Comparison of the different versions of NCCN guidelines for predicting margin-negative resection of pancreatic cancer in patients undergoing upfront surgery.

OBJECTIVES: The purpose of this study was to compare the different versions of the National Comprehensive Cancer Network (NCCN) guidelines for defining resectability of pancreatic ductal adenocarcinoma (PDAC) in predicting margin-negative (R0) resection, and to assess inter-reader agreement. METHODS: This retrospective study included 283 patients (mean age, 65.1 years ± 9.4 [SD]; 155 men) who underwent upfront pancreatectomy for PDAC between 2017 and 2019. Two radiologists independently determined the resectability on preoperative CT according to the 2017, 2019, and 2020 NCCN guidelines. The sensitivity and specificity for R0 resection were analyzed using a multivariable logistic regression analysis with generalized estimating equations. Inter-reader agreement was assessed using kappa statistics. RESULTS: R0 resection was accomplished in 239 patients (84.5%). The sensitivity and specificity averaged across two readers were, respectively, 76.6% and 29.5% for the 2020 guidelines, 74.1% and 32.9% for the 2019 guidelines, and 72.6% and 34.1% for the 2017 guidelines. Compared with the 2020 guidelines, both 2019 and 2017 guidelines showed significantly lower sensitivity for R0 resection (p ≤ .009). Specificity was significantly higher with the 2017 guidelines (p = .043) than with the 2020 guidelines. Inter-reader agreements for determining the resectability of PDCA were strong (k ≥ 0.83) with all guidelines, being highest with the 2020 guidelines (k = 0.91). CONCLUSION: The 2020 NCCN guidelines showed significantly higher sensitivity for prediction of R0 resection than the 2017 and 2019 guidelines.

Ultrasound-based steatosis grading system using 2D-attenuation imaging: An individual patient data meta-analysis with external validation.

BACKGROUND AND AIMS: Noninvasive tools assessing steatosis, such as ultrasonography-based 2D-attenuation imaging (ATI), are needed to tackle the worldwide burden of steatotic liver disease. This one-stage individual patient data (IPD) meta-analysis aimed to create an ATI-based steatosis grading system. APPROACH AND RESULTS: A systematic review (EMBASE + MEDLINE, 2018-2022) identified studies, including patients with histologically or magnetic resonance imaging proton-density fat fraction (MRI-PDFF)-verified ATI for grading steatosis (S0 to S3). One-stage IPD meta-analyses were conducted using generalized mixed models with a random study-specific intercept. Created ATI-based steatosis grading system (aS0 to aS3) was externally validated on a prospective cohort of patients with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (n=174, histologically and MRI-PDFF-verified steatosis). Eleven enrolled studies included 1374 patients, classified into S0, S1, S2, and S3 in 45.4%, 35.0%, 9.3%, and 10.3% of the cases. ATI was correlated with histological steatosis ( r = 0.60; 95% CI: 0.52, 0.67; p < 0.001) and MRI-PDFF ( r = 0.70; 95% CI: 0.66, 0.73; p < 0.001) but not with liver stiffness ( r = 0.03; 95% CI: -0.04, 0.11, p = 0.343). Steatosis grade was an independent factor associated with ATI (coefficient: 0.24; 95% CI: [0.22, 0.26]; p < 0.001). ATI marginal means within S0, S1, S2, and S3 subpopulations were 0.59 (95% CI: [0.58, 0.61]), 0.69 (95% CI [0.67, 0.71]), 0.78 (95% CI: [0.76, 0.81]), and 0.85 (95% CI: [0.83, 0.88]) dB/cm/MHz; all contrasts between grades were significant ( p < 0.0001). Three ATI thresholds were calibrated to create a new ATI-based steatosis grading system (aS0 to aS3, cutoffs: 0.66, 0.73, and 0.81 dB/cm/MHz). Its external validation showed Obuchowski measures of 0.84 ± 0.02 and 0.82 ± 0.02 with histologically based and MRI-PDFF-based references. CONCLUSIONS: ATI is a reliable, noninvasive marker of steatosis. This validated ATI-based steatosis grading system could be valuable in assessing patients with metabolic dysfunction-associated steatotic liver disease.

Interpretation of Complete Tumor Response on MRI Following Chemoradiotherapy of Rectal Cancer: Inter-Reader Agreement and Associated Factors in Multi-Center Clinical Practice.

OBJECTIVE: To measure inter-reader agreement and identify associated factors in interpreting complete response (CR) on magnetic resonance imaging (MRI) following chemoradiotherapy (CRT) for rectal cancer. MATERIALS AND METHODS: This retrospective study involved 10 readers from seven hospitals with experience of 80-10210 cases, and 149 patients who underwent surgery after CRT for rectal cancer. Using MRI-based tumor regression grading (mrTRG) and methods employed in daily practice, the readers independently assessed mrTRG, CR on T2-weighted images (T2WI) denoted as mrCRT2W, and CR on all images including diffusion-weighted images (DWI) denoted as mrCRoverall. The readers described their interpretation patterns and how they utilized DWI. Inter-reader agreement was measured using multi-rater kappa, and associated factors were analyzed using multivariable regression. Correlation between sensitivity and specificity of each reader was analyzed using Spearman coefficient. RESULTS: The mrCRT2W and mrCRoverall rates varied widely among the readers, ranging 18.8%-40.3% and 18.1%-34.9%, respectively. Nine readers used DWI as a supplement sequence, which modified interpretations on T2WI in 2.7% of cases (36/1341 [149 patients × 9 readers]) and mostly (33/36) changed mrCRT2W to non-mrCRoverall. The kappa values for mrTRG, mrCRT2W, and mrCRoverall were 0.56 (95% confidence interval: 0.49, 0.62), 0.55 (0.52, 0.57), and 0.54 (0.51, 0.57), respectively. No use of rectal gel, larger initial tumor size, and higher initial cT stage exhibited significant association with a higher inter-reader agreement for assessing mrCRoverall (P ≤ 0.042). Strong negative correlations were observed between the sensitivity and specificity of individual readers (coefficient, -0.718 to -0.963; P ≤ 0.019). CONCLUSION: Inter-reader agreement was moderate for assessing CR on post-CRT MRI. Readers' varying standards on MRI interpretation (i.e., threshold effect), along with the use of rectal gel, initial tumor size, and initial cT stage, were significant factors associated with inter-reader agreement.

Value of Doppler ultrasonography in predicting clinical outcomes for patients with acute cellular rejection after liver transplantation.

PURPOSE: This study investigated the value of Doppler ultrasonography in predicting clinical outcomes after antirejection treatment for patients with acute cellular rejection (ACR) following liver transplantation (LT). METHODS: This retrospective study included 84 patients who were pathologically diagnosed with ACR and received antirejection treatment within 90 days following LT. Two radiologists searched for abnormal Doppler parameters at ACR diagnosis and within 7 days after antirejection treatment initiation, including portal blood velocity (PBV) <20 cm/s, hepatic artery resistive index <0.5, and a monophasic hepatic vein flow pattern. Interval PBV changes were also evaluated. The frequencies of abnormal Doppler parameters and PBV changes were compared by treatment outcome. RESULTS: The frequency of abnormal PBV in the early post-treatment phase (PBVearly post-treatment) was significantly higher among poor responders (50.0% [10/20]) than among good responders (7.8% [5/64]) (P<0.001). The sensitivity, specificity, and accuracy of abnormal PBVearly post-treatment as a predictor of poor response to antirejection treatment were 50.0% (10/20), 92.2% (59/64), and 82.1% (69/84), respectively. A decrease (>10%) from the PBV at event (PBVevent) to PBVearly post-treatment was significantly more common among poor responders (50.0% [10/20]) than among good responders (20.3% [13/64]) (P=0.019). The sensitivity, specificity, and accuracy of this PBV decrease in predicting poor treatment response were 50.0% (10/20), 79.7% (51/64), and 72.6% (61/84), respectively. CONCLUSION: Abnormal PBVearly post-treatment and a decrease between PBVevent and PBVearly post-treatment were significantly associated with poor treatment response in patients with ACR after LT. Consequently, Doppler ultrasonography may be useful for predicting clinical outcomes in these patients.

Transient elastography with controlled attenuation parameter versus two-dimensional shear wave elastography with attenuation imaging for the evaluation of hepatic steatosis and fibrosis in NAFLD.

PURPOSE: This study compared the controlled attenuation parameter (CAP) to attenuation imaging (ATI) in the diagnosis of steatosis and transient elastography (TE) to two-dimensional shear wave elastography (2D-SWE) for the diagnosis of fibrosis in a prospectively constructed nonalcoholic fatty liver disease (NAFLD) patient cohort. METHODS: Participants who underwent TE with CAP were included from a previously constructed NAFLD cohort with multiparametric ultrasound data. The degree of hepatic steatosis and stage of liver fibrosis were assessed. Diagnostic performance was evaluated using the area under the receiver operating characteristic curve (AUROC) for the grades of steatosis (S1-3) and fibrosis (F0-F4). RESULTS: There were 105 participants. The distribution of hepatic steatosis grades (S0-S3) and liver fibrosis stages (F0-F4) was as follows: S0, n=34; S1, n=41; S2, n=22; S3, n=8; F0, n=63; F1, n=25; F2, n=5; F3, n=7; and F4, n=5. No significant difference was found between CAP and ATI in detecting ≥S1 (AUROC: 0.93 vs. 0.93, P=0.956) or ≥S2 (0.94 vs. 0.94, P=0.769). However, the AUROC of ATI in detecting ≥S3 was significantly higher than that of CAP (0.94 vs. 0.87, P=0.047). Regarding the detection of liver fibrosis, no significant difference was found between TE and 2D-SWE. The AUROCs of TE and 2D-SWE were as follows: ≥F1, 0.94 vs. 0.89 (P=0.107); ≥F2, 0.89 vs. 0.90 (P=0.644); ≥F3, 0.91 vs. 0.90 (P=0.703); and ≥F4, 0.88 vs. 0.92 (P=0.209). CONCLUSION: 2D-SWE and TE showed comparable diagnostic performance in assessing liver fibrosis, and ATI provided significantly better performance in detecting ≥S3 steatosis than CAP.

Pathologic Implications of Magnetic Resonance Imaging-detected Extramural Venous Invasion of Rectal Cancer.

BACKGROUND: Extramural venous invasion (EMVI) is a poor prognostic factor in rectal cancer. Recent advances in magnetic resonance imaging (MRI) allow for the detection of EMVI before surgery. This study aimed to analyze the correlations between MRI-detected EMVI (MR-EMVI) and pathologic parameters in patients with rectal cancer. MATERIALS AND METHODS: This study retrospectively analyzed 721 patients who underwent radical resection for locally advanced rectal cancer between 2018 and 2019 at the Asan Medical center. All patients underwent an MRI before surgery. The lesions of patients who received neoadjuvant chemoradiation therapy (CRT) were evaluated by MRI before and after the neoadjuvant CRT. RESULTS: Of the 721 patients, 118 (16.4%) showed a positive MR-EMVI, which significantly correlated with advanced pathologic T-category and N-category, extranodal extension, poor differentiation, lymphatic invasion, venous invasion, and perineural invasion. In addition, MR-EMVI was an independent factor for predicting the pathologic nodal status (OR 3.476, 95% CI, 2.186-5.527, P < .001). Patients with a positive MR-EMVI had a sensitivity of 28.0% and specificity of 91.9% for predicting regional lymph node metastasis, whereas the MR-N category had a sensitivity of 88.7% and specificity of 30.6%. Patients whose MR-EMVI changed from positive to negative after neoadjuvant CRT had no significant differences in pathologic parameters except for lymphatic invasion with patients who were negative before and after neoadjuvant CRT. CONCLUSION: MR-EMVI correlated with aggressive pathologic features, which indicated a poor prognosis. MR-EMVI may be a complementary imaging biomarker for predicting nodal status and evaluating tumor response to neoadjuvant CRT.

Deep learning-based imaging reconstruction for MRI after neoadjuvant chemoradiotherapy for rectal cancer: effects on image quality and assessment of treatment response.

PURPOSE: To investigate the effects of deep learning-based imaging reconstruction (DLR) on the image quality of MRI of rectal cancer after chemoradiotherapy (CRT), and its accuracy in diagnosing pathological complete responses (pCR). METHODS: We included 39 patients (men: women, 21:18; mean age ± standard deviation, 59.1 ± 9.7 years) with mid-to-lower rectal cancer who underwent a long-course of CRT and high-resolution rectal MRIs between January 2020 and April 2021. Axial T2WI was reconstructed using the conventional method (MRIconv) and DLR with two different noise reduction factors (MRIDLR30 and MRIDLR50). The signal-to-noise ratio (SNR) of the tumor was measured. Two experienced radiologists independently made a blind assessment of the complete response on MRI. The sensitivity and specificity for pCR were analyzed using a multivariable logistic regression analysis with generalized estimating equations. RESULTS: Thirty-four patients did not have a pCR whereas five (12.8%) had pCR. Compared with the SNR of MRIconv (mean ± SD, 7.94 ± 1.92), MRIDLR30 and MRIDLR50 showed higher SNR (9.44 ± 2.31 and 11.83 ± 3.07, respectively) (p < 0.001). Compared to MRIconv, MRIDLR30 and MRIDLR50 showed significantly higher specificity values (p < 0.036) while the sensitivity values were not significantly different (p > 0.301). The sensitivity and specificity for pCR were 48.9% and 80.8% for MRIconv; 48.9% and 88.2% for MRIDLR30; and 38.8% and 86.7% for MRIDLR50, respectively. CONCLUSION: DLR produced MR images with higher resolution and SNR. The specificity of MRI for identification of pCR was significantly higher with DLR than with conventional MRI.

Cutoff Values for Diagnosing Hepatic Steatosis Using Contemporary MRI-Proton Density Fat Fraction Measuring Methods.

OBJECTIVE: To propose standardized MRI-proton density fat fraction (PDFF) cutoff values for diagnosing hepatic steatosis, evaluated using contemporary PDFF measuring methods in a large population of healthy adults, using histologic fat fraction (HFF) as the reference standard. MATERIALS AND METHODS: A retrospective search of electronic medical records between 2015 and 2018 identified 1063 adult donor candidates for liver transplantation who had undergone liver MRI and liver biopsy within a 7-day interval. Patients with a history of liver disease or significant alcohol consumption were excluded. Chemical shift imaging-based MRI (CS-MRI) PDFF and high-speed T2-corrected multi-echo MR spectroscopy (HISTO-MRS) PDFF data were obtained. By temporal splitting, the total population was divided into development and validation sets. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance of the MRI-PDFF method. Two cutoff values with sensitivity > 90% and specificity > 90% were selected to rule-out and rule-in, respectively, hepatic steatosis with reference to HFF ≥ 5% in the development set. The diagnostic performance was assessed using the validation set. RESULTS: Of 921 final participants (624 male; mean age ± standard deviation, 31.5 ± 9.0 years), the development and validation sets comprised 497 and 424 patients, respectively. In the development set, the areas under the ROC curve for diagnosing hepatic steatosis were 0.920 for CS-MRI-PDFF and 0.915 for HISTO-MRS-PDFF. For ruling-out hepatic steatosis, the CS-MRI-PDFF cutoff was 2.3% (sensitivity, 92.4%; specificity, 63.0%) and the HISTO-MRI-PDFF cutoff was 2.6% (sensitivity, 88.8%; specificity, 70.1%). For ruling-in hepatic steatosis, the CS-MRI-PDFF cutoff was 3.5% (sensitivity, 73.5%; specificity, 88.6%) and the HISTO-MRI-PDFF cutoff was 4.0% (sensitivity, 74.7%; specificity, 90.6%). CONCLUSION: In a large population of healthy adults, our study suggests diagnostic thresholds for ruling-out and ruling-in hepatic steatosis defined as HFF ≥ 5% by contemporary PDFF measurement methods.

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.

Progression of Portal Hypertension in Acute Cellular Rejection After Liver Transplantation.

OBJECTIVES: This study was designed to investigate the frequency of computed tomography features indicating progression of portal hypertension and their clinical relevance in patients who experienced acute cellular rejection after liver transplantation. MATERIALS AND METHODS: This retrospective study included 141 patients with pathologically diagnosed acute cellular rejection following liver transplant. Patients were divided into early and late rejection groups according to the time of diagnosis. Two radiologists analyzed the interval changes in spleen size and variceal engorgement on computed tomography images obtained at the times of surgery and biopsy. Aggravation of splenomegaly and variceal engorgement were considered computed tomography features associated with the progression of portal hypertension. Clinical outcomes, including responses to treatment and graft survival, were compared between patients with and without these features. RESULTS: The frequency of progression of portal hypertension was 31.9% and did not differ significantly in patients who experienced early (30.8% [28/91]) and late (34.0% [17/50]) rejection (P = .694). In the late rejection group, computed tomography features indicating progression of portal hypertension were significantly associated with poor response to treatment (P = .033). Graft survival in both the early and late rejection groups did not differ significantly in patients with and without progression of portal hypertension. CONCLUSIONS: Computed tomography features suggesting the progression of portal hypertension were encountered in about one-third of patients who experienced acute cellular rejection after liver transplant. Progression of portal hypertension was significantly related to poor response to treatment in the late rejection group.

Safety and Efficacy of Chimeric Antigen Receptor T-Cell Therapy for Glioblastoma: A Systemic Review and Meta-Analysis.

Background: Chimeric antigen receptor (CAR) T-cell therapy is a promising treatment option for patients with refractory hematological malignancies. However, its efficacy in glioblastoma remains unclear. Here, we performed a systematic review to summarize the safety and efficacy of CAR T-cell therapy in glioblastoma. Methods: The PubMed, EMBASE, and Cochrane databases were searched to identify articles published before June 30, 2021 describing the use of CAR T-cell therapy in glioblastoma. Information on the toxicity of CAR T-cell therapy was summarized. The pooled objective response rate (ORR) and overall survival (OS) of patients who underwent CAR T-cell therapy were estimated using a random-effects model with an inverse-variance weighting model and quantile estimation method, respectively. Results: Of 397 articles identified, eight studies including 63 patients with recurrent glioblastoma treated with various CAR T-cell regimens were included in the analysis. Six (9.5%) patients developed cytokine release syndrome (grade ≤2), and 16 (25.4%) experienced non-critical neurological events. The pooled ORR was 5.1% (95% confidence interval [CI], 0.0-10.4; I 2 = 0.05%), and the pooled median OS was 8.1 months (95% CI, 6.7-9.5; I 2 = 0.00%). Conclusion: Although CAR T-cell therapy is a relatively safe therapeutic option in patients with glioblastoma, it shows marginal efficacy, suggesting that further research is necessary for its translation into clinical practice for the treatment of recurrent glioblastoma.

Two-dimensional Shear-Wave Elastography and US Attenuation Imaging for Nonalcoholic Steatohepatitis Diagnosis: A Cross-sectional, Multicenter Study.

Background Multiparametric US examination may have potential in the comprehensive evaluation of nonalcoholic fatty liver disease (NAFLD), but multicenter studies are lacking. Purpose To evaluate the diagnostic performance of multiparametric US with the attenuation coefficient (AC) from attenuation imaging (ATI) and liver stiffness (LS) and dispersion slope (DS) from two-dimensional (2D) shear-wave elastography (SWE) in a multicenter study of patients with NAFLD. Materials and Methods This prospective study enrolled consecutive participants between December 2019 and June 2021 with suspected nonalcoholic steatohepatitis (NASH) who were scheduled to undergo liver biopsy in five tertiary hospitals. Before the procedure, all participants underwent US with ATI and 2D SWE according to the study protocol. Multivariable linear regression analyses were performed to determine the significant determinant factors for AC, LS, and DS. Diagnostic performance was decided based on the areas under the receiver operating characteristic curve (AUCs). Results A total of 132 participants (median age, 38 years; IQR, 27-54 years; 69 women) were evaluated. Among the participant characteristics, including pathologic findings, demographic characteristics, body mass index, and serum markers, hepatic steatosis for AC (P < .001), lobular inflammatory activity for DS (P = .007), and both fibrosis (P = .01) and lobular inflammatory activity (P = .04) for LS were significant determinant factors. At histopathologic examination, 53 of the 132 participants (40.2%) had NASH. The risk score system obtained using unweighted sum of scores from AC and DS showed the best diagnostic performance in the detection of NASH (AUC = 0.94; 95% CI: 0.89, 0.98; P < .05 for all), as compared with serum markers or other US parameters alone (AUC ≤ 0.88). Conclusion US attenuation imaging and two-dimensional shear-wave elastography were useful for assessing hepatic steatosis, lobular inflammation, and fibrosis. The risk score system obtained using the attenuation coefficient and dispersion slope showed the best diagnostic performance fo r nonalcoholic steatohepatitis. cris.nih.go.kr no. KCT0004326 © RSNA, 2022 Online supplemental material is available for this article.

Prediction of margin-negative resection of pancreatic ductal adenocarcinoma following neoadjuvant therapy: Diagnostic performance of NCCN criteria for resection vs CT-determined resectability.

BACKGROUND: Accurate assessment of pancreatic ductal adenocarcinoma (PDAC) resectability after neoadjuvant therapy (NAT) is crucial. Recently, the NCCN introduced criteria for resection of PDAC following NAT. METHODS: We analyzed 127 patients who underwent NAT and pancreatectomy for PDAC between January 2010 and March 2020. CT-determined resectability according to the NCCN guideline and CA 19-9 level was evaluated before and after NAT. Diagnostic performance of the NCCN criteria for margin-negative (R0) resection was investigated and compared with CT alone. RESULTS: R0 resection was achieved in 104 (81.9%) patients. After NAT, there were 30 (23.6%) resectable, 90 (70.9%) borderline resectable, and seven (5.5%) locally advanced tumors. Significantly decreased or stable CA 19-9 levels were noted in 114 (89.8%) patients. The sensitivity and specificity of the NCCN criteria were 87.5% (91/104) and 21.7% (5/23), respectively, which were significantly different from CT including only resectable PDAC (26.9% [28/104] and 91.3% [21/23]; P < .001), but less prominently different from CT including resectable and borderline resectable PDAC (95.2% [99/104]; P = .022 and 8.7% [2/23]; P = .375). CONCLUSIONS: The NCCN criteria for resection following NAT showed high sensitivity and low specificity for predicting R0 resection. It had supplementary benefit over CT alone, mainly in preventing underestimation of R0 resection.

New strategy for Liver Imaging Reporting and Data System category M to improve diagnostic performance of MRI for hepatocellular carcinoma ≤ 3.0 cm.

PURPOSE: We aimed to determine a new strategy for Liver Imaging Reporting and Data System category M (LR-M) criteria to improve the diagnosis of HCC ≤ 3.0 cm on magnetic resonance imaging (MRI). METHODS: A total of 463 pathologically confirmed hepatic observations ≤ 3.0 cm (375 HCCs, 32 other malignancies, 56 benignities) in 384 patients at risk of HCC who underwent gadoxetate-enhanced MRI were retrospectively analyzed. Two radiologists evaluated the presence of major, ancillary, and LR-M features according to LI-RADS v2018. Of the ten LR-M features, those significantly associated with non-HCC malignancy were identified using multivariable logistic regression analysis, and new LR-M criteria for improving the diagnosis of HCC were investigated. Generalized estimating equations were used to compare sensitivity and specificity of LR-5 for diagnosing HCC using the new LR-M criteria with values calculated using the original LR-M criteria. p < 0.05 was considered to indicate a significant difference. RESULTS: Of ten LR-M features, rim arterial-phase hyperenhancement, delayed central enhancement, targetoid restriction, and targetoid transitional-phase/hepatobiliary-phase appearance were independently significantly associated with non-HCC malignancy (adjusted odds ratio ≥ 6.2; p ≤ 0.02). Using the new LR-M criteria (two or more of these significant features), the sensitivity of LR-5 for diagnosing HCC was higher than that with the original LR-M criteria (69% [95% confidence interval 64-73%] vs. 65% [61-70%], p = 0.002), whereas the specificity was similar (90% [82-95%] vs. 92% [83-96%], p = 0.28). CONCLUSION: The new LR-M criteria (two or more significant features) can improve the sensitivity of LR-5 for diagnosing HCC ≤ 3.0 cm, without compromising specificity.

Impact of the Liver Imaging Reporting and Data System on Research Studies of Diagnosing Hepatocellular Carcinoma Using MRI.

OBJECTIVE: Since its introduction in 2011, the CT/MRI diagnostic Liver Imaging Reporting and Data System (LI-RADS) has been updated in 2014, 2017, and 2018. We evaluated the impact of CT/MRI diagnostic LI-RADS on liver MRI research methodology for the diagnosis of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The MEDLINE, EMBASE, and Cochrane databases were searched for original articles reporting the diagnostic performance of liver MRI for HCC between 2011 and 2019. The MRI techniques, image analysis methods, and diagnostic criteria for HCC used in each study were investigated. The studies were classified into three groups according to the year of publication (2011-2013, 2014-2016, and 2017-2019). We compared the percentage of studies adopting MRI techniques recommended by LI-RADS, image analysis methods in accordance with the lexicon defined in LI-RADS, and diagnostic criteria endorsed by LI-RADS. We compared the pooled sensitivity and specificity between studies that used the LI-RADS and those that did not. RESULTS: This systematic review included 179 studies. The percentages of studies using imaging techniques recommended by LI-RADS were 77.8% for 2011-2013, 85.7% for 2014-2016, and 84.2% for 2017-2019, with no significant difference (p = 0.951). After the introduction of LI-RADS, the percentages of studies following the LI-RADS lexicon were 0.0%, 18.4%, and 56.6% in the respective periods (p < 0.001), while the percentages of studies using the LI-RADS diagnostic imaging criteria were 0.0%, 22.9%, and 60.7%, respectively (p < 0.001). Studies that did not use the LI-RADS and those that used the LI-RADS version 2018 showed no significant difference in sensitivity and specificity (86.3% vs. 77.7%, p = 0.102 and 91.4% vs. 89.9%, p = 0.770, respectively), with some difference in heterogeneity (I² = 94.3% vs. 86.7% in sensitivity and I² = 86.6% vs. 53.2% in specificity). CONCLUSION: LI-RADS imparted significant changes in the image analysis methods and diagnostic criteria used in liver MRI research for the diagnosis of HCC.

Diagnostic value of [68 Ga]Ga-DOTA-labeled-somatostatin analogue PET/MRI for detecting liver metastasis in patients with neuroendocrine tumors: a systematic review and meta-analysis.

OBJECTIVES: To determine the diagnostic value of [68 Ga]Ga-DOTA-labeled-somatostatin analogue ([68 Ga]Ga-DOTA-SSA) PET/MRI for detecting liver metastasis in patients with neuroendocrine tumor (NET) and to compare it with [68 Ga]Ga-DOTA-SSA PET/CT. METHODS: A search of MEDLINE, EMBASE, and Cochrane was performed to identify original articles reporting the detection rate of [68 Ga]Ga-DOTA-SSA PET/MRI for liver metastasis in comparison with PET/CT. The pooled detection rates for liver metastasis on PET/MRI and PET/CT were calculated and compared using a restricted maximum likelihood estimation of random-effects model. The pooled added value of PET/MRI in comparison with PET/CT was calculated. Sensitivity analysis and subgroup analysis were performed to explore causes of study heterogeneity. RESULTS: In the six included studies (638 liver metastases), the pooled detection rates for liver metastasis on [68 Ga]Ga-DOTA-SSA PET/MRI and PET/CT were 93.5% (95% confidence interval [CI], 85.1-97.3%; I2 = 84.8%) and 76.8% (95% CI, 64.8-85.6%; I2 = 87.8%), respectively. PET/MRI had a significantly higher detection rate than PET/CT (p = 0.02), with 15.3% (95% CI, 8.0-27.4%) added value over PET/CT. After sensitivity analysis, the recalculated detection rates for liver metastasis were 94.8% (95% CI, 90.8-97.2%; I2 = 42.1%) for PET/MRI and 80.0% (95% CI, 65.3-89.5%; I2 = 90.0%) for PET/CT. The study location and the use of predefined imaging criteria for liver metastasis were associated with PET/MRI study heterogeneity. CONCLUSION: [68 Ga]Ga-DOTA-SSA PET/MRI had good overall performance for detecting liver metastasis in patients with NET. Because of the small number of eligible studies, further studies are needed to validate the clinical usefulness of [68 Ga]Ga-DOTA-SSA PET/MRI. KEY POINTS: • [68 Ga]Ga-DOTA-SSA PET/MRI had a higher pooled detection rate for liver metastasis than PET/CT (93.5% vs. 76.8%). • The added value of [68 Ga]Ga-DOTA-SSA PET/MRI for detecting liver metastasis in comparison with PET/CT was 15.3%. •Study location and the predefined imaging criteria for liver metastasis were significant factors causing PET/MRI study heterogeneity.

Diagnostic performance of liver fibrosis assessment by quantification of liver surface nodularity on computed tomography and magnetic resonance imaging: systematic review and meta-analysis.

OBJECTIVES: To determine the diagnostic performance of the liver surface nodularity (LSN) score for assessment of hepatic fibrosis. METHODS: Major databases were searched to identify studies reporting the diagnostic performance of the LSN score published from January 2011 to April 2021. The pooled sensitivity and specificity of the LSN score in the diagnosis of significant fibrosis (F2-4), advanced fibrosis (F3-4), and liver cirrhosis (F4) were calculated using a bivariate random-effects model, and the summary areas under the hierarchical summary receiver operating characteristics curve (AUC) for each were calculated. Subgroup analysis was performed to explore the causes of study heterogeneity. RESULTS: Of 168 screened studies, six were included in the analysis. The pooled sensitivity, specificity, and AUC of the LSN score were 68% (95% confidence interval [CI], 45-84%), 89% (95% CI, 83-93%), and 0.90 (95% CI, 0.87-0.92), respectively, for the diagnosis of significant fibrosis; 88% (95% CI, 60-97%), 78% (95% CI, 57-90%), and 0.89 (95% CI, 0.86-0.91), respectively, for the diagnosis of advanced fibrosis; and 83% (95% CI, 71-91%), 80% (95% CI, 72-85%), and 0.87 (95% CI, 0.83-0.89), respectively, for the diagnosis of liver cirrhosis. Cutoff values of the LSN score affected study heterogeneity in the diagnosis of advanced fibrosis (p = 0.03) and liver cirrhosis (p = 0.01). Imaging modality (p = 0.01) and reference standard (p = 0.01) affected study heterogeneity in the diagnosis of liver cirrhosis. CONCLUSIONS: The LSN score showed good diagnostic performance in assessing the hepatic fibrosis stage. Additional investigations are needed to improve and standardize the LSN score. Key Points • The liver surface nodularity (LSN) score showed overall good diagnostic performance in assessing hepatic fibrosis. • The pooled sensitivity of the LSN score was highest in the diagnosis of advanced fibrosis (88%; 95% confidence interval [CI], 60-97%), and the pooled specificity was highest in the diagnosis of significant fibrosis (89%; 95% CI, 83-93%). • The diagnostic performance of the LSN score differed according to the cutoff value, imaging modality, and reference standard.

Accuracy of the ultrasound attenuation coefficient for the evaluation of hepatic steatosis: a systematic review and meta-analysis of prospective studies.

PURPOSE: The accurate detection and quantification of hepatic steatosis using a noninvasive method are important for the management of nonalcoholic fatty liver disease. We performed a systematic review and meta-analysis of the accuracy of the ultrasound-measured attenuation coefficient (AC) in the evaluation of hepatic steatosis. METHODS: The PubMed, Embase, and Cochrane databases were searched for prospective studies reporting the diagnostic accuracy of AC for assessing hepatic steatosis. The meta-analytic pooled sensitivity and specificity of AC for any grade of steatosis (S≥1) and advanced steatosis (S≥2) were estimated using a bivariate random-effects model. Meta-regression analysis was conducted to investigate the causes of heterogeneity among studies. RESULTS: Thirteen studies including 1,509 patients were identified. The pooled sensitivity and specificity of AC for S≥1 were 76% (95% confidence interval [CI], 73% to 80%; I2=43%) and 84% (95% CI, 77% to 89%; I2=74%), respectively, while for S≥2 they were 87% (95% CI, 83% to 91%; I2=0%) and 79% (95% CI, 75% to 83%; I2=59%), respectively. Study heterogeneity was associated with body mass index (BMI) and the prevalence of steatosis or significant fibrosis. CONCLUSION: AC can be clinically useful for assessing hepatic steatosis, with good overall diagnostic performance. The data reported in the published literature differed according to BMI and the prevalence of steatosis or significant fibrosis, and careful interpretation with consideration of these factors might be needed.

Diagnostic performance of ultrasound attenuation imaging for assessing low-grade hepatic steatosis.

OBJECTIVES: To investigate the diagnostic performance of attenuation imaging (ATI) for the assessment of low-grade hepatic steatosis using liver biopsy as the reference standard. METHODS: The study included 57 potential donor candidates for living liver transplantation who underwent ATI, transient elastography (TE), and liver biopsy for evaluation of hepatic steatosis between February 2020 and April 2020. The attenuation coefficient (AC) from ATI and the controlled attenuation parameter (CAP) from TE were measured for each participant in a random and blind manner. The histologic hepatic fat fraction (HFF) was graded (S0, < 5%; S1, 5-33%; S2, 33-66%; S3, > 66%). The accuracy of ATI for diagnosing hepatic steatosis was compared with that of CAP using ROC analysis. Correlations between AC and HFF were evaluated, and factors affecting AC were determined by linear regression analysis. RESULTS: The median HFF was 3% (range: 0-35%), with 31 (54.4%), 24 (42.0%), and 2 (3.5%) participants being graded as S0, S1, and S2, respectively. The AUCs for the ROCs of AC and CAP for the detection of hepatic steatosis were 0.808 (95% CI: 0.682-0.900) and 0.829 (95% CI: 0.706-0.916), respectively, with the difference not being statistically significant (p = 0.762). AC showed 61.5% of sensitivity and 90.3% of specificity. AC was positively correlated with HFF (p < 0.001). HFF was the only factor significantly affecting AC. CONCLUSIONS: ATI showed moderate sensitivity and high specificity in the diagnosis and quantification of hepatic steatosis in low-grade steatosis without fibrosis. Only HFF significantly affected AC. KEY POINTS: • Attenuation imaging showed moderate sensitivity and high specificity performance in the diagnosis and quantification of hepatic steatosis in low-grade steatosis without fibrosis. • The diagnostic performance of the attenuation coefficient by attenuation imaging did not significantly differ from that of the controlled attenuation parameter by transient elastography in quantifying low-grade steatosis. • The histopathologically determined hepatic fat fraction was the only factor significantly affecting the attenuation coefficient.