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).

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.

Radiofrequency ablation of subcapsular versus nonsubcapsular hepatocellular carcinomas ≤ 3 cm: analysis of long-term outcomes from two large-volume liver centers.

OBJECTIVES: To compare the safety and efficacy of RFA for single HCCs ≤ 3 cm in subcapsular versus nonsubcapsular locations using a propensity score matched analysis. MATERIALS AND METHODS: This retrospective study included patients with solitary HCCs ≤ 3 cm in size who underwent percutaneous RFA from 2005 to 2015 as initial treatment at two large-volume liver centers. Patients were divided into two groups, consisting of those with subcapsular and nonsubcapsular tumor locations. Complications, local tumor progression (LTP), and overall survival (OS) were compared in these two groups before and after propensity score matching (PSM). RESULTS: The study population consisted of 964 patients (712 men [74%]) of mean age 58.3 years. Of these 964 patients, 561 (58%) had nonsubcapsular and 403 (42%) had subcapsular HCCs. PSM generated 402 pairs of patients. Major complication rate was low, but significantly higher in the subcapscular group (p = 0.047). Rates of technical effectiveness in these two groups were 99% and 98%, respectively (p = 0.315). However, during follow-up, cumulative 1-, 3-, 5-, and 10-year LTP and OS rates did significantly differ in both entire and PSM cohorts, resulting in the latter 8%, 15%, 20%, and 26% in the nonsubcapsular group vs. 13%, 24%, 30%, and 31% in the subcapsular group (p = 0.015), and 99%, 91%, 80%, and 59% vs. 98%, 85%, 73%, and 50% in the two groups (p = 0.004), respectively. CONCLUSION: Rates of major complications, LTP, and OS differed significantly following first-line RFA treatment of single HCCs ≤ 3 cm in favor of the nonsubcapsular locations. CLINICAL RELEVANCE STATEMENT: This large-scale study provides evidence that radiofrequency ablation for small (≤ 3 cm) hepatocellular carcinomas is safer and more effective in nonsubcapsular location than in subcapsular location. KEY POINTS: • There exist conflicting outcomes on the effectiveness of RFA for early HCC depending on tumor location. • Rate of local tumor progression was significantly higher in the subcapsular hepatocellular carcinomas. • Overall survival rate was significantly poorer in the subcapsular hepatocellular carcinomas.

Chemoembolization versus radiofrequency ablation for single small (≤ 3 cm) hepatocellular carcinoma: a propensity score matching analysis.

OBJECTIVES: To compare the efficacy of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for patients with single small (≤ 3 cm) hepatocellular carcinoma (HCC) and preserved liver function (Child-Pugh class A). MATERIALS AND METHODS: The clinical features of treatment-naïve patients who underwent TACE and RFA as first-line treatment were balanced through propensity score matching (PSM). The primary endpoint was overall survival (OS), and the secondary endpoints were local tumor recurrence (LTR) and recurrence-free survival (RFS). RESULTS: The analysis included 440 patients who received TACE, and 430 patients who received RFA. After PSM adjustment (323 pairs), the 5- and 10-year OS rates were 81% and 61%, respectively, in patients who underwent RFA, and 77% and 51%, respectively, for patients who underwent TACE (p = 0.021). Subgroup analyses showed that OS, LTR, and RFS were homogeneously better in the RFA group. CONCLUSION: RFA was associated with better survival outcomes than TACE in patients with single small HCC and preserved liver function. CLINICAL RELEVANCE STATEMENT: This large-scale comparative study provides evidence that radiofrequency ablation has a better overall survival rate than chemoembolization for small (≤ 3 cm) hepatocellular carcinomas. KEY POINTS: • The relative effectiveness of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for early HCC is unclear. • Overall survival rate was significantly higher in the RFA group. • The effects of RFA on overall survival, local tumor recurrence, and recurrence-free survival were homogeneously better in all subgroups.

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.

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.

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.

Thermal ablation in the treatment of intrahepatic cholangiocarcinoma: a systematic review and meta-analysis.

OBJECTIVE: To summarize the efficacy and safety of thermal ablation for the treatment of intrahepatic cholangiocarcinoma (ICC). METHODS: MEDLINE, EMBASE, Cochran Library, and Web of Science databases were searched for studies reporting outcomes in patients with ICC treated with thermal ablation. Meta-analyses of cumulative overall survival (OS) and recurrence-free survival (RFS), Kaplan-Meier survival rates according to time to local tumor progression (TTLTP), technical efficacy, and incidence of complications were analyzed. Pooled hazard ratios of common variables were calculated to explore factors associated with OS. RESULTS: Twenty observational studies comprising 917 patients were reviewed (primary ICC [n = 502]; post-surgical recurrent ICC [n = 355]; information not available [n = 60]). The pooled proportion of technical efficacy was 91.9% (95% CI, 87.3-94.9%). The pooled 1-, 3-, and 5-year OS rates were 82.4% (95% CI, 75.1-88.9%), 42.1% (95% CI, 36.0-48.4%), and 28.5% (95% CI, 21.2-36.2%). Primary tumors showed higher 3-year OS rates than recurrent ones, with borderline significance (p = 0.072). The pooled 1- and 3-year RFS rates were 40.0% (95% CI, 33.6-46.4%) and 19.2% (95% CI, 8.4-32.7%). The pooled 1-, 3-, and 5-year TTLTP rates were 79.3% (95% CI, 65.1-90.9%), 59.5% (95% CI, 49.1-69.4%), and 58.2% (95% CI, 44.9-70.9%). The pooled incidence of major complications was 5.7% (95% CI, 4.1-7.8%). Tumor size (> 3 cm), multiple tumors, and age (> 65 years) were factors associated with shorter OS. CONCLUSION: Thermal ablation is a successful alternative with a good safety profile, especially for a single ICC smaller than 3 cm. KEY POINTS: • The pooled 1-, 3-, and 5-year OS rates following thermal ablation for the treatment of intrahepatic cholangiocarcinoma were 82.4%, 42.1%, and 28.5%. • The pooled incidence of major complications was 5.7%. • A tumor size > 3 cm (HR: 2.12, p = 0.006), multiple tumors (HR: 1.67, p = 0.004), and age > 65 years (HR: 1.67, p = 0.006) were factors associated with shorter OS.

Percutaneous Radiofrequency Ablation for Recurrent Intrahepatic Cholangiocarcinoma After Curative Resection: Multivariable Analysis of Factors Predicting Survival Outcomes.

OBJECTIVE. The purpose of this study was to evaluate the factors associated with local tumor progression (LTP) and overall survival (OS) in patients who have undergone percutaneous radiofrequency ablation (RFA) for recurrent intrahepatic cholangiocarcinoma (iCCA) after curative resection. MATERIALS AND METHODS. Data from 40 patients (mean age, 56.3 years) with 64 recurrent iCCAs (median diameter, 1.5 cm) who underwent percutaneous RFA between 1999 and 2019 were retrospectively analyzed. Patients were included if they had three or fewer metastases, a maximum tumor diameter of 5 cm or less, and disease confined to the liver. RESULTS. Technical success was achieved in all patients, with no procedure-related mortality. During follow-up, local progression of treated lesions was observed in 31.3% of tumors. The median OS and 5-year survival rate from initial RFA were 26.6 months and 18.3%, respectively. Multivariable analysis showed that a larger tumor diameter (> 2 cm, p = .004) was significantly associated with reduced LTP-free survival and that both a larger tumor diameter and less than 1 year from surgery to recurrence (p = .005 and .006, respectively) were statistically significant predictors of reduced OS after RFA. CONCLUSION. Percutaneous RFA may offer a well-tolerated and successful approach to local tumor control in patients with recurrent iCCA after curative surgery. Patients with a small-diameter tumor (≤ 2 cm) and late hepatic recurrence (≥ 1 year after curative resection) benefited most from RFA treatment.

Radiofrequency ablation versus stereotactic body radiation therapy for small (≤ 3 cm) hepatocellular carcinoma: A retrospective comparison analysis.

BACKGROUND AND AIM: We compared the clinical outcomes of radiofrequency ablation (RFA) and stereotactic body radiation therapy (SBRT) in small (≤ 3 cm) hepatocellular carcinoma. METHODS: A total of 266 patients treated with RFA (n = 179) or SBRT (n = 87) were reviewed. Local control rates (LCRs), intrahepatic recurrence-free survival (IHRFS) rates, and overall survival (OS) rates were compared. Inverse probability of treatment weighting (IPTW) was used to adjust for imbalances in baseline characteristics between the two groups. RESULTS: The median follow-up period was 50.3 months, and treatment method (RFA vs SBRT) was not a significant prognostic factor for LCR, OS, and IHRFS in both multivariate and IPTW-adjusted analyses. The 4-year LCRs after RFA and SBRT were 92.7% and 95.0%, respectively. Perivascular location was a significant prognostic factor for LCR in the entire patients and in the RFA group, but not in the SBRT group. The 4-year OS rates in the RFA and SBRT groups were 78.1% and 64.1%, respectively (P = 0.012). After IPTW adjustment, the 4-year LCRs (90.6% vs 96.3%) and OS rates (71.8% vs 70.2%) were not significantly different between the two groups. The rate of grade ≥ 3 adverse events was 0.6% (n = 1) in the RFA group and 1.1% (n = 1) in the SBRT group. CONCLUSIONS: The two treatment methods showed comparable outcomes in terms of LCR, OS rate, and IHRFS rate after IPTW adjustment. SBRT seems to be a viable alternative method for small hepatocellular carcinomas that are not suitable for RFA due to tumor location.

Liver imaging reporting and data system category M: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The Liver Imaging Reporting and Data System (LI-RADS) category M (LR-M) was introduced to preserve the high specificity of LI-RADS algorithm for diagnosing hepatocellular carcinoma (HCC). We aimed to systematically determine the probability of the LR-M for HCC and non-HCC malignancy, and to determine the sources of heterogeneity between reported results. METHODS: Original studies reporting the probability of LR-M for HCC and non-HCC malignancy on magnetic resonance imaging (MRI) were identified in MEDLINE and EMBASE. The meta-analytic pooled percentages of HCC and non-HCC in LR-M were calculated. Meta-regression analysis was performed to explore study heterogeneity. The meta-analytic frequency of each LR-M imaging feature was determined. RESULTS: We found 10 studies reporting the diagnostic performance of LR-M (1819 lesions in 1631 patients), and six reporting the frequency of LR-M imaging features. The pooled percentages of HCC and non-HCC malignancy for LR-M were 28.2% (95% confidence interval [CI], 23.8%-33.1%; I2  = 83%) and 69.6% (95% CI, 64.6%-74.1%; I2  = 83%) respectively. The study type and MRI scanner field strength were significantly associated with study heterogeneity (P ≤ .04). Of the seven imaging features, rim arterial phase hyperenhancement showed the highest frequency in both non-HCC (48.9%; 95% CI, 43.0%-54.8%) and HCC groups (9.8%; 95% CI, 6.9%-13.6%). CONCLUSIONS: The LR-M category most commonly included non-HCC malignancy but also included 28.2% of HCC. Substantial study heterogeneity was noted, and it was significantly associated with study type and MRI scanner field strength. In addition, the frequency of LR-M imaging features was variable.

Ancillary features in the Liver Imaging Reporting and Data System: how to improve diagnosis of hepatocellular carcinoma ≤ 3 cm on magnetic resonance imaging.

OBJECTIVES: To determine the strength of association with hepatocellular carcinoma (HCC) of each ancillary feature (AF) in LI-RADS version 2018, and to develop an appropriate strategy for applying AFs to improve the diagnosis of HCC ≤ 3 cm on gadoxetate-enhanced MRI. METHODS: A total of 385 nodules (283 HCCs, 18 non-HCC malignancies, 84 benign nodules) of ≤ 3 cm in 266 patients at risk for HCC who underwent gadoxetate-enhanced MRI in 2016 were retrospectively evaluated. Two radiologists independently evaluated the presence/absence of AFs, and assigned a LI-RADS category to each nodule. Diagnostic odds ratio (DOR) of each AF was assessed. To improve the diagnostic performance for HCC, various criteria were developed based on the number of AFs favoring malignancy in general or HCC in particular. Generalized estimating equation models were used to compare the diagnostic performance of each criterion with that of the major features (MFs) only. RESULT: All AFs favoring HCC in particular and malignancy in general were more common in the HCC group than in the non-HCC group. Of these AFs, hepatobiliary-phase hypointensity had the strongest association with HCC (DOR, 21.82; 95% confidence interval, 5.59-85.20). When we applied AFs in addition to MFs, the new criterion (with a number of AFs ≥ 4) had significantly higher sensitivity (80.6% vs. 70.0%; p < 0.001) than MFs only, without significant lower specificity (85.3% vs. 90.2%; p = 0.060). CONCLUSIONS: The AFs varied in the strengths of association with HCC. More strict application of AFs (AFs ≥ 4) in LR-3 may improve the diagnostic performance for probable HCC ≤ 3 cm. KEY POINTS: • The ancillary features (AFs) in the Liver Imaging Reporting and Data System version 2018 showed variable frequencies of occurrence and strengths of association with hepatocellular carcinoma (HCC). • Of the various AFs, hepatobiliary-phase hypointensity had the highest frequency and strongest association with HCC on gadoxetate disodium-enhanced MRI. • When applying AFs in addition to major features, a criterion of four or more AFs significantly increased the sensitivity for diagnosing HCC, without a significantly decreased specificity, especially in LR-3 observations.

Arterial subtraction images of gadoxetate-enhanced MRI improve diagnosis of early-stage hepatocellular carcinoma.

BACKGROUND & AIMS: Although gadoxetate disodium-enhanced magnetic resonance imaging (MRI) shows higher sensitivity for diagnosing hepatocellular carcinoma (HCC), its arterial-phase images may be unsatisfactory because of weak arterial enhancement. We investigated the clinical effectiveness of arterial subtraction images from gadoxetate disodium-enhanced MRI for diagnosing early-stage HCC using the Liver Imaging Reporting and Data System (LI-RADS) v2018. METHODS: In 258 patients at risk of HCC who underwent gadoxetate disodium-enhanced MRI in 2016, a total of 372 hepatic nodules (273 HCCs, 18 other malignancies, and 81 benign nodules) of 3.0 cm or smaller were retrospectively analyzed. Final diagnosis was assessed histopathologically or clinically (marginal recurrence after treatment or change in lesion size on follow-up imaging). The detection rate for arterial hyperenhancement was compared between ordinary arterial-phase and arterial subtraction images, and the benefit of arterial subtraction images in diagnosing HCC using LI-RADS was assessed. RESULTS: Arterial subtraction images had a significantly higher detection rate for arterial hyperenhancement than ordinary arterial-phase images, both for all hepatic nodules (72.3% vs. 62.4%, p <0.001) and HCCs (91.9% vs. 80.6%, p <0.001). Compared with ordinary arterial-phase images, arterial subtraction images significantly increased the sensitivity of LI-RADS category 5 for diagnosis of HCC (64.1% [173/270] vs. 55.9% [151/270], p <0.001), without significantly decreasing specificity (92.9% [91/98] vs. 94.9% [93/98], p = 0.155). For histopathologically confirmed lesions, arterial subtraction images significantly increased sensitivity to 68.8% (128/186) from the 61.3% (114/186) of ordinary arterial-phase images (p <0.001), with a minimal decrease in specificity to 84.8% (39/46) from 89.1% (41/46) (p = 0.151). CONCLUSIONS: Arterial subtraction images of gadoxetate disodium-enhanced MRI can significantly improve the sensitivity of early-stage HCC diagnosis using LI-RADS, without a significant decrease in specificity. LAY SUMMARY: Gadoxetate disodium-enhanced magnetic resonance imaging is an imaging technique with a high sensitivity for the diagnosis of hepatocellular carcinoma. However, arterial-phase images may be unsatisfactory because of weak arterial enhancement. We found that using arterial subtraction images led to clinically meaningful improvements in the diagnosis of early-stage hepatocellular carcinoma.

LI-RADS Classification and Prognosis of Primary Liver Cancers at Gadoxetic Acid-enhanced MRI.

Purpose To (a) evaluate the postsurgical prognostic implication of the Liver Imaging Reporting and Data System (LI-RADS) categories of primary liver cancers and (b) determine the performance of LI-RADS version 2017 in differentiating hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma (IHCC) and combined hepatocellular-cholangiocarcinoma (cHCC-CC) at gadoxetic acid-enhanced MRI. Materials and Methods In this retrospective study, 194 patients with cirrhosis and surgically proven single primary liver cancer (53 with cHCC-CC, 44 with IHCC, and 97 with HCC) were evaluated with gadoxetic acid-enhanced MRI between 2009 and 2014. The mean patient age was 57 years (age range, 30-83 years). There were 155 men with a mean age of 56 years (range, 30-81 years) and 39 women with a mean age of 58 years (range, 38-83 years). Two independent readers assigned an LI-RADS category for each nodule. Overall survival (OS), recurrence-free survival (RFS), and their associated factors were evaluated by using the Kaplan-Meier method, log-rank test, and Cox proportional hazard model. Results In the multivariable analysis, the LI-RADS category was an independent factor for OS (hazard ratio, 4.2; P < .001) and RFS (hazard ratio, 2.6; P = .01). The LR-M category showed more correlation with poorer OS and RFS than did the LR-4 or LR-5 category for all primary liver cancers (P < .001 for both), HCCs (P = .01 and P < .001, respectively), and cHCC-CCs (P = .01 and P = .03, respectively). The LR-5 category had a sensitivity of 69% (67 of 97) and a specificity of 87% (84 of 97) in the diagnosis of HCC; most false-positive diagnoses (85%, 11 of 13) were the result of misclassification of cHCC-CCs. Conclusion The Liver Imaging Reporting and Data System (LI-RADS) category was associated with postsurgical prognosis of primary liver cancers, independent of pathologic diagnosis. The LI-RADS enabled the correct classification of most hepatocellular carcinomas (HCCs) and intrahepatic cholangiocarcinomas, whereas differentiation of combined hepatocellular-cholangiocarcinoma from HCC was unreliable. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Bashir and Chernyak in this issue.

Radiomics Analysis of Gadoxetic Acid-enhanced MRI for Staging Liver Fibrosis.

Purpose To develop and validate a radiomics-based model for staging liver fibrosis by using gadoxetic acid-enhanced hepatobiliary phase MRI. Materials and Methods In this retrospective study, 436 patients (mean age, 51 years; age range, 18-86 years; 319 men [mean age, 51 years; age range, 18-86 years]; 117 women [mean age, 50 years; age range, 18-79 years]) with pathologic analysis-proven liver fibrosis who underwent gadoxetic acid-enhanced MRI from June 2015 to December 2016 were randomized in a three-to-one ratio into development (n = 329) and test (n = 107) cohorts, respectively. In the development cohort, a model was developed to calculate radiomics fibrosis index (RFI) by using logistic regression with elastic net regularization to differentiate stage F3-F4 from stage F0-F2. Optimal RFI cutoffs to diagnose clinically significant fibrosis (stage F2-F4), advanced fibrosis (stage F3-F4), and cirrhosis (stage F4) were determined by receiver operating characteristic curve analysis. In the test cohort, the diagnostic performance of RFI was compared with that of normalized liver enhancement, aspartate transaminase-to-platelet ratio index (APRI), and fibrosis-4 index by using the Obuchowski index. Results In the test cohort, RFI (Obuchowski index, 0.86) significantly outperformed normalized liver enhancement (Obuchowski index, 0.77; P < .03), APRI (Obuchowski index, 0.60; P < .001), and fibrosis-4 index (Obuchowski index, 0.62; P < .001) for staging liver fibrosis. By using the cutoffs, RFI had sensitivities and specificities as follows: 81% (95% confidence interval: 71%, 89%) and 78% (95% confidence interval: 63%, 89%) for diagnosing stage F2-F4, respectively; 79% (95% confidence interval: 67%, 88%) and 82% (95% confidence interval: 69%, 91%), respectively, for diagnosing stage F3-F4; and 92% (95% confidence interval: 79%, 98%) and 75% (95% confidence interval: 62%, 83%), respectively, for diagnosing stage F4. Conclusion Radiomics analysis of gadoxetic acid-enhanced hepatobiliary phase images allows for accurate diagnosis of liver fibrosis. © RSNA, 2018 Online supplemental material is available for this article.

Clinical Outcomes of Radiofrequency Ablation for Early Hypovascular HCC: A Multicenter Retrospective Study.

Purpose To retrospectively evaluate the clinical outcomes of radiofrequency ablation (RFA) for early hypovascular hepatocellular carcinomas (HCCs) and to compare them with those of typical hypervascular HCCs. Materials and Methods This retrospective multicenter study received institutional review board approval, with a waiver of the need to obtain informed consent. A total of 56 patients (male-to-female ratio, 40:16; mean age, 61.8 years; age range, 33-87 years) with pathologically proven early HCCs that did not meet the noninvasive diagnosis criteria and who were initially treated with RFA at one of five university-affiliated hospitals between January 2009 and December 2013 comprised the study group. Thereafter, 240 patients with hypervascular HCCs initially treated with RFA in the same period in a historical cohort were selected as control patients. Overall survival (OS), progression-free survival (PFS), and cumulative incidence of local tumor progression (LTP) were estimated by using Kaplan-Meier analysis and were compared by using the Cox proportional hazard regression model. After the first analysis, propensity score analysis was performed to reduce potential bias. Results Complete ablation was achieved in all 56 patients with early hypovascular HCCs after RFA. The estimated 5-year cumulative incidence of LTP in the 56 patients with early hypovascular HCCs was significantly lower than in the 240 patients with hypervascular HCCs (5.4% for early hypovascular HCCs vs 20.8% for hypervascular HCCs; hazard ratio = 6.57 [95% confidence interval: 1.59, 27.2]; P = .009). After propensity matching, the estimated 5-year cumulative incidence of LTP in patients with early hypovascular HCCs was still significantly lower than that in patients with hypervascular HCCs (5.4% vs 23.0%; P = .025; hazard ratio = 5.71 [95% confidence interval: 1.27, 25.8]). OS was not significantly different between the groups (P = .100). One-year PFS in the 56 patients with early hypovascular HCCs, on the other hand, appeared to be favorable at 92.7%, compared with 79.4% in the 240 patients with hypervascular HCCs, but overall, PFS was not significantly different (P = .066). Conclusion RFA of early hypovascular HCCs provided similar OS and PFS compared with RFA of typical hypervascular HCCs, despite its significantly lower 5-year cumulative incidence of LTP. © RSNA, 2017 Online supplemental material is available for this article.

Liver Imaging Reporting and Data System: Patient Outcomes for Category 4 and 5 Nodules.

Purpose To determine the outcomes after initial therapy in patients with chronic liver disease and retrospectively assigned Liver Imaging Reporting and Data System (LI-RADS; version 2014) category 4 (LR-4) and 5 (LR-5) nodules at gadoxetate disodium-enhanced MR imaging. Materials and Methods In this retrospective study, 260 patients with a single LR-4 (n = 132) or LR-5 (n = 128) nodule who were assigned a LI-RADS category were included. Patients were identified between January 2012 and December 2012, and were initially treated by resection, liver transplant, radiofrequency ablation (RFA), or transcatheter arterial chemoembolization (TACE) according to the Barcelona Clinic Liver Cancer staging system. Follow-up continued until August 31, 2016. The incidences of local tumor recurrence (ILRs) and distant tumor recurrence (IDRs) and recurrence-free survival (RFS) were compared between the LR-4 and LR-5 patients. For each category, ILRs, IDRs, and RFS were compared across the four treatments. Results LR-5 patients were more frequently treated by surgical resection than LR-4 patients (72.7% [93 of 128] vs 41.7% [55 of 132], respectively; P < .001), but less frequently treated by RFA (19.5% [25 of 128] vs 30.3% [40 of 132], respectively; P = .047) and TACE (6.3% [eight of 128] vs 22.0% [29 of 132], respectively; P < .001). ILRs and IDRs were not significantly different between LR-4 and LR-5 patients according to the type of treatment (0%-48.3% [14 of 29] vs 0%-25.0% [two of eight], P $ .423; 0%-55.2% [16 of 29] vs 0%-37.5% [three of eight], P $ .447, respectively). There was no difference in RFS between the two categories (36.3 months vs 41.7 months, respectively; P = .084). Liver transplant showed no local or distant tumor recurrence in either category. Resection showed higher RFS and lower ILR and IDR than RFA and TACE in both LR-4 and LR-5 patients. Conclusion Patients with LR-4 nodules had ILRs and IDRs similar to patients with LR-5 nodules when stratified by treatment type. RFS was also similar between patients with LR-4 and LR-5 nodules. Among the four initial treatments, liver transplant and resection showed better local tumor control, with longer RFS than RFA or TACE. © RSNA, 2018 Online supplemental material is available for this article.

Utility and Safety of Repeated Ultrasound-Guided Core Needle Biopsy of Focal Liver Masses.

OBJECTIVES: To evaluate the accuracy and safety of repeated ultrasound-guided core needle biopsy (CNB) for hepatic focal lesions and to assess the predictive factors for success of repeated CNB. METHODS: For 5 years, 3085 CNBs were performed for focal hepatic lesions using an automated biopsy gun with an 18-gauge needle. Seventy-eight patients underwent repeated CNB because of pathologically inconclusive or unexpected results. Twelve patients were excluded because of unavailable additional tissue or follow-up imaging by radiofrequency ablation (n = 5), repeated CNB greater than than 3 months after the first CNB (n = 5), and insufficient follow-up time (n = 2). Sixty-six patients were finally enrolled after the exclusion criteria were applied. We retrospectively evaluated tumor necrosis, tumor size, number of passes, lesion site, depth, tumor conspicuity, and complications. Continuous data and the total scores of the grading system were analyzed by the Student t test, and categorical data and each category were analyzed by the Fisher exact test. RESULTS: The repeated CNB rate was 2.5% (78 of 3085). The diagnostic accuracy of the repeated biopsies was 83.3% (55 of 66). Comparing the diagnostic group with the nondiagnostic group, no variable (ie, size, depth, necrosis, lesion site [segment], and number of passes) had a statistically significant difference. Tumor conspicuity was a significant factor for predicting successful repeated biopsy (P < .001). The cumulative complication rate was 10.6% (7 of 66), with only minor complications. CONCLUSIONS: Repeated CNB is an accurate and safe procedure for obtaining a histologic diagnosis of hepatic focal lesions if the initial biopsy fails. High tumor conspicuity showed a significant correlation with successful repeated CNB.

Combined hepatocellular-cholangiocarcinoma: Gadoxetic acid-enhanced MRI findings correlated with pathologic features and prognosis.

PURPOSE: To evaluate gadoxetic acid-enhanced magnetic resonance imaging (MRI) findings of combined hepatocellular cholangiocarcinoma (cHCC-CC) with special emphasis on correlation of MRI findings with histopathologic tumor characteristics and survival outcomes after curative surgery. MATERIALS AND METHODS: Our Institutional Review Board approved this study, with a waiver of informed consent. For 82 patients (64 men, 18 women; mean age, 54.0 years; age range, 30-81) with surgically confirmed cHCC-CCs, we evaluated clinical features, histologic findings, and tumor morphologic and enhancement features on gadoxetic acid-enhanced liver MRI at 1.5T (n = 67) or 3.0T (n = 15). Imaging features of cHCC-CCs were correlated with pathologic findings according to the 2010 World Health Organization classification system. Tumors were categorized as hypervascular or nonhypervascular based on arterial phase enhancement and were compared with respect to overall and recurrence-free survival after curative-intent surgery. RESULTS: Of the 82 lesions, 48 showing global arterial phase enhancement were categorized as the hypervascular group, while 34 lesions demonstrating rim, peripheral, or isoenhancement were categorized as the nonhypervascular group. There was no significant difference in MRI findings between pathologic tumor types (classical type versus stem cell feature type, P = 0.324-1.0). Compared with the nonhypervascular group, the hypervascular group had a larger HCC component (P = 0.014), smaller CC component (P = 0.001), and lesser amount of fibrotic stroma (P = 0.006) on pathologic analysis and was an independent factor associated with better overall survival after surgical resection (P = 0.033). CONCLUSION: Gadoxetic acid-enhanced MRI findings of cHCC-CCs were diverse, reflecting heterogeneous histologic features. The hypervascular group on MRI is associated with a larger HCC component, smaller CC component, less fibrotic stroma, and better overall survival after curative surgery than the nonhypervascular group. LEVEL OF EVIDENCE: 4 J. MAGN. RESON. IMAGING 2017;46:267-280.