Efficacy of GV1001 with gemcitabine/capecitabine in previously untreated patients with advanced pancreatic ductal adenocarcinoma having high serum eotaxin levels (KG4/2015): an open-label, randomised, Phase 3 trial.

BACKGROUND: The TeloVac study indicated GV1001 did not improve the survival of advanced pancreatic ductal adenocarcinoma (PDAC). However, the cytokine examinations suggested that high serum eotaxin levels may predict responses to GV1001. This Phase III trial assessed the efficacy of GV1001 with gemcitabine/capecitabine for eotaxin-high patients with untreated advanced PDAC. METHODS: Patients recruited from 16 hospitals received gemcitabine (1000 mg/m2, D 1, 8, and 15)/capecitabine (830 mg/m2 BID for 21 days) per month either with (GV1001 group) or without (control group) GV1001 (0.56 mg; D 1, 3, and 5, once on week 2-4, 6, then monthly thereafter) at random in a 1:1 ratio. The primary endpoint was overall survival (OS) and secondary end points included time to progression (TTP), objective response rate, and safety. RESULTS: Total 148 patients were randomly assigned to the GV1001 (n = 75) and control groups (n = 73). The GV1001 group showed improved median OS (11.3 vs. 7.5 months, P = 0.021) and TTP (7.3 vs. 4.5 months, P = 0.021) compared to the control group. Grade >3 adverse events were reported in 77.3% and 73.1% in the GV1001 and control groups (P = 0.562), respectively. CONCLUSIONS: GV1001 plus gemcitabine/capecitabine improved OS and TTP compared to gemcitabine/capecitabine alone in eotaxin-high patients with advanced PDAC. CLINICAL TRIAL REGISTRATION: NCT02854072.

Radiomics model versus 2017 revised international consensus guidelines for predicting malignant intraductal papillary mucinous neoplasms.

OBJECTIVES: To evaluate a CT-based radiomics model for identifying malignant pancreatic intraductal papillary mucinous neoplasms (IPMNs) and compare its performance with the 2017 international consensus guidelines (ICGs). MATERIALS AND METHODS: We retrospectively included 194 consecutive patients who underwent surgical resection of pancreatic IPMNs between January 2008 and December 2020. Surgical histopathology was the reference standard for diagnosing malignancy. Using radiomics features from preoperative contrast-enhanced CT, a radiomics model was built with the least absolute shrinkage and selection operator by a five-fold cross-validation. CT and MR images were independently reviewed based on the 2017 ICGs by two abdominal radiologists, and the performances of the 2017 ICGs and radiomics model were compared. The areas under the curve (AUCs) were compared using the DeLong method. RESULTS: A total of 194 patients with pancreatic IPMNs (benign, 83 [43%]; malignant, 111 [57%]) were chronologically divided into training (n = 141; age, 65 ± 8.6 years; 88 males) and validation sets (n = 53; age, 66 ± 9.7 years; 31 males). There was no statistically significant difference in the diagnostic performance of the 2017 ICGs between CT and MRI (AUC, 0.71 vs. 0.71; p = 0.93) with excellent intermodality agreement (k = 0.86). In the validation set, the CT radiomics model had higher AUC (0.85 vs. 0.71; p = 0.038), specificity (84.6% vs. 61.5%; p = 0.041), and positive predictive value (84.0% vs. 66.7%; p = 0.044) than the 2017 ICGs. CONCLUSION: The CT radiomics model exhibited better diagnostic performance than the 2017 ICGs in classifying malignant IPMNs. CLINICAL RELEVANCE STATEMENT: Compared with the radiologists' evaluation based on the 2017 international consensus guidelines, the CT radiomics model exhibited better diagnostic performance in classifying malignant intraductal papillary mucinous neoplasms. KEY POINTS: • There is a paucity of comparisons between the 2017 international consensus guidelines (ICGs) and radiomics models for malignant intraductal papillary mucinous neoplasms (IPMNs). • The CT radiomics model developed in this study exhibited better diagnostic performance than the 2017 ICGs in classifying malignant IPMNs. • The radiomics model may serve as a valuable complementary tool to the 2017 ICGs, potentially allowing a more quantitative assessment of IPMNs.

Steatotic hepatocellular carcinoma: Association of MRI findings to underlying liver disease and clinicopathological characteristics.

BACKGROUND & AIMS: Fatty change is commonly observed in hepatocellular carcinoma (HCC); however, the characteristics of steatotic and steatohepatitic HCCs are not well understood. METHODS: This retrospective study included patients with HCCs who underwent resection between January 2014 and December 2019 to evaluate clinicopathological and magnetic resonance imaging features. Tumours were categorized as magnetic resonance imaging-steatotic, pathology-steatotic and steatohepatitic HCCs and were defined as HCCs with ≥50% steatosis on in-and-oppose phase images, ≥34% tumour cells with lipid droplets and ≥50% tumour areas with steatohepatitic features on light microscopy respectively. RESULTS: Of 465 HCCs, 38 (8%), 23 (5%) and 15 (3%) were diagnosed as magnetic resonance imaging-steatotic, pathology-steatotic and steatohepatitic HCCs respectively. These HCC variants were less likely to be associated with hepatitis B virus infections than with type 2 diabetes mellitus, metabolic syndrome, non-tumour liver steatosis and steatohepatitis. Moreover, microvascular invasion was less likely to be associated with them than either tumour size or differentiation. Type 2 diabetes and non-tumour steatosis were independent risk factors for magnetic resonance imaging-steatotic HCCs. Pathology-steatotic HCCs and steatohepatitic HCCs were significantly associated with magnetic resonance imaging-steatotic HCCs. A targetoid appearance in the transitional or hepatobiliary phase was also more prevalent in steatohepatitic-HCCs than in non-steatohepatitic-HCCs. When magnetic resonance imaging-steatotic HCCs were combined with one or more ancillary features, the sensitivity and specificity were 60% and 97% respectively. CONCLUSION: Underlying fatty liver disease and metabolic syndrome are strongly associated with both steatotic and steatohepatitic HCCs. Clinicoradiological characteristics help identify steatohepatitic HCC with high specificity.

Comparison of imaging findings of macrotrabecular-massive hepatocellular carcinoma using CT and gadoxetic acid-enhanced MRI.

OBJECTIVES: To investigate the imaging findings of macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) on CT and MRI, and examine their diagnostic performance and prognostic significance. METHODS: We retrospectively enrolled 220 consecutive patients who underwent hepatic resection between June 2009 and December 2013 for single treatment-naïve HCC, who have preoperative CT and gadoxetic acid-enhanced MRI. Independent reviews of histopathology and imaging were performed by two reviewers. Previously reported imaging findings, LI-RADS category, and CT attenuation of MTM-HCC were investigated. The diagnostic performance of the MTM-HCC diagnostic criteria was compared across imaging modalities. RESULTS: MTM-HCC was associated with ≥ 50% arterial phase hypovascular component, intratumoral artery, arterial phase peritumoral enhancement, and non-smooth tumor margin on CT and MRI (p < .05). Arterial phase hypovascular components were less commonly observed on MRI subtraction images than on CT or MRI, while non-rim arterial phase hyperenhancement and LR-5 were more commonly observed on MRI subtraction images than on MRI (p < .05). MTM-HCC showed lower tumor attenuation in the CT arterial phase (p = .01). Rhee's criteria, defined as ≥ 50% hypovascular component and ≥ 2 ancillary findings (intratumoral artery, arterial phase peritumoral enhancement, and non-smooth tumor margin), showed similar diagnostic performance for MRI (sensitivity, 41%; specificity, 97%) and CT (sensitivity, 31%; specificity, 94%). Rhee's criteria on CT were independent prognostic factors for overall survival. CONCLUSION: The MRI diagnostic criteria for MTM-HCC are applicable on CT, showing similar diagnostic performance and prognostic significance. For MTM-HCC, arterial phase subtraction images can aid in the HCC diagnosis by depicting subtle arterial hypervascularity. KEY POINTS: • MTM-HCC on CT demonstrated previously described MRI findings, including arterial phase hypovascular component, intratumoral artery, arterial phase peritumoral enhancement, and necrosis. • The MRI diagnostic criteria for MTM-HCC were also applicable to CT, showing comparable diagnostic performance and prognostic significance. • On arterial phase subtraction imaging, MTM-HCC more frequently demonstrated non-rim enhancement and LR-5 and less frequently LR-M than MRI arterial phase, which may aid in the diagnosis of HCC.

Optimal imaging criteria and modality to determine Milan criteria for the prediction of post-transplant HCC recurrence after locoregional treatment.

OBJECTIVES: We aimed to investigate the optimal radiologic method to determine Milan criteria (MC) for the prediction of recurrence in patients who underwent locoregional treatment (LRT) for hepatocellular carcinoma (HCC) and subsequent liver transplantation (LT). METHODS: This retrospective study included 121 HCC patients who underwent LRT and had both liver dynamic CT and MRI. They were classified with MC using four cross combinations of two imaging modalities (CT and MRI) and two diagnostic criteria (modified Response Evaluation Criteria in Solid Tumors [mRECIST] and Liver Imaging Reporting and Data System treatment response algorithm [LI-RADS TRA]). Competing risk regression was performed to analyze the time to recurrence after LT. The predictive abilities of the four methods for recurrence were evaluated using the time-dependent area under the curve (AUC). RESULTS: Competing risk regression analyses found that beyond MC determined by MRI with mRECIST was independently associated with recurrence (hazard ratio, 6.926; p = 0.001). With mRECIST, MRI showed significantly higher AUCs than CT at 3 years and 5 years after LT (0.597 vs. 0.756, p = 0.012 at 3 years; and 0.588 vs. 0.733, p = 0.024 at 5 years). Using the pathologic reference standard, MRI with LI-RADS TRA showed higher sensitivity (61.5%) than CT with LI-RADS TRA (30.8%, p < 0.001) or MRI with mRECIST (38.5%, p < 0.001). CONCLUSIONS: MRI with mRECIST was the optimal radiologic method to determine MC for the prediction of post-LT recurrence in HCC patients with prior LRT. KEY POINTS: • MRI with modified RECIST (mRECIST) is the optimal preoperative method to determine Milan criteria for the prediction of post-transplant HCC recurrence in patients with prior locoregional treatment. • With mRECIST, MRI was better than CT for the prediction of post-transplant recurrence.

Soybean Calmodulin-Binding Transcription Activators, GmCAMTA2 and GmCAMTA8, Coordinate the Circadian Regulation of Developmental Processes and Drought Stress Responses.

The calmodulin-binding transcription activators (CAMTAs) mediate transcriptional regulation of development, growth, and responses to various environmental stresses in plants. To understand the biological roles of soybean CAMTA (GmCAMTA) family members in response to abiotic stresses, we characterized expression patterns of 15 GmCAMTA genes in response to various abiotic stresses. The GmCAMTA genes exhibited distinct circadian regulation expression patterns and were differently expressed in response to salt, drought, and cold stresses. Interestingly, the expression levels of GmCAMTA2, GmCAMTA8, and GmCAMTA12 were higher in stem tissue than in other soybean tissues. To determine the roles of GmCAMTAs in the regulation of developmental processes and stress responses, we isolated GmCAMTA2 and GmCAMTA8 cDNAs from soybean and generated Arabidopsis overexpressing transgenic plants. The GmCAMTA2-OX and GmCAMTA8-OX plants showed hypersensitivity to drought stress. The water in the leaves of GmCAMTA2-OX and GmCAMTA8-OX plants was lost faster than that in wild-type (WT) plants under drought-stress conditions. In addition, stress-responsive genes were down-regulated in the GmCAMTA2-OX and GmCAMTA8-OX plants under drought stress conditions compared to WT plants. Our results suggest that GmCAMTA2 and GmCAMTA8 genes are regulated by circadian rhythms and function as negative regulators in development and drought stress responses.

Retrospective Evaluation of Treatment Response in Patients with Nonmetastatic Pancreatic Cancer Using CT and CA 19-9.

Background Imaging studies have limitations in evaluating pancreatic ductal adenocarcinoma (PDAC) treatment response. Purpose To investigate the effectiveness of combined CT and carbohydrate antigen 19-9 (CA 19-9) evaluation at 8 weeks after first-line treatment to predict overall survival (OS) of patients with nonmetastatic PDAC. Materials and Methods Patients with nonmetastatic PDAC who received first-line treatment with either chemotherapy or concurrent chemoradiation in a single-center PDAC cohort registry were retrospectively enrolled in the study between January 2013 and December 2016. Follow-up CT images obtained 8 weeks after treatment were evaluated according to Response Evaluation Criteria in Solid Tumors. Patients with partial response (PR) or stable disease (SD) were defined as CT responders, and those with progressive disease (PD) were defined as CT nonresponders. Patients with a normalized CA 19-9 level at 8-week follow-up were defined as CA 19-9 responders, and those with a nonnormalized or nonelevated CA 19-9 level were defined as CA 19-9 nonresponders. OS was compared using the Kaplan-Meier method with Breslow analysis. Results A total of 197 patients (mean age ± standard deviation, 65 years ± 10; 107 men) were evaluated. Patients with PD (n = 17) showed shorter OS than those with SD (n = 147; P < .001) or PR (n = 33; P = .003). OS did not differ between the patients with PR and those with SD (P = .60). When the CT and CA 19-9 responses were integrated, OS was longest in CT and CA 19-9 responders (group 1, n = 27; median OS, 26.6 months [95% CI: 9.0, 44.1]), followed by CT responders but CA 19-9 nonresponders (group 2, n = 153; median OS, 15.9 months [95% CI: 13.3, 18.5]; P = .007 vs group 1) and CT and CA 19-9 nonresponders (group 3, n = 17; median OS, 6.5 months [95% CI: 0.8, 12.2]; P < .001 vs group 2). Conclusion Integrated evaluation with CT and carbohydrate antigen 19-9 response allowed more accurate stratification of survival in patients with pancreatic ductal adenocarcinoma in the early treatment period than did evaluation according to Response Evaluation Criteria in Solid Tumors. © 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.

A New Reporting System for Diagnosis of Hepatocellular Carcinoma in Chronic Hepatitis B With Clinical and Gadoxetic Acid-Enhanced MRI Features.

BACKGROUND: Current major guidelines for diagnosis of hepatocellular carcinoma (HCC) based on imaging findings are different from each other and do not include clinical risk factors as a diagnostic criteria. PURPOSE: To developed and validated a new diagnostic score system using MRI and clinical features as applied in chronic hepatitis B patients. STUDY TYPE: Retrospective observational study. SUBJECT: A total of 418 treatment-naïve patients (out of 902 patients) with chronic hepatitis B having 556 lesions suspected for HCC which were eligible for curative treatment. FIELD STRENGTH/SEQUENCE: T1W GRE in- and opposed-phase, T2W FSE, DWI, and T1W 3D-GRE dynamic contrast-enhanced sequences at 1.5  T and 3  T. ASSESSMENT: Six radiologists with 7-22 years of experience independently evaluated MR images based on Liver Imaging Reporting and Data System (LI-RADS) version 2018. STATISTICAL TESTS: Based on logistic regression analysis of MRI features and clinical factors, a risk score system was devised in derivation cohorts (268 patients, 352 lesions) and externally validated (150 patients, 204 lesions). The performance of the new score system was assessed by Harell's c-index. Using cutoff value of 12, maintaining positive predictive value ≥95%, the diagnostic performances of the score system were compared with those of LR-5. RESULTS: The 15-point diagnostic scoring system used MRI features (lesion size, nonrim arterial phase hyperenhancement, portal venous phase hypointensity, hepatobiliary phase hypointensity, and diffusion restriction) and clinical factors (alpha-fetoprotein and platelet). It showed good discrimination in the derivation (c-index, 0.946) and validation cohorts (c-index, 0.907). Using a risk score of 12 as a cut-off, this system yielded higher sensitivity than LR-5 (derivation cohort, 76.8% vs. 52.1%; validation cohort, 73.4% vs. 49.5%) without significant decrease in specificity (derivation cohort, 93.1% vs. 97.2%, P = 0.074; validation cohort, 91.7% vs. 96.1%, P = 0.299). DATA CONCLUSION: A new score system showed improved sensitivity in chronic hepatitis B patients compared to LI-RADS without significant compromise in specificity. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

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.

MRI-diagnosis of category LR-M observations in the Liver Imaging Reporting and Data System v2018: a systematic review and meta-analysis.

OBJECTIVES: We performed a meta-analysis to determine the probability of hepatocellular carcinoma (HCC) and non-HCC malignancies in Liver Imaging Reporting and Data System (LI-RADS) category M (LR-M) observations and the frequency of defined LR-M imaging features on MRI using LI-RADS v2018. METHODS: We searched the MEDLINE and EMBASE databases to identify studies published from 1 January 2018 to 16 March 2021 reporting the probability of category LR-M in HCC and non-HCC malignancies on MRI. The pooled percentages of HCC and non-HCC malignancies in the LR-M observations were evaluated. Meta-regression analysis was performed to identify factors for study heterogeneity. The frequencies of defined LR-M imaging features were also calculated. Risk of bias and concerns regarding applicability were evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. RESULTS: We identified 18 studies reporting the diagnostic performance of the LR-M category (3,812 observations in 3,615 patients), with nine studies reporting the frequencies of LR-M imaging features. The pooled percentages of HCC and non-HCC malignancies in the LR-M observations were 29% (95% confidence interval [CI], 21-38%) and 67% (95%CI, 57-77%), respectively. The study type and inclusion of benign lesions were significant factors for study heterogeneity. Of the 10 LR-M imaging features, rim arterial phase hyperenhancement (APHE) showed the highest frequency in non-HCC malignancies (68%; 95%CI, 61-75%). CONCLUSIONS: The LR-M category was commonly used to characterize non-HCC malignancies, but also included 29% of HCC. The frequencies of the different LR-M imaging features were variable, with rim APHE showing the highest frequency in non-HCC malignancies. KEY POINTS: • In the LR-M category using LI-RADS v2018 for MRI, the pooled percentage of malignancies in general was 96%, with 29% HCC and 67% non-HCC malignancies, while the remaining 4% was benign entity. • The study type and inclusion of benign lesions were significant factors contributing to substantial heterogeneity among included studies. • The frequencies of the different LR-M imaging features were variable, with rim APHE showing the highest frequency in non-HCC malignancies.

Gadoxetic acid-enhanced MRI of macrotrabecular-massive hepatocellular carcinoma and its prognostic implications.

BACKGROUND & AIMS: Despite the clinical and genetic significance of macrotrabecular-massive hepatocellular carcinoma (MTM-HCC), its characteristics on imaging have not been described. This study aimed to characterise MTM-HCC on gadoxetic acid-enhanced MRI and to evaluate the diagnostic accuracy and prognostic value of these imaging characteristics. METHODS: We enrolled 3 independent cohorts from 2 tertiary care centres. The 3 cohorts consisted of a total of 476 patients who underwent gadoxetic acid-enhanced MRI and surgical resection for treatment-naïve single HCCs. Independent review of histopathology and MRI by 2 reviewers was performed for each cohort, and inter-reader agreement was evaluated. Based on the result of MRI review in the training cohort (cohort 1), we developed 2 diagnostic criteria for MTM-HCC and evaluated their prognostic significance. The diagnostic performance and prognostic significance were validated in 2 validation cohorts (cohorts 2 and 3). RESULTS: We developed 2 diagnostic MRI criteria (MRIC) for MTM-HCC: MRIC-1, ≥20% arterial phase hypovascular component; MRIC-2, ≥50% hypovascular component and 2 or more ancillary findings (intratumoural artery, arterial phase peritumoural enhancement, and non-smooth tumour margin). MRIC-1 showed high sensitivity and negative predictive value (88% and 95% in the training cohort, and 88% and 97% in the pooled validation cohorts, respectively), whereas MRIC-2 demonstrated moderate sensitivity and high specificity (47% and 94% in the training cohort, and 46% and 96% in the pooled validation cohorts, respectively). MRIC-2 was an independent poor prognostic factor for overall survival in both training and pooled validation cohorts. CONCLUSIONS: Using gadoxetic acid-enhanced MRI findings, including an arterial phase hypovascular component, we could stratify the probability of MTM-HCC and non-invasively obtain prognostic information. LAY SUMMARY: Macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) is a histopathologic subtype of HCC characterised by aggressive biological behaviour and poor prognosis. We developed imaging criteria based on liver MRI that could be used for the non-invasive diagnosis of MTM-HCC. HCCs showing imaging findings of MTM-HCC were associated with poor outcomes after hepatic resection.

LI-RADS Major Features on MRI for Diagnosing Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: The reported diagnostic performance for hepatocellular carcinoma (HCC) of each major imaging feature on MRI using standardized definitions of the Liver Imaging Reporting and Data System (LI-RADS) is variable. It is important to know the actual performance of each LI-RADS major imaging feature for imaging diagnosis of HCC and determine the sources of heterogeneity between the reported results. PURPOSE: To systematically determine the performance of each major imaging feature of LI-RADS for diagnosing HCC using either extracellular contrast agent-enhanced MRI (ECA-MRI) or gadoxetate disodium-enhanced MRI (EOB-MRI). STUDY TYPE: Systematic review and meta-analysis. SUBJECTS: Sixteen original articles with 3542 lesions. FIELD STRENGTH: A 1.5 T and 3.0 T. ASSESSMENT: Data extraction was independently performed by two reviewers who identified and reviewed original articles reporting the diagnostic performance of each LI-RADS major imaging feature-arterial phase hyperenhancement (APHE), observation size, washout appearance, enhancing "capsule," and threshold growth-using MRI. Study characteristics, study population characteristics, MRI characteristics, contrast agent, LI-RADS version, 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 obtain summary estimates of the diagnostic performance of each LI-RADS major imaging feature. Hierarchical summary receiver operating characteristic curves were plotted. Meta-regression analyses were performed to explore potential sources of heterogeneity. RESULTS: The pooled per-observation sensitivities and specificities for diagnosing HCC were 85% (95% confidence interval [CI] = 78%-89%) and 57% (95% CI = 44%-70%) for arterial phase hyperenhancement (APHE), 77% (95% CI = 72%-82%), and 74% (95% CI = 63%-83%) for washout appearance, and 52% (95% CI = 41%-64%) and 90% (95% CI = 85%-94%) for enhancing "capsule," respectively. DATA CONCLUSIONS: Among the LI-RADS major features, the sensitivity was the highest for APHE and the specificity was the highest for enhancing "capsule" in the diagnosis of HCC. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Characteristics and Early Recurrence of Hepatocellular Carcinomas Categorized as LR-M: Comparison with Those Categorized as LR-4 or 5.

BACKGROUND: According to the Liver Imaging Reporting and Data System (LI-RADS), the LI-RADS category M (LR-M), which are probably or definitely malignant but are not specific for hepatocellular carcinomas (HCCs), does not exclude HCCs. A gap in knowledge remains, including their characteristics and recurrence of HCCs categorized as LR-M. PURPOSE: To compare the characteristics of HCCs categorized as LR-M with HCCs categorized as LR-4 or LR-5 (LR-4/5) using the LI-RADS version 2018 and evaluate the relationship of these categories with the risk of early recurrence after curative resections of single HCCs. STUDY TYPE: Retrospective. SUBJECTS: Two hundred and eighty-one patients (mean age, 57 years; 191 men and 90 women) who underwent curative resections for single HCCs and preoperative contrast-enhanced MRI between 2015 and 2017. FIELD STRENGTH/SEQUENCE: 3T Dual gradient-echo T1 WI with in- and opposed-phase, turbo spin-echo T2 WI, diffusion-weighted echo-planar images, and three-dimensional gradient-echo T1 WI before and after administration of contrast agent. ASSESSMENT: MRI features according to the LI-RADS version 2018 were evaluated and LI-RADS category were assigned for each observation. Clinical, imaging, and histopathological features were compared based on LI-RADS categorization. Early recurrence rates (<2 years) and associated factors were also evaluated. STATISTICAL TESTS: Fisher's exact test, two-sample t test after satisfying assumption of normality through Shapiro-Wilk test, Fleiss κ coefficient, Cox proportional hazards regression analysis, Kaplan-Meier method, and log-rank test. RESULTS: Forty-one HCCs (14.6%) were categorized as LR-M and 240 HCCs (85.4%) were categorized as LR-4/5. LR-M HCCs showed poorer differentiation than LR-4/5 HCCs. In the multivariate analysis, the LR-M category was an independent predictor for early recurrence (hazard ratio, 1.904; 95% confidence interval, 1.024-3.542; P < 0.05). Early recurrence rates were significantly higher in patients with LR-M HCCs than in patients with LR-4/5 HCCs (32.0% vs. 18.4%, respectively, P < 0 05). DATA CONCLUSION: Compared to LR-4/5 HCCs, LR-M HCCs were associated with poorer tumor differentiation and higher early recurrence rates after curative resections of single HCCs. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 2.

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.

Comparison of the current guidelines for diagnosing hepatocellular carcinoma using gadoxetic acid-enhanced magnetic resonance imaging.

OBJECTIVES: To compare the performance of current guidelines applicable to the diagnosis of hepatocellular carcinomas (HCCs) using gadoxetic acid-enhanced magnetic resonance imaging (MRI). METHODS: Two hundred and forty-one hepatic lesions (149 HCCs, six other malignancies, 86 benign lesions) in 177 patients at risk of HCC without a history of previous treatment for hepatic malignancy in a tertiary center were retrospectively reviewed. Either histopathology results or long-term (> 24 months) follow-up images were used as a standard of reference. All lesions were categorized according to the Liver Imaging Reporting and Data System (LI-RADS), European Association for the Study of the Liver (EASL), Asian Pacific Association for the Study of the Liver (APASL), and Korean Liver Cancer Study Group-National Cancer Center (KLCSG-NCC) guidelines. The sensitivity and specificity thereof were assessed using a generalized estimation equation. RESULTS: For gadoxetic acid-enhanced MRI, LI-RADS (95%, 95% confidence interval [CI] 88-98) and EASL (94%, 95% CI 86-97) yielded the highest specificity, while EASL yielded the lowest sensitivity (54% [95% CI 46-62]). APASL yielded the highest sensitivity (91% [95% CI 86-95]) with the lowest specificity (78% [95% CI 69-86]). KLCSG-NCC showed balanced sensitivity (85% [79-90]) and specificity (88% [95% CI 80-93]). Differences were more prominent in small nodules between 1 and 2 cm. CONCLUSION: The diagnostic performance of current guidelines for HCC on gadoxetic acid-enhanced MRI was significantly different, and a potential inverse association between sensitivity and specificity was observed. KEY POINTS: • EASL and LI-RADS yielded the highest specificity with the lowest sensitivity, whereas APASL yielded the highest sensitivity with the lowest specificity. • Differences in the diagnostic performances of guidelines were prominent in small nodules between 1 and 2 cm. • Additional evaluation of CT findings improved the diagnostic sensitivity and accuracy of EASL and LI-RADS. Although doing so decreased specificity, it remained above 89-90%.

Liver MRI with amide proton transfer imaging: feasibility and accuracy for the characterization of focal liver lesions.

OBJECTIVE: To investigate the feasibility of using amide proton transfer (APT) magnetic resonance imaging (MRI) in the liver and to evaluate its ability to characterize focal liver lesions (FLLs). METHODS: A total of 203 patients with suspected FLLs who underwent APT imaging at 3T were included. APT imaging was obtained using a single-slice turbo spin-echo sequence to include FLLs through five breath-holds, and its acquisition time was approximately 1 min. APT signals in the background liver and FLL were measured with magnetization transfer ratio asymmetry (MTRasym) at 3.5 ppm. The technical success rate of APT imaging and the reasons for failure to obtain meaningful MTRasym values were assessed. The Mann Whitney U test was used to compare MTRasym values between different FLLs. RESULTS: The technical success rate of APT imaging in the liver was 62.1% (126/203). The reasons for failure were a too large B0 inhomogeneity (n = 43), significant respiratory motion (n = 12), and these two factors together (n = 22), respectively. Among 59 FLLs with analyzable APT images, MTRasym values were compared between 27 patients with liver metastases and 23 patients with hepatocellular carcinomas (HCCs). The MTRasym values of metastases were significantly higher than those of HCC (0.13 ± 2.15% vs. - 1.41 ± 3.68%, p = 0.027). CONCLUSIONS: APT imaging could be an imaging biomarker for the differentiation of FLLs. However, further technical improvement is required before APT imaging can be clinically applied to liver MRI. KEY POINTS: • Liver APT imaging was technically feasible, but with a relatively low success rate (62.1%). • Liver metastases showed higher APT values than hepatocellular carcinomas.

Extended application of subtraction arterial phase imaging in LI-RADS version 2018: a strategy to improve the diagnostic performance for hepatocellular carcinoma on gadoxetate disodium-enhanced MRI.

OBJECTIVES: This study aimed to assess the detection of hepatocellular carcinoma (HCC) utilizing subtraction AP (arterial phase) imaging only for T1 hyperintense observations compared with the detection of HCC on subtraction AP imaging that included T1 hyper-, iso-, and hypointense lesions on gadoxetate disodium-enhanced MRI. MATERIALS AND METHODS: This retrospective study included 234 patients (311 observations including 239 HCCs) at high risk for HCC who underwent gadoxetate disodium-enhanced MRI with subtraction AP imaging between 2015 and 2017. Arterial phase hyperenhancement (APHE) was divided into two subtypes: conventional APHE, where subtraction AP imaging is used to detect APHE only for T1 hyperintense observations; and modified APHE, where subtraction AP imaging is applied to T1 hyper-, iso-, and hypointense lesions. Two readers independently reviewed all observations and the per-observation diagnostic performances were compared using McNemar's test. RESULTS: Modified nonrim APHE showed significantly higher sensitivity than conventional nonrim APHE (90.0% vs 82.8%; p < 0.001) for diagnosing HCC, without a significant difference in specificity (66.7% vs 68.1%; p > 0.999). The LR-5 category with modified nonrim APHE provided better sensitivity than the LR-5 with conventional nonrim APHE (70.3% vs 63.2%; p < 0.001), without a significant decrease in specificity (94.4% vs 95.8%; p > 0.999). CONCLUSION: Extended application of subtraction AP imaging for T1 hypo- or isointense observations on gadoxetate disodium-enhanced MRI can improve sensitivity in the diagnosis of HCC without a significant difference in specificity. KEY POINTS: • Modified nonrim arterial phase hyperenhancement (APHE), extended application of subtraction arterial phase imaging for T1 hypo- or isointense observation, outperforms conventional nonrim APHE. • The LR-5 category with modified nonrim APHE provided better sensitivity in diagnosing HCC than the LR-5 with conventional APHE, without a significant decrease in specificity.

Subcentimeter hepatocellular carcinoma in treatment-naïve patients: noninvasive diagnostic criteria and tumor staging on gadoxetic acid-enhanced MRI.

OBJECTIVE: It is controversial to adopt non-invasive diagnostic criteria of hepatocellular carcinoma (HCC) in subcentimeter lesions. This study was aimed to define the optimal noninvasive diagnostic criteria of subcentimeter HCC and to evaluate the effect on tumor staging. METHODS: We included 110 treatment-naïve patients at risk of HCC and eligible for curative treatment who had subcentimeter lesions (n = 136) on gadoxetic acid-enhanced magnetic resonance imaging (MRI) performed between January 2013 and December 2013. Modified diagnostic criteria for subcentimeter HCC were developed using logistic regression analysis. Accuracies of MR staging with and without using the modified criteria were compared by generalized estimating equation test using pathologic staging as reference standards. Subgroup analysis was performed for patients with co-existing HCC ≥ 1 cm (co-HCC). RESULTS: The modified criteria (presence of co-HCC, arterial phase hyperenhancement, and hypointensity on transitional phase [TP]) showed 61.5% (95% CI, 41.6-78.2) of sensitivity and 98.2% (95% CI, 93.0-99.5) of specificity. Including subcentimeter HCCs improved the accuracy of MR staging from 84.5 to 94.5% (p = 0.001). Fifty percent of subcentimeter lesions found in patients with co-HCCs were HCC, whereas 5.9% of them without co-HCCs were HCC (p = 0.001). In the subgroup with co-HCCs, the accuracy of MR staging with subcentimeter HCCs was improved from 69.0% to 92.8% (p = 0.001). CONCLUSIONS: Including subcentimeter HCCs based on the modified diagnostic criteria (co-existing HCC ≥ 1 cm, arterial phase hyperenhancement, and hypointensity on TP) improved MR staging accuracy. KEY POINTS: • Fifty percent of non-benign appearing subcentimeter lesions found in patients with co-HCCs were HCC, whereas 5.9% of them without co-HCCs were HCC (p = 0.001). • Including subcentimeter HCCs improved the accuracy of MR staging from 84.5 to 94.5% (p = 0.001).

Noninvasive evaluation of liver fibrosis: comparison of the stretched exponential diffusion-weighted model to other diffusion-weighted MRI models and transient elastography.

OBJECTIVES: To compare the diagnostic performance of the stretched exponential model to those of other DWI models and transient elastography (TE) and to evaluate the influence of confounding factors on the staging of liver fibrosis. METHODS: This retrospective study included 78 consecutive patients who underwent both DWI and TE. The distributed diffusion coefficient (DDC) and intravoxel heterogeneity index (α) from the stretched exponential model, apparent diffusion coefficient (ADC), perfusion fraction (f), pseudodiffusion coefficient (Dp), true diffusion coefficient (Dt), and TE were obtained. Associations between imaging parameters and pathological fibrosis, inflammation, and steatosis were evaluated using Spearman's correlation and multiple regression analysis. Diagnostic accuracy of parameters for fibrosis staging was assessed via the Obuchowski measures. RESULTS: DDC was the only parameter to differ between F0-1 and F2-3 (p < 0.001) and between F2-3 and F4 (p = 0.013). DDC showed significant correlation with fibrosis (p < 0.001) and inflammation (p = 0.001), but not with steatosis (p = 0.619), and was independently associated with only fibrosis in multiple regression analysis (ß = - 0.114, p < 0.001). ADC, Dp, and Dt showed a significant correlation with steatosis (ps ≤ 0.038). DDC showed the highest diagnostic performance for liver fibrosis (0.717; 95% confidence interval, 0.653-0.765) followed by TE (0.681, 0.623-0.733) without a significant difference between DDC and TE (p > 0.999). CONCLUSIONS: DDC from the stretched exponential model is the most accurate DWI parameter with no confounding effect from steatosis and with overall similar diagnostic performance to TE. KEY POINTS: • The distributed diffusion coefficient (DDC) from the stretched exponential model is the most accurate DWI parameter for staging liver fibrosis. • DDC and transient elastography have similar good diagnostic performance for evaluating liver fibrosis. • The stretched exponential DWI model has no confounding effect by steatosis, unlike other DWI models.