1] vs 66.9% [95% CI: 58.2, 74.5]; P = .02), with similar PPV (83.1% vs 88.7%; P = .47). Conclusion rLR-5 achieved a higher sensitivity for identifying HCC than LR-5 while maintaining a comparable PPV at 90% or more, matching the results presented in the original rLI-RADS study. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Sirlin and Chernyak in this issue.

Visualization Score of Gadoxetic Acid-Enhanced Magnetic Resonance Imaging: The Effect on the Diagnostic Accuracy for Hepatocellular Carcinoma.

BACKGROUND: The visualization score of hepatobiliary-phase (HBP) images has been introduced as an image quality index for gadoxetic acid-enhanced MRI. It may be associated with hepatic function and could have an implication on the diagnostic accuracy for hepatocellular carcinoma (HCC). PURPOSE: To investigate the association between the visualization score of gadoxetic acid-enhanced MRI and clinical factors and to evaluate its effect on the diagnostic accuracy for HCC ≤ 3.0 cm. STUDY TYPE: Retrospective. POPULATION: A total of 493 focal lesions from 397 patients. FIELD STRENGTH/SEQUENCE: A 5-T or 3.0 -T with pre/postcontrast T1-weighted 3D gradient echo sequence, and T2-weighted fast spin-echo sequence ASSESSMENT: Child-Pugh classification and albumin-bilirubin (ALBI) score were assessed. Three readers evaluated the visualization score of each MRI examination (A, no or minimal; B, moderate; and C, severe limitations), and major features (arterial-phase hyperenhancement, washout, enhancing capsule, threshold growth) and ancillary features of each focal lesion. STATISTICAL TESTS: Univariable and multivariable logistic regression analyses were performed to determine significant clinical factors associated with a suboptimal visualization score (B or C). Generalized estimating equations were used to compare the sensitivity and specificity for diagnosing HCC between the two group (visualization score A vs. B or C). A P value < 0.05 was considered statistically significant. RESULTS: Of the 397 MRI examinations, the incidence of suboptimal visualization score was 13%. A suboptimal visualization score was significantly associated with Child-Pugh classification B or C (adjusted odds ratio [OR] = 15.2) and ALBI grade 2 or 3 (OR = 4.7). Compared with the visualization score A group, the suboptimal visualization score group showed significantly lower sensitivity (56.8% vs. 75.2%) and less frequent washout in HCC (62.2% vs. 84.0%). DATA CONCLUSION: The visualization score on gadoxetic acid-enhanced MRI can be an important image quality index and the diagnostic accuracy for HCC ≤ 3.0 cm may not be sufficient in the suboptimal visualization score group. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 3.

Comparative Performance of 2018 LI-RADS versus Modified LIRADS (mLI-RADS): An Individual Participant Data Meta-Analysis.

BACKGROUND: LI-RADS version 2018 (v2018) is used for non-invasive diagnosis of hepatocellular carcinoma (HCC). A recently proposed modification (known as mLI-RADS) demonstrated improved sensitivity while maintaining specificity and positive predictive value (PPV) of LI-RADS category 5 (definite HCC) for HCC. However, mLI-RADS requires multicenter validation. PURPOSE: To evaluate the performance of v2018 and mLI-RADS for liver lesions in a large, heterogeneous, multi-national cohort of patients at risk for HCC. STUDY TYPE: Systematic review and meta-analysis using individual participant data (IPD) [Study Protocol: https://osf.io/duys4]. POPULATION: 2223 observations from 1817 patients (includes all LI-RADS categories; females = 448, males = 1361, not reported = 8) at elevated risk for developing HCC (based on LI-RADS population criteria) from 12 retrospective studies. FIELD STRENGTH/SEQUENCE: 1.5T and 3T; complete liver MRI with gadoxetate disodium, including axial T2w images and dynamic axial fat-suppressed T1w images precontrast and in the arterial, portal venous, transitional, and hepatobiliary phases. Diffusion-weighted imaging was used when available. ASSESSMENT: Liver observations were categorized using v2018 and mLI-RADS. The diagnostic performance of each system's category 5 (LR-5 and mLR-5) for HCC were compared. STATISTICAL TESTS: The Quality Assessment of Diagnostic Accuracy Studies version 2 (QUADAS-2 was applied to determine risk of bias and applicability. Diagnostic performances were assessed using the likelihood ratio test for sensitivity and specificity and the Wald test for PPV. The significance level was P < 0.05. RESULTS: 17% (2/12) of the studies were considered low risk of bias (244 liver observations; 164 patients). When compared to v2018, mLR-5 demonstrated higher sensitivity (61.3% vs. 46.5%, P < 0.001), similar PPV (85.3% vs. 86.3%, P = 0.89), and similar specificity (85.8% vs. 90.8%, P = 0.16) for HCC. DATA CONCLUSION: This study confirms mLR-5 has higher sensitivity than LR-5 for HCC identification, while maintaining similar PPV and specificity, validating the mLI-RADS proposal in a heterogeneous, international cohort. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Multiple arterial-phase MRI with gadoxetic acid improves diagnosis of hepatocellular carcinoma ≤3.0 cm.

BACKGROUND AND AIMS: Multiple arterial-phase magnetic resonance imaging (MA-MRI) was introduced to overcome the limitations of gadoxetic acid-enhanced MRI, but its clinical impacts on hepatocellular carcinoma (HCC) diagnosis have not been well assessed. We investigated whether MA-MRI with gadoxetic acid could improve the diagnosis of HCC ≤3.0 cm in comparison with single arterial-phase MRI (SA-MRI). METHODS: This retrospective study included 397 patients from two tertiary institutions who underwent gadoxetic acid-enhanced MRI (243 patients with 271 lesions in cohort-1 underwent SA-MRI, and 154 patients with 166 lesions in cohort-2 underwent MA-MRI). The patients had 437 hepatic lesions ≤3.0 cm with pathologic confirmation. The arterial-phase image quality and diagnostic performance of SA-MRI and MA-MRI were analysed and compared. To minimize the effects of selection bias because of potential confounding between the two groups, propensity score-matching was additionally performed. RESULTS: MA-MRI showed a significantly higher percentage of optimal arterial-phase timing (94.2% vs. 74.5%, p < .001) and lower incidence of inadequate examinations (1.3% vs. 5.8%, p = .034) than SA-MRI. MA-MRI had a significantly higher non-rim arterial-phase hyperenhancement (APHE) detection rate (94.9% vs. 85.5%, p = .005) and sensitivity for diagnosing HCC (87.4% vs. 70.0%, p < .001) than SA-MRI, but no significant difference in specificity (92.9% vs. 93.1%, p = .966). In 123 pairs of propensity score-matched patients, MA-MRI had significantly higher sensitivity (89.1% vs. 74.5%, p = .006) than SA-MRI with equal specificity (92.3% vs. 92.3%, p > .999). CONCLUSIONS: Compared with SA-MRI, MA-MRI with gadoxetic acid can detect more non-rim APHE and significantly improve sensitivity for diagnosing HCC ≤3.0 cm, without a significant decrease in specificity.

LI-RADS version 2018 for hepatocellular carcinoma < 1.0 cm on gadoxetate disodium-enhanced magnetic resonance imaging.

OBJECTIVES: We aimed to develop and evaluate a modified Liver Imaging Reporting and Data System (LI-RADS) version 2018 using significant ancillary features for diagnosing hepatocellular carcinoma (HCC) < 1.0 cm on gadoxetate disodium-enhanced magnetic resonance imaging (MRI). METHODS: Patients who underwent preoperative gadoxetate disodium-enhanced MRI for focal solid nodules < 2.0 cm within 1 month of MRI between January 2016 and December 2020 were retrospectively analyzed. Major and ancillary features were compared between HCCs of < 1.0 cm and 1.0-1.9 cm using the chi-square test. Significant ancillary features associated with HCC < 1.0 cm were determined by univariable and multivariable logistic regression analysis. The sensitivity and specificity of LR-5 were compared between LI-RADS v2018 and our modified LI-RADS (applying the significant ancillary feature) using generalized estimating equations. RESULTS: Of 796 included nodules, 248 were < 1.0 cm and 548 were 1.0-1.9 cm. HCC < 1.0 cm less frequently showed an enhancing capsule (7.1% vs. 31.1%, p < .001) and threshold growth (0% vs. 8.3%, p = .007) than HCC of 1.0-1.9 cm. Restricted diffusion was the only ancillary feature significant for diagnosing HCC < 1.0 cm (adjusted odds ratio = 11.50, p < .001). In the diagnosis of HCC, our modified LI-RADS using restricted diffusion had significantly higher sensitivity than LI-RADS v2018 (61.8% vs. 53.5%, p < .001), with similar specificity (97.3% vs. 97.8%, p = .157). CONCLUSION: Restricted diffusion was the only significant independent ancillary feature for diagnosing HCC < 1.0 cm. Our modified LI-RADS using restricted diffusion can improve the sensitivity for HCC < 1.0 cm. KEY POINTS: • The imaging features of hepatocellular carcinoma (HCC) < 1.0 cm differed from those of HCC of 1.0-1.9 cm. • Restricted diffusion was the only significant independent ancillary feature for HCC < 1.0 cm. • Modified Liver Imaging Reporting and Data System (LI-RADS) with the addition of restricted diffusion can improve the sensitivity for HCC < 1.0 cm.

Proliferative hepatocellular carcinomas in cirrhosis: patient outcomes of LI-RADS category 4/5 and category M.

OBJECTIVES: We aimed to compare Liver Imaging Reporting and Data System (LI-RADS) category 4/5 and category M (LR-M) of proliferative hepatocellular carcinomas (HCCs) in cirrhotic patients and evaluate their impacts on prognosis. METHODS: This retrospective multi-reader study included cirrhotic patients with single treatment-naïve HCC ≤ 5.0 cm who underwent contrast-enhanced CT, MRI, and subsequent hepatic resection within 2 months. The percentages of CT/MRI LR-4/5 and LR-M in proliferative and non-proliferative HCCs were compared. Univariable and multivariable Cox proportional hazards regression analyses were performed to assess the association of LI-RADS categories (LR-4/5 vs. LR-M) and pathologic classification (proliferative vs. non-proliferative) with overall survival (OS) and recurrence-free survival (RFS). Subgroups of patients with proliferative and non-proliferative HCCs were analyzed to compare OS and RFS between LR-4/5 and LR-M. RESULTS: Of the 204 included patients, 38 were classified as having proliferative HCC. The percentages of LR-M were higher in proliferative than non-proliferative HCC on both CT (15.8% vs. 3.0%, p = 0.007) and MRI (26.3% vs. 9.6%, p = 0.016). Independent of pathologic classification, CT and MRI LR-M were significantly associated with poorer OS (hazard ratio (HR) = 4.58, p = 0.013, and HR = 6.45, p < 0.001) and RFS (HR = 3.66, p = 0.005, and HR = 6.44, p < 0.001) than LR-4/5. MRI LR-M was associated with significantly poorer OS (p ≤ 0.003) and RFS (p < 0.001) than MRI LR-4/5 in both proliferative and non-proliferative HCCs. CONCLUSIONS: This multi-reader study showed that the percentages of LR-M were significantly higher in proliferative than non-proliferative HCCs. CT/MRI LR-M was significantly associated with poor OS and RFS, independent of the pathologic classification of proliferative versus non-proliferative HCCs. CLINICAL RELEVANCE STATEMENT: CT and MRI LI-RADS category M can be clinically useful in predicting poor outcomes in patients with proliferative and non-proliferative hepatocellular carcinomas. KEY POINTS: • The percentages of LR-M tumors on both CT and MRI were significantly higher in proliferative than non-proliferative hepatocellular carcinomas. • Independent of pathologic classification, CT/MRI LR-M categories were correlated with poor overall survival and recurrence-free survival. • Patients with both proliferative and non-proliferative hepatocellular carcinomas categorized as MRI LR-M had significantly poorer overall survival and recurrence-free survival than those categorized as MRI LR-4/5.

Prognostic value of tumor-to-parenchymal contrast enhancement ratio on portal venous-phase CT in pancreatic neuroendocrine neoplasms.

OBJECTIVES: We aimed to evaluate the prognostic value of tumor-to-parenchymal contrast enhancement ratio on portal venous-phase CT (CER on PVP) and compare its prognostic performance to prevailing grading and staging systems in pancreatic neuroendocrine neoplasms (PanNENs). METHODS: In this retrospective study, data on 465 patients (development cohort) who underwent upfront curative-intent resection for PanNEN were used to assess the performance of CER on PVP and tumor size measured by CT (CT-Size) in predicting recurrence-free survival (RFS) using Harrell's C-index and to determine their optimal cutoffs to stratify RFS using a multi-way partitioning algorithm. External data on 184 patients (test cohort) were used to validate the performance of CER on PVP in predicting RFS and overall survival (OS) and compare its predictive performance with those of CT-Size, 2019 World Health Organization classification system (WHO), and the 8th American Joint Committee on Cancer staging system (AJCC). RESULTS: In the test cohort, CER on PVP showed C-indexes of 0.83 (95% confidence interval [CI], 0.74-0.91) and 0.84 (95% CI, 0.73-0.95) for predicting RFS and OS, respectively, which were higher than those for the WHO (C-index: 0.73 for RFS [p = .002] and 0.72 for OS [p = .004]) and AJCC (C-index, 0.67 for RFS [p = .002] and 0.58 for OS [p = .002]). CT-Size obtained C-indexes of 0.71 for RFS and 0.61 for OS. CONCLUSIONS: CER on PVP showed superior predictive performance on postoperative survival in PanNEN than current grading and staging systems, indicating its potential as a noninvasive preoperative prognostic tool. KEY POINTS: • In pancreatic neuroendocrine neoplasms, the tumor-to-parenchymal enhancement ratio on portal venous-phase CT (CER on PVP) showed acceptable predictive performance of postoperative outcomes. • CER on PVP showed superior predictive performance of postoperative survival over the current WHO classification and AJCC staging system.

A model for predicting poor survival in patients with cirrhosis undergoing portosystemic shunt embolization.

BACKGROUND AND AIM: Portosystemic shunt embolization (PSSE) is a promising treatment for hepatic encephalopathy (HEP) and gastric varix (GV) in cirrhotic patients with a spontaneous portosystemic shunt. However, PSSE may worsen portal hypertension causing hepatorenal syndrome, liver failure, and mortality. This study aimed to develop and validate a prognostic model that helps identify patients with a risk of poor short-term survival after PSSE. METHODS: We included 188 patients who underwent PSSE for recurrent HEP or GV at a tertiary center in Korea. To develop a prediction model for 6-month survival after PSSE, Cox proportional-hazard model was used. The developed model was validated in a separate cohort of 184 patients from two other tertiary centers. RESULTS: In multivariable analysis, the 1-year overall survival after PSSE was significantly associated with baseline levels of serum albumin, total bilirubin, and international normalized ratio (INR). We therefore developed the albumin-bilirubin-INR (ABI) score by assigning 1 point each for albumin < 3.0 g/dL, total bilirubin ≥ 1.5 mg/dL, and INR ≥ 1.5. Time-dependent areas under the curve of the ABI score for predicting 3-month and 6-month survival were 0.85 and 0.85 in the development cohort and 0.83 and 0.78 in the validation cohort, indicating good discrimination performance. The ABI score showed a better discrimination and calibration performance than the model for end-stage liver disease and the Child-Pugh scores, especially in high-risk patients. CONCLUSIONS: The ABI score is a simple prognostic model that helps decide whether to proceed with PSSE for the prevention of HEP or GV bleeding in patients with spontaneous portosystemic shunt.

Individual variations lead to universal and cross-species patterns of social behavior.

The duration of interaction events in a society is a fundamental measure of its collective nature and potentially reflects variability in individual behavior. Here we performed a high-throughput measurement of trophallaxis and face-to-face event durations experienced by a colony of honeybees over their entire lifetimes. The interaction time distribution is heavy-tailed, as previously reported for human face-to-face interactions. We developed a theory of pair interactions that takes into account individual variability and predicts the scaling behavior for both bee and extant human datasets. The individual variability of worker honeybees was nonzero but less than that of humans, possibly reflecting their greater genetic relatedness. Our work shows how individual differences can lead to universal patterns of behavior that transcend species and specific mechanisms for social interactions.

Simplified LI-RADS for Hepatocellular Carcinoma Diagnosis at Gadoxetic Acid-enhanced MRI.

Background Although various modifications to the Liver Imaging Reporting and Data System (LI-RADS) at gadoxetic acid-enhanced MRI have been suggested, LI-RADS shows suboptimal sensitivity for hepatocellular carcinoma (HCC) and is perceived to be too complex. Purpose To evaluate clinical usefulness of a simplified LI-RADS for diagnosing HCCs of 30 mm or smaller at gadoxetic acid-enhanced MRI. Materials and Methods Patients who underwent gadoxetic acid-enhanced MRI examination and subsequent resection, transplantation, or biopsy for focal solid nodules of 30 mm or smaller between January 2019 and December 2020 at a single tertiary referral institution were retrospectively analyzed. Two strategies for simplified LI-RADS using one size criterion (≥10 mm) were evaluated (strategy A, using classifications for nodules of 10-19 mm for nodules both 10-19 mm and ≥20 mm; strategy B, using classifications for nodules ≥20 mm for nodules both 10-19 mm and ≥20 mm). Multivariable analysis was performed to determine significant ancillary features for HCC. Generalized estimating equations were used to compare diagnostic performance for LR-5 (definite HCC) between LI-RADS version 2018 and simplified LI-RADS. The time required for LI-RADS category assignment was compared between the two systems with use of a paired t test. Results A total of 645 nodules from 510 patients (mean age ± SD, 60 years ± 10; 393 men) were evaluated. Compared with strategy A, strategy B had a higher sensitivity of 74% (347 of 470 nodules [95% CI: 70, 78]) vs 73% (342 of 470 nodules [95% CI: 69, 77]) (P = .02) with the same specificity of 96% (168 of 175 nodules [95% CI: 92, 98]) vs 96% (168 of 175 nodules [95% CI: 92, 98]) (P > .99). In strategy B, transitional phase hypointensity was an independent ancillary feature for HCC (P = .04) in LR-4 of at least 10 mm with arterial phase hyperenhancement and no other major features. In all 645 nodules, simplified LI-RADS with use of both strategy B and transitional phase hypointensity had a higher sensitivity of 82% (387 of 470 nodules [95% CI: 79, 86]) vs 73% (343 of 470 nodules [95% CI: 69, 77]) (P < .001) than LI-RADS version 2018, without lower specificity (94%, 165 of 175 nodules [95% CI: 90, 97] vs 96%, 168 of 175 nodules [95% CI: 92, 98], P = .08). Compared with LI-RADS version 2018, simplified LI-RADS reduced the time for LI-RADS category assignment (44 seconds ± 23 vs 74 seconds ± 22, P < .001). Conclusion A simplified Liver Imaging Reporting and Data System was found to be clinically useful for diagnosing hepatocellular carcinomas of 30 mm or smaller at gadoxetic acid-enhanced MRI. © RSNA, 2022 Online supplemental material is available for this article.

Noncirrhotic Portal Hypertension after Trastuzumab Emtansine in HER2-positive Breast Cancer as Determined by Deep Learning-measured Spleen Volume at CT.

Background Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate approved for use in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Case reports have suggested an association between T-DM1 and portal hypertension. Purpose To evaluate the association of T-DM1 therapy with spleen volume changes and portal hypertension on CT scans and clinical findings compared with lapatinib and capecitabine therapy. Materials and Methods Patients with HER2-positive breast cancer who were administered at least two cycles of T-DM1 or lapatinib and capecitabine (controls) in a tertiary institution from 2001 to 2020 and who underwent CT before initial treatment and at least once during treatment were retrospectively enrolled. Spleen volume changes and the signs of portal hypertension (gastroesophageal varix [GEV], spontaneous portosystemic shunt [SPSS], and ascites) were evaluated at contrast-enhanced CT. Patients were followed until treatment ended or for 2 years after the start of treatment. Spleen volume changes were measured with a deep learning algorithm and evaluated by using a linear mixed model. The incidences of splenomegaly and portal hypertension were compared between the T-DM1 and control groups by using a χ2 test or Fisher exact test. Results The T-DM1 group included 111 patients (mean age, 54 years ± 11 [SD]; 111 women) and the control group included 122 patients (mean age, 50 years ± 9; 121 women). Spleen volume progressively increased with T-DM1 therapy but was constant in the control group (104% ± 5 vs -1% ± 6 at the 33rd treatment cycle, respectively; P < .001). Incidences of splenomegaly (46% [51 of 111] vs 3% [four of 122] of patients; P < .001), GEV (11% [12 of 111] vs 1% [one of 122] of patients; P < .001), and SPSS (27% [30 of 111] vs 1% [one of 122] of patients; P < .001) were higher in the T-DM1 group than in the control group. Conclusion Trastuzumab emtansine therapy was associated with noncirrhotic portal hypertension at CT, with higher incidences of splenomegaly, gastroesophageal varix, and spontaneous portosystemic shunt than those with lapatinib and capecitabine therapy. © RSNA, 2022 Online 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.

Liver Imaging Reporting and Data System categories: Long-term imaging outcomes in a prospective surveillance cohort.

BACKGROUND AND AIMS: We assessed the imaging outcomes of Liver Imaging Reporting and Data System (LI-RADS) v2018 categories in prospective hepatocellular carcinoma (HCC) surveillance cohort and determined imaging features significantly predictive of progression to a malignant LI-RADS category. METHODS: The imaging outcomes of 120 patients (162 observations) prospectively enrolled between November 2011 and August 2012 were analysed according to LI-RADS v2018. Cumulative incidences for progression to a malignant category (LR-5 or LR-M) and LR-4 or higher were calculated for each baseline category and compared using log-rank tests. Clinical variables and imaging features significantly predictive of progression to a malignant category were evaluated using Cox proportional hazards modelling. RESULTS: The 162 observations were initially categorized into 60 LR-2, 75 LR-3 and 27 LR-4. For LR-4 observations, the 1-year, 3-year and 5-year cumulative incidences of progression to a malignant category were 18.5% (95% confidence interval, 6.6-35.2%), 43.0% (23.1-61.5%) and 52.5% (25.9-73.5%), which were significantly higher than those of LR-2 and LR-3 (p < .001). For LR-3, the 1-year, 3-year and 5-year cumulative incidences of progression to LR-4 or higher were 4.1% (1.1-10.4%), 13.9% (6.7-23.6%) and 23.1% (12.7-35.4%), which were significantly higher than that of LR-2 (p  = .009). In multivariable analysis, size ≥1.0 cm (hazard ratio [HR] = 2.58, 1.04-6.40) and nonrim arterial-phase hyperenhancement (HR = 2.45, 1.11-5.42) were significantly independently associated with progression to a malignant category. CONCLUSION: Long-term imaging outcomes differed significantly according to LI-RADS category. Size ≥1.0 cm and nonrim arterial-phase hyperenhancement were imaging features significantly predictive of progression to a malignant category.

Preoperative magnetic resonance imaging-based prognostic model for mass-forming intrahepatic cholangiocarcinoma.

BACKGROUND & AIMS: As most staging systems for intrahepatic cholangiocarcinoma (iCCA) are based on pathological results, preoperative prognostic prediction is limited. This study aimed to develop and validate a prognostic model for the overall survival of patients with mass-forming iCCA (MF-iCCA) using preoperative magnetic resonance imaging (MRI) and clinical findings. METHODS: We enrolled a total of 316 patients who underwent preoperative MRI and surgical resection for treatment-naive MF-iCCA from six institutions, between January 2009 and December 2015. The subjects were randomly assigned to a training set (n = 208) or validation set (n = 108). The MRIs were independently reviewed by three abdominal radiologists. Using MRI and clinical findings, an MRI prognostic score was established. We compared the discrimination performance of MRI prognostic scores with those of conventional pathological staging systems. RESULTS: We developed an MRI prognostic score consisting of serum CA19-9 and three MRI findings (tumour multiplicity, lymph node metastasis and bile duct invasion). The MRI prognostic score demonstrated good discrimination performance in both the training set (C-index, 0.738; 95% confidence interval [CI], 0.698-0.780) and validation set (C-index, 0.605; 95% CI, 0.526-0.680). In the validation set, MRI prognostic score showed no significant difference with AJCC 8th TNM stage, MEGNA score and Nathan's stage. CONCLUSIONS: Our MRI prognostic score for overall survival of MF-iCCA showed comparable discriminatory performance with pathological staging systems and might be used to determine an optimal treatment strategy.