Publications by authors named "Joon Koo Han"

494 Publications

Virtual noncontrast images derived from dual-energy CT for assessment of hepatic steatosis in living liver donors.

Eur J Radiol 2021 Mar 27;139:109687. Epub 2021 Mar 27.

Department of Radiology, Seoul National University Hospital, Seoul, South Korea; Department of Radiology, Seoul National University College of Medicine, Seoul, South Korea; Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, South Korea.

Purpose: This study aimed to investigate the correlation of attenuation between virtual noncontrast (VNC) and true noncontrast (TNC) CT images and compare the diagnostic performance for hepatic steatosis using MR spectroscopy (MRS) as the reference standard.

Methods: A total of 131 consecutive hepatic donor candidates who underwent dual-source dual-energy CT and MRS within one month from January 2018 to April 2019 were included. An MRS value > 5.8 % was regarded as substantial hepatic steatosis. The correlation of attenuation between TNC and VNC in the liver and spleen, and liver attenuation index (LAI), defined as hepatic minus splenic attenuation, was evaluated using Spearman's rank correlation. The diagnostic performance of the LAI for hepatic steatosis was compared using receiver operating characteristic analyses.

Results: Twenty-three candidates (17.6 %) had substantial hepatic steatosis. The median liver attenuation (66.7 [IQR, 63.5-70.9] vs. 63.5 [IQR, 60.3-66.9], p < .001) and LAI (12.9 [9.3-16.7] vs. 7.4 [3.9-11.9], p < .001) in the VNC were higher than those in the TNC. Hepatic attenuation (r = 0.93, p < .001), splenic attenuation (r = 0.55, p < .001), and LAI (r = 0.87, p < .001) were significantly correlated between TNC and VNC. Area under the curve of LAI in TNC and VNC were 0.88 (cutoff, LAI < 3.1) and 0.84 (cutoff, LAI < 10.1), respectively, indicating no statistically significant difference (p = 0.11).

Conclusion: The LAI of VNC is significantly correlated with that of TNC and might be feasible for diagnosing substantial hepatic steatosis in living liver donor candidates using different cutoff values of LAI.
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http://dx.doi.org/10.1016/j.ejrad.2021.109687DOI Listing
March 2021

Added value of [Ga]Ga-DOTA-TOC PET/CT for characterizing pancreatic neuroendocrine neoplasms: a comparison with contrast-enhanced CT and/or MRI in a large study cohort.

Eur Radiol 2021 Mar 31. Epub 2021 Mar 31.

Department of Radiology, Seoul National University Hospital, 101 Daehakro, Jongno-gu, Seoul, 110-744, Korea.

Objectives: To investigate an additional value of [Ga]Ga-DOTA-TOC PET/CT for characterizing suspected pancreatic neuroendocrine neoplasms (NENs) in a large study cohort.

Methods: This retrospective study included 167 patients who underwent [Ga]Ga-DOTA-TOC PET/CT for suspected pancreatic NENs detected by contrast-enhanced CT (n = 153) and/or MRI (n = 85). Two board-certified radiologists independently reviewed CT and/or MRI as well as [Ga]Ga-DOTA-TOC PET/CT and scored the probability of NEN on a 5-point scale. Radiologists' diagnostic performances with and without [Ga]Ga-DOTA-TOC PET/CT were compared using pathologic findings as the standard of reference.

Results: All 167 patients were pathologically diagnosed with NENs (n = 131) or non-NENs (n = 36) by surgery (n = 93) or biopsy (n = 74). The non-NEN group included focal pancreatitis (n = 7), gastrointestinal stromal tumor (n = 6), serous cystadenoma (n = 5), metastatic renal cell carcinoma (n = 4), intrapancreatic accessory spleen (n = 4), ductal adenocarcinoma (n = 3), solid pseudopapillary neoplasm (n = 2), intraductal papillary mucinous carcinoma (n = 1), adenosquamous carcinoma (n = 1), schwannoma (n = 1), paraganglioma (n = 1), and solitary fibrous tumor (n = 1). Radiologists' diagnostic performance significantly improved after the addition of [Ga]Ga-DOTA-TOC PET/CT (AUC of CT: 0.737 vs. 0.886 for reviewer 1 [p = 0.0004]; 0.709 vs. 0.859 for reviewer 2 [p = 0.0002], AUC of MRI: 0.748 vs. 0.872 for reviewer 1 [p = 0.023]; 0.670 vs. 0.854 for reviewer 2 [p = 0.001]). [Ga]Ga-DOTA-TOC PET/CT significantly improved sensitivity (CT: 87.4% vs. 96.6% for reviewer 1 [p = 0.001]; 74.8% vs. 92.5% for reviewer 2 [p = 0.0001], MRI: 86.9% vs. 98.4% for reviewer 1 [p = 0.016]; 70.5% vs. 91.8% for reviewer 2 [p = 0.002]).

Conclusions: [Ga]Ga-DOTA-TOC PET/CT provided an additional value over conventional CT or MRI for the characterization of suspected pancreatic NENs.

Key Points: • [Ga]Ga-DOTA-TOC PET/CT could provide additional value over conventional CT and/or MRI for the exact characterization of suspected pancreatic NENs by increasing AUC values and sensitivity. • Diagnostic improvement was significant, especially in NENs showing an atypical enhancement pattern. • The inter-observer agreement was improved when [Ga]Ga-DOTA-TOC PET/CT was added to CT and/or MRI.
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http://dx.doi.org/10.1007/s00330-021-07859-0DOI Listing
March 2021

Preoperative assessment of the resectability of pancreatic ductal adenocarcinoma on CT according to the NCCN Guidelines focusing on SMA/SMV branch invasion.

Eur Radiol 2021 Mar 19. Epub 2021 Mar 19.

Department of Radiology, Seoul National University Hospital, 101 Daehakro, Jongno-gu, Seoul, 03080, South Korea.

Objectives: For patients with pancreatic adenocarcinoma (PAC), adequate determination of disease extent is critical for optimal management. We aimed to evaluate diagnostic accuracy of CT in determining the resectability of PAC based on 2020 NCCN Guidelines.

Methods: We retrospectively enrolled 368 consecutive patients who underwent upfront surgery for PAC and preoperative pancreas protocol CT from January 2012 to December 2017. The resectability of PAC was assessed based on 2020 NCCN Guidelines and compared to 2017 NCCN Guidelines using chi-square tests. Overall survival (OS) was estimated using the Kaplan-Meier method and compared using log-rank test. R0 resection-associated factors were identified using logistic regression analysis.

Results: R0 rates were 80.8% (189/234), 67% (71/106), and 10.7% (3/28) for resectable, borderline resectable, and unresectable PAC according to 2020 NCCN Guidelines, respectively (p < 0.001). The estimated 3-year OS was 28.9% for borderline resectable PAC, which was significantly lower than for resectable PAC (43.6%) (p = 0.004) but significantly higher than for unresectable PAC (0.0%) (p < 0.001). R0 rate was significantly lower in patients with unresectable PAC according to 2020 NCCN Guidelines (10.7%, 3/28) than in those with unresectable PAC according to the previous version (31.7%, 20/63) (p = 0.038). In resectable PAC, tumor size ≥ 3 cm (p = 0.03) and abutment to portal vein (PV) (p = 0.04) were independently associated with margin-positive resection.

Conclusions: The current NCCN Guidelines are useful for stratifying patients according to prognosis and perform better in R0 prediction in unresectable PAC than the previous version. Larger tumor size and abutment to PV were associated with margin-positive resection in patients with resectable PAC.

Key Points: • The updated 2020 NCCN Guidelines were useful for stratifying patients according to prognosis. • The updated 2020 NCCN Guidelines performed better in the prediction of margin-positive resection in unresectable cases than the previous version. • Tumor size ≥ 3 cm and abutment to the portal vein were associated with margin-positive resection in patients with resectable pancreatic adenocarcinoma.
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http://dx.doi.org/10.1007/s00330-021-07847-4DOI Listing
March 2021

Prediction of residual tumor and overall survival after first-line surgery in patients with pancreatic ductal adenocarcinoma using preoperative magnetic resonance imaging findings.

Acta Radiol 2021 Mar 8:284185121999998. Epub 2021 Mar 8.

Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea.

Background: Complete resection is the only potentially curative treatment in patients with pancreatic ductal adenocarcinoma (PDA) and is associated with a longer overall survival (OS) than incomplete resection of tumor. Hence, prediction of the resection status after surgery would help predict the prognosis of patients with PDA.

Purpose: To predict residual tumor (R) classification and OS in patients who underwent first-line surgery for PDA using preoperative magnetic resonance imaging (MRI).

Material And Methods: In this study, 210 patients with PDA who underwent MRI and first-line surgery were randomly categorized into a test group (n=150) and a validation group (n=60). The R classification was divided into R0 (no residual tumor) and R1/R2 (microscopic/macroscopic residual tumor). Preoperative MRI findings associated with R classification and OS were assessed by using logistic regression and Cox proportional hazard models. In addition, the prediction models for the R classification and OS were validated using calibration plots and C statistics.

Results: On preoperative MRI, portal vein encasement (odds ratio 4.755) was an independent predictor for R1/R2 resection (=0.040). Tumor size measured on MRI (hazard ratio [HR] per centimeter 1.539) was a predictor of OS, along with pathologic N1 and N2 stage (HR 1.944 and 3.243, respectively), R1/R2 resection (HR 3.273), and adjuvant chemoradiation therapy (HR 0.250) (<0.050). Calibration plots demonstrated satisfactory predictive performance.

Conclusion: Preoperative MRI was valuable for predicting R1/R2 resection using portal vein encasement. Tumor size measured on MRI was useful for the prediction of OS after first-line surgery for PDA.
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http://dx.doi.org/10.1177/0284185121999998DOI Listing
March 2021

2D shear wave elastography is better than transient elastography in predicting post-hepatectomy complication after resection.

Eur Radiol 2021 Jan 18. Epub 2021 Jan 18.

Department of Radiology, Chung-Ang University Hospital, Seoul, South Korea.

Objectives: Both transient elastography (TE) and 2D shear wave elastography (SWE) are accurate methods to evaluate liver fibrosis. We aimed to evaluate the diagnostic performance of 2D-SWE in predicting post-hepatectomy complication and to compare it with TE.

Methods: We prospectively enrolled 125 patients with liver tumors. Liver stiffness (LS) (kilopascal [kPa]) was measured using both TE and 2D-SWE before surgery. All post-operative complication was evaluated using the comprehensive complication index (CCI), and CCI ≥ 26.2 was defined as severe complication. Logistic regression analysis was performed to identify predictive factors for severe complication. Receiver operating characteristic analysis was used to evaluate the diagnostic performance of TE/2D-SWE in detecting liver fibrosis and severe complication.

Results: Severe complication developed in 18 patients. The median LS in patients with severe complication was significantly higher for both 2D-SWE (11.4 kPa vs. 7.0 kPa, p < 0.001) and TE (8.9 kPa vs. 6.2 kPa, p = 0.009). LS obtained from 2D-SWE was a significant factor correlated with severe complication (odds ratio: 1.27 per kPa [1.10-1.46], p = 0.001). The diagnostic performance of 2D-SWE was significantly higher than that of TE in detecting both ≥F3 (p = 0.024) and F4 (p = 0.048). The area under the curve of 2D-SWE to predict severe complication was 0.854, significantly higher than 0.692 of TE (p = 0.004). The optimal cut-off LS from 2D-SWE to predict severe complication was 8.6 kPa, with sensitivity of 88.9% (16/18) and specificity of 73.8% (79/107).

Conclusion: LS obtained from 2D-SWE was a significant predictive factor for severe complication, and 2D-SWE showed significantly a better diagnostic performance than TE in detecting liver fibrosis and severe complication.

Key Points: • The diagnostic performance of 2D-SWE was significantly higher than that of TE in detecting both ≥ F3 (AUC: 0.853 vs. 0.779, p = 0.024) and F4 (AUC: 0.929 vs. 0.872, p = 0.048). • Liver stiffness value obtained from 2D-SWE was a significant factor correlated with the development of severe complication defined as CCI ≥ 26.2 after hepatic resection for liver tumors (odds ratio: 1.27 per kPa [1.10-1.46], p = 0.001). • 2D-SWE provided significantly a better diagnostic performance in predicting severe complication after hepatic resection than TE (AUC for 2D-SWE: 0.853 vs. AUC for TE: 0.692, p = 0.004).
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http://dx.doi.org/10.1007/s00330-020-07662-3DOI Listing
January 2021

Reducing Pain by Artificial Ascites Infusion During Radiofrequency Ablation for Subcapsular Hepatocellular Carcinoma.

Cardiovasc Intervent Radiol 2021 Apr 3;44(4):565-573. Epub 2021 Jan 3.

Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.

Purpose: To evaluate therapeutic effects of artificial ascites (AA) infusion in patients with subcapsular hepatocellular carcinoma (HCC) treated with radiofrequency ablation (RFA) and to determine whether this infusion can reduce pain.

Methods And Materials: From 2011 to 2016, 123 patients with treatment-naïve single subcapsular HCC (≤ 2.5 cm) who underwent RFA were retrospectively included. Patients were divided into two groups according to AA infusion. After RFA, medical records were used to analyze pain scores during a 24-h period and to determine the opioid used that compared using Mann-Whitney U test. We also conducted subgroup analysis of the patients with HCCs located adjacent to parietal peritoneum. After follow-up period, we analyzed local tumor progression (LTP) and recurrence-free survival using Kaplan-Meier method.

Results: AA was infused in 76 patients (61.8%, 76/123). Pain score using numeric rating scale (NRS) was significantly lower in AA infusion group than in control group (2.54 ± 2.8 vs. 3.66 ± 3.2, p = 0.048). Dose of opioids used was not significantly different between two groups (1.62 ± 3.4 mg vs. 1.66 ± 3 mg, p = 0.698). However, in subgroup analysis (N = 45), NRS score and dose of opioids used were significantly lower in AA infusion group (p = 0.03, p = 0.032, respectively). LTP rate was not significantly different between two groups (p = 0.673).

Conclusion: AA infusion was an effective and safe way to reduce pain when performing RFA for subcapsular HCC. In particular, in patients with subcapsular HCC adjacent to parietal peritoneum, dose of opioid to use pain control was significantly lower with AA infusion.
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http://dx.doi.org/10.1007/s00270-020-02723-yDOI Listing
April 2021

Therapeutic response monitoring after targeted therapy in an orthotopic rat model of hepatocellular carcinoma using contrast-enhanced ultrasound: Focusing on inter-scanner, and inter-operator reproducibility.

PLoS One 2020 23;15(12):e0244304. Epub 2020 Dec 23.

Department of Radiology, Seoul National University Hospital, Jongno-gu, Seoul, Korea.

Purpose: To assess therapeutic response monitoring after targeted therapy in an orthotopic rat model of hepatocellular carcinoma (HCC) using CEUS with focusing on inter-scanner and inter-operator reproducibility.

Materials And Methods: For reproducibility, CEUS was performed using two different US scanners by two operators in sixteen rat models of HCC. Using perfusion analysis software (VueBox ®), eleven parameters were collected, and intra-class correlation coefficient (ICC) was used to analyze reproducibility. Then seventeen rat models of HCC were divided into treatment group (n = 8, 30 mg/kg/day sorafenib for five days) and control group (n = 9). CEUS was performed at baseline and 14 days after first treatment, and changes of perfusion parameters were analyzed.

Results: In treatment group, CEUS perfusion parameters showed a significant change. The peak enhancement (PE, 2.50 x103±1.68 x103 vs 5.55x102±4.65x102, p = 0.010) and wash-in and wash out AUC (WiWoAUC, 1.07x105±6.48 x104 vs 2.65x104±2.25x104, p = 0.009) had significantly decreased two weeks after treatment. On the contrary, control group did not show a significant change, including PE (1.15 x103±7.53x102 vs 9.43x102± 7.81 x102, p = 0.632) and WiWoAUC (5.09 x104±3.25x104 vs 5.92 x104±3.20x104, p = 0.646). For reproducibility, the various degrees of inter-scanner reproducibility were from poor to good (ICC: <0.01-0.63). However, inter-operator reproducibility of important perfusion parameters, including WiAUC, WoAUC, and WiWoAUC, ranged from fair to excellent (ICC: 0.59-0.93) in a different scanner.

Conclusion: Our results suggest that CEUS is useful for assessment of the treatment response after targeted therapy and with fair to excellent inter-operator reproducibility.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244304PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757904PMC
March 2021

Combined treatment of sorafenib and doxorubicin-loaded microbubble-albumin nanoparticle complex for hepatocellular carcinoma: A feasibility study.

PLoS One 2020 11;15(12):e0243815. Epub 2020 Dec 11.

Department of Radiology, Seoul National University Hospital, Jongno-gu, Seoul, Republic of Korea.

Purpose: To assess the feasibility of the combined sorafenib (SOR) and doxorubicin-loaded microbubble-albumin nanoparticle complex (DOX-MAC) treatment effect in an orthotopic rat model of hepatocellular carcinoma (HCC).

Materials And Methods: Sixty-two rats with N1-S1 hepatoma were divided into four groups according to the treatment methods, i.e. G1 (SOR and DOX-MAC; n = 12), G2 (SOR; n = 15), G3 (DOX-MAC; n = 12), G4 (DOX; n = 11), and G5 (normal saline; n = 12). We performed the theragnostic, contrast-enhanced ultrasound examination and treatment at the baseline, one-week, and two-weeks. Tumor volume and perfusion parameters were compared at each time point and the differences between all of the groups over time were analyzed using repeated measures ANOVA. We also analyzed the apoptotic index and microvessel density (MVD) per each tumor specimen in all of the groups.

Results: The tumors increased from the beginning in all of the groups to the final follow-up, whereas the tumor growth in the G1 group and the G2 group was inhibited during the treatment period compared to the baseline tumor volume (P = 0.016 and P = 0.031). The G1 group resulted in tumor growth inhibition compared to the control group (P = 0.008). The G1 group showed that the peak enhancement and wash-in area under the curve were lower than that of the G4 group (P = 0.010 and 0.022). However, there was no difference in perfusion parameters in the other treated group compared to control group. The MVD of the G1 group tumor was lower than that of the G4 group (P = .016).

Conclusion: Our results suggest that the combination therapy of SOR and DOX-MAC can cause inhibition of tumor growth after treatment and that this therapy can be adequately monitored using the theragnostic DOX-MAC agent.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243815PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732110PMC
January 2021

Role of Contrast-Enhanced Ultrasound as a Second-Line Diagnostic Modality in Noninvasive Diagnostic Algorithms for Hepatocellular Carcinoma.

Korean J Radiol 2021 03 3;22(3):354-365. Epub 2020 Nov 3.

Department of Radiology, Seoul National University Hospital, Seoul, Korea.

Objective: To investigate the diagnostic performance of contrast-enhanced ultrasound (CEUS) and its role as a second-line imaging modality after gadoxetate-enhanced MRI (Gd-EOB-MRI) in the diagnosis of hepatocellular carcinoma (HCC) among at risk observations.

Materials And Methods: We prospectively enrolled participants at risk of HCC with treatment-naïve solid hepatic observations (≥ 1 cm) of Liver Imaging Reporting and Data System (LR)-3/4/5/M during surveillance and performed Gd-EOB-MRI. A total of one hundred and three participants with 103 hepatic observations (mean size, 28.2 ± 24.5 mm; HCCs [n = 79], non-HCC malignancies [n = 15], benign [n = 9]; diagnosed by pathology [n = 57], or noninvasive method [n = 46]) were included in this study. The participants underwent CEUS with sulfur hexafluoride. Arterial phase hyperenhancement (APHE) and washout on Gd-EOB-MRI and CEUS were evaluated. The distinctive washout in CEUS was defined as mild washout 60 seconds after contrast injection. The diagnostic ability of Gd-EOB-MRI and of CEUS as a second-line modality for HCC were determined according to the European Association for the Study of the Liver (EASL) and the Korean Liver Cancer Association and National Cancer Center (KLCA-NCC) guidelines. The diagnostic abilities of both imaging modalities were compared using the McNemar's test.

Results: The sensitivity of CEUS (60.8%) was lower than that of Gd-EOB-MRI (72.2%, = 0.06 by EASL; 86.1%, < 0.01 by KLCA-NCC); however, the specificity was 100%. By performing CEUS on the inconclusive observations in Gd-EOB-MRI, HCCs without APHE (n = 10) or washout (n = 12) on Gd-EOB-MRI further presented APHE (80.0%, 8/10) or distinctive washout (66.7%, 8/12) on CEUS, and more HCCs were diagnosed than with Gd-EOB-MRI alone (sensitivity: 72.2% vs. 83.5% by EASL, < 0.01; 86.1% vs. 91.1% by KCLA-NCC, = 0.04). There were no false-positive cases for HCC on CEUS.

Conclusion: The addition of CEUS to Gd-EOB-MRI as a second-line diagnostic modality increases the frequency of HCC diagnosis without changing the specificities.
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http://dx.doi.org/10.3348/kjr.2020.0973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909851PMC
March 2021

Hepatobiliary phase of gadoxetic acid-enhanced MRI in patients with HCC: prognostic features before resection, ablation, or TACE.

Eur Radiol 2020 Nov 19. Epub 2020 Nov 19.

Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Objectives: Patients with hepatocellular carcinoma (HCC) receiving different treatments might have specific prognostic factors that can be captured in the hepatobiliary phase (HBP) of gadoxetic acid-enhanced magnetic resonance imaging (GA-MRI). We aimed to identify the clinical findings and HBP features with prognostic value in patients with HCC.

Methods: In this retrospective, single-institution study, we included patients with Barcelona Clinic Liver Cancer very early/early stage HCC who underwent GA-MRI before treatment. After performing propensity score matching, 183 patients received the following treatments: resection, radiofrequency ablation (RFA), and transarterial chemoembolization (TACE) (n = 61 for each). Cox regression models were used to identify clinical factors and HBP features associated with disease-free survival (DFS) and overall survival (OS).

Results: In the resection group, large tumor size was associated with poor DFS (hazard ratio [HR] 4.159 per centimeter; 95% confidence interval [CI], 1.669-10.365) and poor OS (HR 8.498 per centimeter; 95% CI, 1.072-67.338). In the RFA group, satellite nodules on HBP images were associated with poor DFS (HR 5.037; 95% CI, 1.061-23.903) and poor OS (HR 9.398; 95% CI, 1.480-59.668). Peritumoral hypointensity on HBP images was also associated with poor OS (HR 13.062; 95% CI, 1.627-104.840). In addition, serum albumin levels and the prothrombin time-international normalized ratio were associated with DFS and/or OS. Finally, in the TACE group, no variables were associated with DFS/OS.

Conclusions: Different HBP features and clinical factors were associated with DFS/OS among patients with HCC receiving different treatments.

Key Points: • In patients who underwent resection for HCC, a large tumor size on HBP images was associated with poor disease-free survival and overall survival. • In the RFA group, satellite nodules and peritumoral hypointensity on HBP images, along with decreased serum albumin levels and PT-INR, were associated with poor disease-free survival and/or overall survival. • In the TACE group, no clinical or HBP imaging features were associated with disease-free survival or overall survival.
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http://dx.doi.org/10.1007/s00330-020-07499-wDOI Listing
November 2020

Important CT and histopathological findings for recurrence and overall survival in patients with pancreatic ductal adenocarcinoma who underwent surgery after neoadjuvant FOLFIRINOX.

Eur Radiol 2020 Nov 17. Epub 2020 Nov 17.

Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Objectives: To investigate important factors for recurrence-free survival (RFS) and overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDA) who underwent surgery after neoadjuvant FOLFIRINOX using CT and histopathological findings.

Materials And Methods: Sixty-nine patients with PDA who underwent surgery after neoadjuvant FOLFIRINOX were retrospectively included. All patients underwent baseline and first follow-up CT. Two reviewers assessed the CT findings and resectability based on the NCCN guideline. They graded extrapancreatic perineural invasion (EPNI) using a 3-point scale focused on 5 routes. Clinical and histopathological results, such as T- and N-stage, tumor regression grade (TRG) using the College of American Pathology (CAP) grading system, and resection status, were also investigated. Kaplan-Meier methods were used for RFS and OS. The Cox proportional hazard model and logistic regression model were used to identify significant predictive factors.

Results: There were 57 patients (82.6%) without residual tumors (R0) and 12 patients (17.4%) with residual tumors (R1 or R2). The median RFS was 13 months (range 0~22 months). For RFS, EPNI on baseline CT (hazard ratio (HR) 2.53, 95% confidence interval (CI) 1.116-5.733, p = 0.026) and TRG (HR 1.76, 95% CI 1.000-3.076, p = 0.046) were important predictors of early recurrence. The mean OS was 48 months (range 11~35 months). For OS, TRG (HR 1.05, 95% CI 1.251-6.559, p = 0.013) was a significant factor. However, there were no independent predictors for residual tumors according to the CT findings.

Conclusion: EPNI on baseline CT and TRG were important prognostic factors for tumor recurrence. In addition, TRG was also an important prognostic factor for OS.

Key Points: • CT and histopathological findings are helpful for predicting early recurrence and poor survival. • EPNI on baseline CT (HR 2.53, p = 0.026) is an important predictor of early recurrence. • The TRG is an important prognostic factor for early recurrence (HR 1.76, p = 0.046) and poor survival (HR 1.05, p = 0.013).
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http://dx.doi.org/10.1007/s00330-020-07489-yDOI Listing
November 2020

Assessment of malignant potential in intraductal papillary mucinous neoplasms of the pancreas using MR findings and texture analysis.

Eur Radiol 2021 May 2;31(5):3394-3404. Epub 2020 Nov 2.

Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.

Objectives: To investigate the utility of MR findings and texture analysis for predicting the malignant potential of pancreatic intraductal papillary mucinous neoplasms (IPMNs).

Methods: Two hundred forty-eight patients with surgically confirmed IPMNs (106 malignant [invasive carcinoma/high-grade dysplasia] and 142 benign [low/intermediate-grade dysplasia]) and who underwent magnetic resonance imaging (MRI) with MR cholangiopancreatography (MRCP) were included. Two reviewers independently analyzed MR findings as proposed by the 2017 international consensus guidelines. Texture analysis of MRCP was also performed. A multivariate logistic regression analysis was used to identify predictors for malignant IPMNs. Diagnostic performance was also analyzed using receiver operating curve analysis.

Results: Among MR findings, enhancing mural nodule size ≥ 5 mm, main pancreatic duct (MPD) ≥ 10 mm or MPD of 5 to 9 mm, and abrupt change of MPD were significant predictors for malignant IPMNs (p < 0.05). Among texture variables, significant predictors were effective diameter, surface area, sphericity, compactness, entropy, and gray-level co-occurrence matrix entropy (p < 0.05). At multivariate analysis, enhancing mural nodule ≥ 5 mm (odds ratios (ORs), 6.697 and 6.968, for reviewers 1 and 2, respectively), MPD ≥ 10 mm or MPD of 5 to 9 mm (ORs, 4.098 and 4.215, and 2.517 and 3.055, respectively), larger entropy (ORs, 1.485 and 1.515), and smaller compactness (ORs, 0.981 and 0.977) were significant predictors for malignant IPMNs (p < 0.05). When adding texture variable to MR findings, diagnostic performance for predicting malignant IPMNs improved from 0.80 and 0.78 to 0.85 and 0.85 in both reviewers (p < 0.05), respectively.

Conclusions: MRCP-derived texture features are useful for predicting malignant IPMNs, and the addition of texture analysis to MR features may improve diagnostic performance for predicting malignant IPMNs.

Key Points: • Among the MR imaging findings, an enhancing mural nodule size ≥ 5 mm and dilated main pancreatic ducts are independent predictors for malignant IPMNs. • Greater entropy and smaller compactness on MR texture analysis are independent predictors for malignant IPMNs. • The addition of MR texture analysis improved the diagnostic performance for predicting malignant IPMNs from 0.80 and 0.78 to 0.85 and 0.85, respectively.
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http://dx.doi.org/10.1007/s00330-020-07425-0DOI Listing
May 2021

Prediction of tumor recurrence and poor survival of ampullary adenocarcinoma using preoperative clinical and CT findings.

Eur Radiol 2021 Apr 30;31(4):2433-2443. Epub 2020 Sep 30.

Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Objectives: To predict poor survival and tumor recurrence in patients with ampullary adenocarcinoma using preoperative clinical and CT findings.

Materials And Methods: A total of 216 patients with ampullary adenocarcinoma who underwent preoperative CT and surgery were retrospectively included. CT was assessed by two radiologists. Clinical and histopathological characteristics including histologic subtypes were investigated. A Cox proportional hazard model and the Kaplan-Meier method were used to identify disease-free survival (DFS) and overall survival (OS). A nomogram was created based on the multivariate analysis. The optimal cutoff size of the tumor was evaluated and validated by internal cross validation.

Results: The median OS was 62.8 ± 37.9, and the median DFS was 54.3 ± 41.2 months. For OS, tumor size (hazard ratio [HR] 2.79, p < 0.001), papillary bulging (HR 0.63, p = 0.049), organ invasion on CT (HR 1.92, p = 0.04), male sex (HR 1.59, p = 0.046), elevated CA 19-9 (HR 1.92, p = 0.01), pT stage (HR 2.45, p = 0.001), and pN stage (HR 3.04, p < 0.001) were important predictors of survival. In terms of recurrence, tumor size (HR 2.37, p = 0.04), pT stage (HR 1.76, p = 0.03), pN stage (HR 2.23, p = 0.001), and histologic differentiation (HR 4.31, p = 0.008) were important predictors of recurrence. In terms of tumor size on CT, 2.65 cm and 3.15 cm were significant cutoff values for poor OS and RFS (p < 0.001).

Conclusion: Preoperative clinical and CT findings were useful to predict the outcomes of ampullary adenocarcinoma. In particular, tumor size, papillary bulging, organ invasion on CT, male sex, and elevated CA 19-9 were important predictors of poor survival after surgery.

Key Points: • Clinical staging based on preoperative clinical information and CT findings can be useful to predict the prognosis of ampullary adenocarcinoma patients. • In terms of survival, tumor size (HR 2.79), papillary bulging (HR 0.63), organ invasion on CT (HR 1.92), male sex (HR 1.59), and elevated CA 19-9 (HR 1.92) were important clinical predictors of poor survival. • Tumor size on CT was of special importance for both poor overall survival and disease-free survival, with optimal cutoff values of 2.65 cm and 3.15 cm, respectively (p < 0.001).
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http://dx.doi.org/10.1007/s00330-020-07316-4DOI Listing
April 2021

Intra-individual comparison of dual portal venous phases for non-invasive diagnosis of hepatocellular carcinoma at gadoxetic acid-enhanced liver MRI.

Eur Radiol 2021 Feb 26;31(2):824-833. Epub 2020 Aug 26.

Department of Radiology, Seoul National University Hospital, Seoul, South Korea.

Objectives: To compare the diagnostic performances of first and second portal venous phases (PVP1 and PVP2) in revealing washout and capsule appearance for non-invasive HCC diagnoses in gadoxetic acid-enhanced MRI (Gd-EOB-MRI).

Methods: This retrospective study included 123 at-risk patients with 160 hepatic observations (HCCs, n = 116; non-HCC malignancies, n = 18; benign, n = 26) showing arterial phase hyper-enhancement (APHE) ≥ 1 cm at Gd-EOB-MRI. The mean time intervals from gadoxetic acid injection to PVP1 and PVP2 acquisitions were 53 ± 2 s and 73 ± 3 s, respectively. After evaluating image findings independently, imaging findings and diagnoses were finalized by a consensus of two radiologists using either PVP1 or PVP2 image sets according to the LI-RADS v2018 or EASL criteria. Sensitivity, specificity, and accuracy were compared.

Results: Among HCCs, more washout and enhancing capsule were observed in PVP2 (83.6% and 27.6%) than in PVP1 (50.9% and 19.8%) (p < 0.001, both). The PVP2 set presented significantly higher sensitivity (83.6% vs. 53.5%, LI-RADS; 82.8% vs. 50.0%, EASL; p < 0.001, both) and accuracy (0.88 vs. 0.73, LI-RADS; 0.88 vs. 0.72, EASL; p < 0.001, both) than the PVP1 set without significant specificity loss (93.2% vs. 93.2%, by LI-RADS or EASL; p = 0.32, both). None of the non-HCC malignancy was non-invasively diagnosed as HCC in both PVP image sets.

Conclusion: Late acquisition of PVP detected washout and enhancing capsule of HCC more sensitively than early acquisition, enabling accurate diagnoses of HCC, according to LI-RADS or EASL criteria.

Key Points: • Among HCCs, more washout and enhancing capsules were observed in PVP2 than PVP1, quantitatively and qualitatively. • The portal venous phase acquired at around 70 s after contrast media administration (PVP2) provided significantly higher sensitivity and AUC value than PVP1 by using LI-RADS v2018 or EASL criteria. • More HCCs were categorized as LR-5 in PVP2 than in PVP1 images, and the specificity of PVP2 (93.5%) was comparable with PVP1 (93.5%).
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http://dx.doi.org/10.1007/s00330-020-07162-4DOI Listing
February 2021

Synergistic Effects of Pulsed Focused Ultrasound and a Doxorubicin-Loaded Microparticle-Microbubble Complex in a Pancreatic Cancer Xenograft Mouse Model.

Ultrasound Med Biol 2020 Nov 20;46(11):3046-3058. Epub 2020 Aug 20.

Department of Radiology and Institute of Radiation Medicine, Seoul National University Hospital, Seoul, Korea; Department of Radiology, Seoul National University College of Medicine, Seoul, Korea.

The synergistic effects of a doxorubicin (Dox)-loaded microparticle-microbubble complex (DMMC) and focused ultrasound (FUS) with a short duty cycle (5%) were evaluated in a pancreatic cancer xenograft model established by inoculating immunodeficient mice with CFPAC-1 cells. The efficacy of the DMMC with FUS (study 1), the effect of conjugating the particles as opposed to mixing them (study 2) and the levels of tumor apoptosis and intracellular Dox (study 3) were evaluated. The DMMC with FUS exhibited the lowest tumor growth rate (30.8 mm/wk) and the highest intracellular Dox uptake (8.8%) and tumor cell apoptosis rate (58.7%) among all treatments. DMMC had a significantly lower growth rate than the mixture of Dox-loaded microparticles and microbubbles (44.2 mm/wk, p < 0.01) when they were combined with FUS. In conclusion, DMMC with short-duty-cycle FUS holds promise for tumor growth suppression, which may be attributed to high intracellular Dox uptake.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2020.07.019DOI Listing
November 2020

Contrast-enhanced US with Sulfur Hexafluoride and Perfluorobutane for the Diagnosis of Hepatocellular Carcinoma in Individuals with High Risk.

Radiology 2020 10 4;297(1):108-116. Epub 2020 Aug 4.

From the Departments of Radiology (H.J.K., J.M.L., J.H.Y., J.K.H.) and Pathology (K.L., H.K.), Seoul National University Hospital, Seoul, Korea; Department of Radiology, Seoul National University College of Medicine, 101 Daehangno, Jongno-gu, Seoul, 03080, Korea (H.J.K., J.M.L., J.H.Y., J.K.H.); and Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Korea (J.M.L., J.K.H.).

Background Perfluorobutane (PFB) and sulfur hexafluoride (SHF) have different physiologic characteristics, but it is unclear whether hepatocellular carcinomas (HCCs) show similar wash-in and washout patterns to both contrast agents at US. Purpose To investigate Contrast-Enhanced US Liver Imaging Reporting and Data System (LI-RADS) version 2017 HCC categorization by comparing PFB-enhanced US and SHF-enhanced US in participants at high risk for HCC. Materials and Methods In this prospective study conducted from February to August 2019, participants at high risk for HCC with treatment-naive hepatic observations (≥1 cm) categorized as LR-3, LR-4, LR-5, or LR-M (intermediate probability of HCC, probable HCC, definitely HCC, and probably malignant but not HCC specific, respectively) on cross-sectional images were screened. They underwent same-day PFB-enhanced US and SHF-enhanced US. Arterial phase hyperenhancement (APHE), washout time and degree, and echogenicity in the Kupffer phase (PFB-enhanced US) were evaluated and categorized by the operator using CEUS LI-RADS, who referred to the radiologist who performed the contrast-enhanced US, and by a reviewer. Diagnostic performance was analyzed using the McNemar test. Results Fifty-nine participants were evaluated (43 with HCC, 10 with non-HCC malignancies, six with benign findings). Nonrim APHE was identically observed in 95% (41 of 43, operator) or 88% (38 of 43, reviewer) of HCCs with both contrast agents. Among 43 HCCs, late (≥60 seconds) and mild washout were more frequent with PFB-enhanced US (34 with operator, 33 with reviewer) than with SHF-enhanced US (24 with operator, 26 with reviewer) ( = .04 or = .12). The washout time for HCCs was later at PFB-enhanced US (median, 101 seconds ± 11) than at SHF-enhanced US (median, 84 seconds ± 5; = .04). Sensitivity (34 of 43; 79%; 95% confidence interval [CI]: 64%, 90%) was higher with PFB-enhanced US than with SHF-enhanced US (23 of 43; 54%; 95% CI: 38%, 67%; = .01). Specificity was 100% (95% CI: 79%, 100%) with both. Hypoenhancement in the Kupffer phase was more common in malignant (49 of 53 [92%] for both operator and reviewer) than in benign (two of six [33%] for operator, one of six [16%] for reviewer) lesions. Conclusion On the basis of the Contrast-Enhanced US Liver Imaging Reporting and Data System version 2017 algorithm, noninvasive US diagnosis of hepatocellular carcinoma by using perfluorobutane-enhanced US had higher diagnostic performance than sulfur hexafluoride-enhanced US, without loss of specificity. © RSNA, 2020 See also the editorial by Kim and Jang in this issue.
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http://dx.doi.org/10.1148/radiol.2020200115DOI Listing
October 2020

Two-Dimensional-Shear Wave Elastography with a Propagation Map: Prospective Evaluation of Liver Fibrosis Using Histopathology as the Reference Standard.

Korean J Radiol 2020 12 27;21(12):1317-1325. Epub 2020 Jul 27.

Department of Radiology, Chung-Ang University Hospital, Seoul, Korea.

Objective: The aim of this study was to prospectively evaluate whether liver stiffness (LS) assessments, obtained by two-dimensional (2D)-shear wave elastography (SWE) with a propagation map, can evaluate liver fibrosis stage using histopathology as the reference standard.

Materials And Methods: We prospectively enrolled 123 patients who had undergone percutaneous liver biopsy from two tertiary referral hospitals. All patients underwent 2D-SWE examination prior to biopsy, and LS values (kilopascal [kPa]) were obtained. On histopathologic examination, fibrosis stage (F0-F4) and necroinflammatory activity grade (A0-A4) were assessed. Multivariate linear regression analysis was performed to determine the significant factors affecting the LS value. The diagnostic performance of the LS value for staging fibrosis was assessed using receiver operating characteristic (ROC) analysis, and the optimal cut-off value was determined by the Youden index.

Results: Reliable measurements of LS values were obtained in 114 patients (92.7%, 114/123). LS values obtained from 2D-SWE with the propagation map positively correlated with the progression of liver fibrosis reported from histopathology ( < 0.001). According to the multivariate linear regression analysis, fibrosis stage was the only factor significantly associated with LS ( < 0.001). The area under the ROC curve of LS from 2D-SWE with the propagation map was 0.773, 0.865, 0.946, and 0.950 for detecting F ≥ 1, F ≥ 2, F ≥ 3, and F = 4, respectively. The optimal cut-off LS values were 5.4, 7.8, 9.4, and 12.2 kPa for F ≥ 1, F ≥ 2, F ≥ 3, and F = 4, respectively. The corresponding sensitivity and specificity of the LS value for detecting cirrhosis were 90.9% and 88.4%, respectively.

Conclusion: The LS value obtained from 2D-SWE with a propagation map provides excellent diagnostic performance in evaluating liver fibrosis stage, determined by histopathology.
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http://dx.doi.org/10.3348/kjr.2019.0978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689142PMC
December 2020

Prognostic Value of Tumor Regression Grade on MR in Rectal Cancer: A Large-Scale, Single-Center Experience.

Korean J Radiol 2020 09;21(9):1065-1076

Department of Radiology, Seoul National University Hospital, Seoul, Korea.

Objective: To determine the prognostic value of MRI-based tumor regression grading (mrTRG) in rectal cancer compared with pathological tumor regression grading (pTRG), and to assess the effect of diffusion-weighted imaging (DWI) on interobserver agreement for evaluating mrTRG.

Materials And Methods: Between 2007 and 2016, we retrospectively enrolled 321 patients (male:female = 208:113; mean age, 60.2 years) with rectal cancer who underwent both pre-chemoradiotherapy (CRT) and post-CRT MRI. Two radiologists independently determined mrTRG using a 5-point grading system with and without DWI in a one-month interval. Two pathologists graded pTRG using a 5-point grading system in consensus. Kaplan-Meier estimation and Cox-proportional hazard models were used for survival analysis. Cohen's kappa analysis was used to determine interobserver agreement.

Results: According to mrTRG on MRI with DWI, there were 6 mrTRG 1, 48 mrTRG 2, 109 mrTRG 3, 152 mrTRG 4, and 6 mrTRG 5. By pTRG, there were 7 pTRG 1, 59 pTRG 2, 180 pTRG 3, 73 pTRG 4, and 2 pTRG 5. A 5-year overall survival (OS) was significantly different according to the 5-point grading mrTRG ( = 0.024) and pTRG ( = 0.038). The 5-year disease-free survival (DFS) was significantly different among the five mrTRG groups ( = 0.039), but not among the five pTRG groups ( = 0.072). OS and DFS were significantly different according to post-CRT MR variables: extramural venous invasion after CRT (hazard ratio = 2.259 for OS, hazard ratio = 5.011 for DFS) and extramesorectal lymph node (hazard ratio = 2.610 for DFS). For mrTRG, k value between the two radiologists was 0.309 (fair agreement) without DWI and slightly improved to 0.376 with DWI.

Conclusion: mrTRG may predict OS and DFS comparably or even better compared to pTRG. The addition of DWI on T2-weighted MRI may improve interobserver agreement on mrTRG.
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http://dx.doi.org/10.3348/kjr.2019.0797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371618PMC
September 2020

Accuracy of Two-Dimensional Shear Wave Elastography and Attenuation Imaging for Evaluation of Patients With Nonalcoholic Steatohepatitis.

Clin Gastroenterol Hepatol 2021 Apr 22;19(4):797-805.e7. Epub 2020 May 22.

Department of Radiology, Chung-Ang University Hospital, Seoul, Republic of Korea.

Background & Aims: We evaluated the accuracy of a multiparametric approach using attenuation imaging and 2-dimensional shear wave elastography (2D-SWE) for the detection of steatosis and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD).

Methods: We studied 102 patients with increased levels of liver enzymes or suspicion of NAFLD, examined by attenuation imaging and 2D-SWE, immediately before biopsy collection and analysis (reference standard), from January 2018 to July 2019. We collected data on the attenuation coefficient (dB/cm/MHz) from attenuation imaging, liver stiffness measurements, and shear wave dispersion slope (SWDS, [m/s]/kHz) from 2D-SWE. Multivariate linear regression analysis was performed to identify factors associated with each parameter. Diagnostic performance was determined from area under the receiver operating curve (AUROC) values.

Results: The attenuation coefficient was associated with steatosis grade (P < .01) and identified patients with steatosis grades S1 or higher, S2 or higher, and S3 or higher, with AUROC values of 0.93, 0.88, and 0.83, respectively. Liver stiffness associated with fibrosis stage (P < .01) and lobular inflammatory activity was the only factor associated with SWDS (P < .01). SWDS detected inflammation grades I1 or higher, I2 or higher, and I3 or higher with AUROC values of 0.89, 0.85, and 0.78, respectively. We developed a risk scoring system to detect steatohepatitis based on the attenuation coefficient (score of 1 for 0.64 < attenuation coefficient ≤ 0.70; score of 2 for 0.70 < attenuation coefficient ≤ 0.73; and score of 3 for attenuation coefficient >0.73) and SWDS (score of 2 for 10.5 [m/s]/kHz < SWDS ≤ 11.7 [m/s]/kHz; and score of 3 for SWDS >11.7 [m/s]/kHz), using an unweighted sum of each score. Based on histopathology analysis, 55 patients had steatohepatitis. Risk scores correlated with NAFLD activity score (rho = 0.73; P < .01). Our scoring system identified patients with steatohepatitis with an AUROC of 0.93-this value was significantly higher than that of other parameters (P < .05), except SWDS (AUROC, 0.89; P = .18).

Conclusions: In the evaluation of patients with suspected NAFLD, the attenuation coefficient can identify patients with steatosis and liver stiffness can detect fibrosis accurately. SWDS was associated significantly with lobular inflammation. We developed a risk scoring system based on the attenuation coefficient and SWDS that might be used to detect steatohepatitis.
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http://dx.doi.org/10.1016/j.cgh.2020.05.034DOI Listing
April 2021

Deep learning-based decision support system for the diagnosis of neoplastic gallbladder polyps on ultrasonography: Preliminary results.

Sci Rep 2020 05 7;10(1):7700. Epub 2020 May 7.

Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.

Ultrasonography (US) has been considered image of choice for gallbladder (GB) polyp, however, it had limitations in differentiating between nonneoplastic polyps and neoplastic polyps. We developed and investigated the usefulness of a deep learning-based decision support system (DL-DSS) for the differential diagnosis of GB polyps on US. We retrospectively collected 535 patients, and they were divided into the development dataset (n = 437) and test dataset (n = 98). The binary classification convolutional neural network model was developed by transfer learning. Using the test dataset, three radiologists with different experience levels retrospectively graded the possibility of a neoplastic polyp using a 5-point confidence scale. The reviewers were requested to re-evaluate their grades using the DL-DSS assistant. The areas under the curve (AUCs) of three reviewers were 0.94, 0.78, and 0.87. The DL-DSS alone showed an AUC of 0.92. With the DL-DSS assistant, the AUCs of the reviewer's improved to 0.95, 0.91, and 0.91. Also, the specificity of the reviewers was improved (65.1-85.7 to 71.4-93.7). The intraclass correlation coefficient (ICC) improved from 0.87 to 0.93. In conclusion, DL-DSS could be used as an assistant tool to decrease the gap between reviewers and to reduce the false positive rate.
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http://dx.doi.org/10.1038/s41598-020-64205-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205977PMC
May 2020

Quantitative Assessment of Fatty Liver using Ultrasound with Normalized Local Variance Technique.

Ultraschall Med 2020 Apr 22. Epub 2020 Apr 22.

Radiology, Chung Ang University Hospital, Seoul, Korea (the Republic of).

Purpose:  To assess the diagnostic performance of the normalized local variance (NLV) ultrasound technique in the detection of the fatty liver using histopathology as a reference standard.

Materials And Methods:  We prospectively enrolled 194 consecutive patients with clinical suspicion of diffuse liver disease or history of liver transplantation. Conventional grayscale ultrasound and NLV examinations were performed and immediately followed by liver biopsies. The degrees of fatty liver, necroinflammatory activity, and fibrosis stage were evaluated by histopathological assessment. The diagnostic performance of the NLV values in detecting each grade of fatty liver was determined using receiver operating characteristics analyses, and multivariate linear regression analyses were performed to identify variables significantly associated with the NLV values.

Results:  The number of patients in each degree of fatty liver and hepatic fibrosis was 118/37/26/13 and 81/68/24/6/14 for none/mild/moderate/severe steatosis and F0 / F1/F2 / F3/F4 fibrosis on histopathological examinations, respectively. The area under the receiver operating characteristics curve and optimal cut-off NLV value for detecting fatty liver of varying degrees were 0.911 and 1.095 for ≥ S1, 0.974 and 1.055 for ≥ S2, and 0.954 and 1.025 for ≥ S3, respectively. Multivariate analyses revealed that not fibrosis or inflammation but rather the degree of steatosis was associated with the NLV value.

Conclusion:  The NLV value demonstrated excellent diagnostic performance for detecting varying degrees of fatty liver, and the degree of steatosis on histopathological examinations was the only significant factor affecting the NLV value.
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http://dx.doi.org/10.1055/a-1143-3091DOI Listing
April 2020

Prediction of liver regeneration in recipients after living-donor liver transplantation in using preoperative CT texture analysis and clinical features.

Abdom Radiol (NY) 2020 11;45(11):3763-3774

Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Purpose: The aim of the study is to predict the rate of liver regeneration in recipients after living-donor liver transplantation using preoperative CT texture and shape analysis of the future graft.

Methods: 102 donor-recipient pairs who underwent living-donor liver transplantation using right lobe grafts were retrospectively included. We semi-automatically segmented the future graft from preoperative CT. The volume of the future graft (LV) was measured, and texture and shape analyses were performed. The graft liver was segmented from postoperative follow-up CT and the volume of the graft (LV) was measured. The regeneration index was defined by the following equation: [(LV-LV)/LV] × 100(%). We performed a stepwise, multivariate linear regression analysis to investigate the association between clinical, texture and shape parameters and the RI and to make the best-fit predictive model.

Results: The mean regeneration index was 47.5 ± 38.6%. In univariate analysis, the volume of the future graft, energy, effective diameter, surface area, sphericity, roundness, compactness1, and grey-level co-occurrence matrix contrast as well as several clinical parameters were significantly associated with the regeneration index (p < 0.05). The best-fit predictive model for the regeneration index made by multivariate analysis was as follows: Regeneration index (%) = 127.020-0.367 × effective diameter - 1.827 × roundness + 47.371 × recipient body surface area (m) + 12.041 × log(recipient white blood cell count) (× 10/μL)+ 18.034 (if the donor was female).

Conclusion: The effective diameter and roundness of the future graft were associated with liver regeneration. Preoperative CT texture analysis of future grafts can be useful for predicting liver regeneration in recipients after living-donor liver transplantation.
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http://dx.doi.org/10.1007/s00261-020-02518-2DOI Listing
November 2020

Evaluation of a serum tumour marker-based recurrence prediction model after radiofrequency ablation for hepatocellular carcinoma.

Liver Int 2020 05 13;40(5):1189-1200. Epub 2020 Mar 13.

Department of Radiology, Seoul National University Hospital, Seoul, Korea.

Background & Aims: A recent study showed that serum tumour marker-based MoRAL score (11×√protein induced by vitamin K absence-II [PIVKA] +2×√alpha-foetoprotein [AFP]) can reflect both tumour burden and aggressiveness of hepatocellular carcinoma (HCC). This study aimed to evaluate whether baseline MoRAL score could predict tumour recurrence after radiofrequency ablation (RFA) for very-early/early-stage HCC.

Methods: A total of 576 HCC patients who underwent RFA as initial treatment were enrolled from two tertiary referral hospitals (256 in development cohort and 320 in validation cohort). The primary endpoint was recurrence-free survival (RFS) and the secondary endpoints included cumulative risks of intrahepatic distant recurrence (IDR) and extrahepatic metastasis (EM).

Results: In the development cohort, MoRAL score was an independent prognostic factor of RFS (P = .02). The optimal cutoff MoRAL score for predicting RFS was 68. Patients with high MoRAL score (>68) showed significantly shorter RFS than did those with low MoRAL score (hazard ratio [HR] = 2.04, P < .001). The 5-year RFS rates were 32.3% and 53.2% in high- and low-MoRAL groups respectively. Risks of both IDR (HR = 1.76, P = .003) and EM (HR = 8.25, P = .006) were also significantly higher in high MoRAL group. These results were reproduced in the validation cohort: RFS (HR = 1.81, P < .001; 5-year RFS rates = 27.7% vs 53.6%) was significantly shorter and risks of IDR (HR = 1.59, P = .003) and EM (HR = 6.19, P = .004) were significantly higher in high MoRAL group.

Conclusion: A high MoRAL score of >68 was significant a predictive factor of tumour recurrence after RFA for very-early/early-stage HCC. Moreover, it might be warranted to evaluate EM in patients with high baseline MoRAL scores.
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http://dx.doi.org/10.1111/liv.14406DOI Listing
May 2020

Differential and prognostic MRI features of gallbladder neuroendocrine tumors and adenocarcinomas.

Eur Radiol 2020 May 5;30(5):2890-2901. Epub 2020 Feb 5.

Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Objectives: To identify MRI features that are helpful for the differentiation of gallbladder neuroendocrine tumors (GB-NETs) from gallbladder adenocarcinomas (GB-ADCs) and to evaluate their prognostic values.

Methods: Between January 2008 and December 2018, we retrospectively enrolled patients who underwent MRI for GB malignancy. Two radiologists independently assessed the MRI findings and reached a consensus. Significant MRI features, which distinguish GB-NETs from GB-ADCs, were identified. Cox regression analyses were performed to find MRI features that were prognostic for overall survival.

Results: There were 63 patients with GB-NETs (n = 21) and GB-ADCs (n = 42). Compared with GB-ADCs, GB-NETs more frequently demonstrated the following MRI features: well-defined margins, intact overlying mucosa, and thick rim contrast enhancement and/or diffusion restriction (ps < 0.001). Liver metastases were more common and demonstrated thick rim contrast enhancement and diffusion restriction in GB-NETs (ps < 0.001). Lymph node (LN) metastasis showed thick rim diffusion restriction more often in GB-NETs than in GB-ADCs (p = 0.009). On quantitative analysis, the sizes of the GB mass and metastatic LNs in GB-NETs were larger than those in GB-ADCs (p = 0.002 and p = 0.010, respectively). The ratio of apparent diffusion coefficient values between the lesion and the spleen was lower in the GB mass, liver metastases, and LN metastases of GB-NETs than those of GB-ADCs (p < 0.001, p = 0.017, and p < 0.001, respectively). Survival analysis revealed that a large metastatic LN (hazard ratio 1.737; 95% confidence interval, 1.112-2.712) was the only poor prognostic factor (p = 0.015).

Conclusion: Several MRI features aided in differentiating between GB-NETs and GB-ADCs. A large metastatic LN was associated with poor survival.

Key Points: • Compared with gallbladder adenocarcinomas (GB-ADCs), neuroendocrine tumors (GB-NETs) and their metastases to the liver and lymph nodes more frequently demonstrated a thick rim appearance on contrast-enhanced MRI and diffusion-weighted images. • The ratio of apparent diffusion coefficient values between the lesion and the spleen was significantly lower for the primary mass, liver metastases, and lymph node metastases of GB-NETs than for those of GB-ADCs. • A large metastatic lymph node was the only poor prognostic factor for overall survival in patients with GB-NETs and GB-ADCs.
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http://dx.doi.org/10.1007/s00330-019-06588-9DOI Listing
May 2020

Application of computerized 3D-CT texture analysis of pancreas for the assessment of patients with diabetes.

PLoS One 2020 13;15(1):e0227492. Epub 2020 Jan 13.

Department of Radiology, Seoul National University Hospital, Seoul, Korea.

Objective: To evaluate the role of computerized 3D CT texture analysis of the pancreas as quantitative parameters for assessing diabetes.

Methods: Among 2,493 patients with diabetes, 39 with type 2 diabetes (T2D) and 12 with type 1 diabetes (T1D) who underwent CT using two selected CT scanners, were enrolled. We compared these patients with age-, body mass index- (BMI), and CT scanner-matched normal subjects. Computerized texture analysis for entire pancreas was performed by extracting 17 variable features. A multivariate logistic regression analysis was performed to identify the predictive factors for diabetes. A receiver operator characteristic (ROC) curve was constructed to determine the optimal cut off values for statistically significant variables.

Results: In diabetes, mean attenuation, standard deviation, variance, entropy, homogeneity, surface area, sphericity, discrete compactness, gray-level co-occurrence matrix (GLCM) contrast, and GLCM entropy showed significant differences (P < .05). Multivariate analysis revealed that a higher variance (adjusted OR, 1.002; P = .005), sphericity (adjusted OR, 1.649×104; P = .048), GLCM entropy (adjusted OR, 1.057×105; P = .032), and lower GLCM contrast (adjusted OR, 0.997; P < .001) were significant variables. The mean AUCs for each feature were 0.654, 0.689, 0.620, and 0.613, respectively (P < .05). In subgroup analysis, only larger surface area (adjusted OR, 1.000; P = .025) was a significant predictor for T2D.

Conclusions: Computerized 3D CT texture analysis of the pancreas could be helpful for predicting diabetes. A higher variance, sphericity, GLCM entropy, and a lower GLCM contrast were the significant predictors for diabetes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227492PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957148PMC
April 2020

Multiparametric MRI and F-FDG PET features for differentiating gastrointestinal stromal tumors from benign gastric subepithelial lesions.

Eur Radiol 2020 Mar 28;30(3):1634-1643. Epub 2019 Nov 28.

Department of Radiology, Seoul National University Hospital, 101 Daehakro, Jongno-gu, Seoul, Korea.

Objectives: To investigate whether multiparametric magnetic resonance imaging (MRI) and F-fluorodeoxyglucose positron emission tomography (PET) can be helpful in differentiating gastrointestinal stromal tumors (GISTs) from non-GISTs and high-risk GISTs from low-risk GISTs.

Methods: This retrospective study included 56 patients with pathologically confirmed GISTs (n = 39), leiomyoma (n = 8), schwannoma (n = 5), heterotopic pancreas (n = 3), and glomus tumor (n = 1) who underwent MRI and/or PET examinations. Two radiologists reviewed MRI regarding location, shape, contour, growth pattern, margin, signal intensity (SI) on T1- (T1WI) and T2-weighted images (T2WI), degree and pattern of enhancement, hemorrhage, and necrosis. Mean apparent diffusion coefficient (ADC) and maximum standardized uptake value (SUV) were measured. Imaging features were compared among non-GISTs, low-risk GISTs, and high-risk GISTs using uni- and multivariate statistical analyses.

Results: Size, longitudinal location, shape, contour, growth pattern, SI on T1- and T2WI, enhancement pattern, hemorrhage, necrosis, ADC, and SUV were significantly different among non-GISTs, low-risk GISTs, and high-risk GISTs (p < 0.05). On multivariate analysis, SI on T2WI (hazard ratio [HR], 66.0; p = 0.002) was the only independent variable for differentiating GISTs from non-GISTs whereas enhancement pattern (HR, 56.0; p = 0.041), ADC (HR, 0.997; p = 0.01), and SUV (HR, 2.08; p = 0.027) were significant features for differentiating between high-risk and low-risk GISTs.

Conclusions: Several qualitative and quantitative MRI and PET features including ADC and SUV values are significantly different among non-GISTs, low-risk GISTs, and high-risk GISTs. Multiparametric information obtained from MRI with or without PET can be useful for differentiation of gastric subepithelial tumors as well as for determining patients' management and prognosis.

Key Points: • Several qualitative MRI features are helpful in distinguishing gastrointestinal stromal tumors (GISTs) from non-GISTs as well as high-risk GISTs from low-risk GISTs. • Apparent diffusion coefficient value on diffusion-weighted imaging can be useful in distinguishing GISTs from non-GISTs as well as high-risk GISTs from low-risk GISTs. • PET has the potential to distinguish between high-risk and low-risk GISTs.
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http://dx.doi.org/10.1007/s00330-019-06534-9DOI Listing
March 2020

Portable ultrasound-guided high-intensity focused ultrasound with functions for safe and rapid ablation: prospective clinical trial for uterine fibroids-short-term and long-term results.

Eur Radiol 2020 Mar 8;30(3):1554-1563. Epub 2019 Nov 8.

Department of Radiology and the Institute of Radiation Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Objectives: To investigate the efficacy and safety of a new portable ultrasound-guided high-intensity focused ultrasound system (USgHIFU) with advanced targeting and beam steering technology for the treatment of uterine fibroids.

Methods: Fifty-nine uterine fibroids from 36 participants (mean age, 44.9 ± 4.1 years) were included from November 2013 to November 2015. All participants were treated with HIFU, with 3D electronic steering. MR imaging studies were performed before HIFU, immediately after HIFU, and 1 month and 3 (or 5) months after the HIFU treatment. The non-perfused volume ratio (NPVR), fibroid volume shrinkage (FVS), symptom improvement, quantified life quality assessment, and safety were analyzed. A long-term follow-up was conducted in July to December 2017 (mean, 32.2 months).

Results: The volume of the treated uterine fibroids ranged from 7.5 to 274.4 cm (mean, 69.8 cm; SD, 64.3 cm). The mean NPVR on the immediate post-HIFU MR imaging was 74.8 ± 25.2%. The mean FVS was 17.3% at 1 month, 33.3% at 3 months, and 45.1% at 5 months after HIFU treatment. The mean treatment time was 44.6 ± 28.2 min per fibroid and 72.9 ± 31.4 min per participant. Uterine fibroid-related symptoms and quality of life showed statistically significant improvement after the HIFU treatment. No significant symptoms related to safety or complications occurred. In the long-term follow-up, 78.8% of those surveyed were satisfied with their HIFU treatment.

Conclusion: This clinical trial showed that a portable USgHIFU with advanced functions may safely and effectively treat uterine fibroids.

Key Points: • A portable compact ultrasound-guided high-intensity focused ultrasound (HIFU) can effectively and safely treat uterine fibroids. • Advanced functions, such as portability, targeted forecasting, electronic beam steering, and interleaved scanning, might be helpful in enhancing the clinical applicability of ultrasound-guided high-intensity focused ultrasound. • In the long-term follow-up of more than 2 years, approximately 80% of those surveyed were satisfied with their HIFU treatment.
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http://dx.doi.org/10.1007/s00330-019-06468-2DOI Listing
March 2020

Non-invasive monitoring of hepatic steatosis via acoustic structure quantification of ultrasonography with MR spectroscopy as the reference standard.

Ultrasonography 2020 Jan 25;39(1):70-78. Epub 2019 Jun 25.

Department of Radiology, Seoul National University Hospital, Seoul, Korea.

Purpose: The purpose of this study was to prospectively evaluate whether monitoring hepatic steatosis by ultrasonography with acoustic structure quantification (ASQ) is feasible, using magnetic resonance spectroscopy (MRS) as the reference standard.

Methods: Thirty-six patients with suspected fatty liver disease underwent both untrasonography with ASQ and MRS on the same day. After a mean follow-up period of 11.4±2.5 months, follow-up ultrasonography with ASQ and MRS were performed on 27 patients to evaluate whether hepatic steatosis had improved. The focal disturbance (FD) ratio, as calculated using ASQ, and the hepatic fat fraction (HFF), estimated by MRS, were obtained at both initial and follow-up examinations. Pearson correlation coefficients were calculated to assess the correlations between ordinal values.

Results: The FD ratio showed a strong, negative linear correlation with the HFF after logarithmic transformation of both variables from the initial examinations of 36 patients (ρ=-0.888, P<0.001) and the follow-up examinations of 27 patients (ρ=-0.920, P<0.001). There was also a significant, negative linear correlation between the change in the logarithm of the FD ratio and the change in the logarithm of the HFF by MRS over the follow-up period (ρ=-0.645, P<0.001). In 16 patients with an increased FD ratio on follow-up, the HFF on follow-up MRS significantly decreased, and high-density lipoprotein levels significantly increased, whereas low-density lipoprotein levels tended to decrease.

Conclusion: The FD ratio was significantly correlated with the HFF at both the initial and follow-up examinations, and there was also a significant correlation between changes in the FD ratio and changes in the HFF over the follow-up period.
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http://dx.doi.org/10.14366/usg.19002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920624PMC
January 2020

Shear-Wave Dispersion Slope from US Shear-Wave Elastography: Detection of Allograft Damage after Liver Transplantation.

Radiology 2019 11 10;293(2):327-333. Epub 2019 Sep 10.

From the Departments of Radiology (D.H.L., J.Y.L., J.S.B., J.K.H.), Surgery (N.J.Y., K.W.L., K.S.S.), and Pathology (H.K., K.B.L.), Seoul National University Hospital, 101 Daehangno, Jongno-gu, Seoul 03080, Korea; and Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Korea (J.Y.L., J.K.H.).

Background Allograft damage (hepatic parenchymal damage) after liver transplant is associated with the degree of necroinflammation in graft liver. According to a recent animal study, shear-wave dispersion slope obtained at US shear-wave elastography (SWE) is associated with necroinflammatory activity in the liver. Purpose To evaluate the role of shear-wave dispersion slope in detecting allograft damage after liver transplant. Materials and Methods In this prospective study, 104 liver transplant recipients underwent percutaneous liver biopsy for allograft evaluation from December 2017 to November 2018. All participants underwent allograft SWE examination just before liver biopsy, and liver stiffness and shear-wave dispersion slope were obtained. Allograft damage was diagnosed by histopathologic analysis. Clinical and imaging factors related to liver stiffness and shear-wave dispersion slope were determined by multivariable linear regression analysis. Diagnostic performance of each variable in detecting allograft damage was evaluated by comparing area under the receiver operating curve (AUC) values. Results There were 104 study participants (35 women); median age was 56 years (interquartile range, 50-62 years). Allograft damage was found in 46 of 104 (44.2%) of participants. The median liver stiffness (8.2 kPa vs 6.3 kPa; < .01) and shear-wave dispersion slope (14.4 [m/sec]/kHz vs 10.4 [m/sec]/kHz; < .01) were higher in participants with allograft damage than in those without damage, respectively. Fibrosis stage was the only determinant factor for liver stiffness (coefficient, 1.8 kPa per fibrosis stage; 95% confidence interval: 0.1, 3.5; = .03), whereas both fibrosis stage (coefficient, 1.4 [m/sec]/kHz per fibrosis stage; 95% confidence interval: 0.3, 2.6; = .02) and necroinflammatory activity (coefficient, 1.6 [m/sec]/kHz per necroinflammatory activity grade; 95% confidence interval: 0.5, 2.7; < .01) affected shear-wave dispersion slope. The AUC for shear-wave dispersion slope in detecting allograft damage was 0.86, which was higher than that of liver stiffness (AUC, 0.75; < .01). Conclusion Shear-wave dispersion slope determined at US shear-wave elastography may help in detecting allograft damage after liver transplant. © RSNA, 2019
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http://dx.doi.org/10.1148/radiol.2019190064DOI Listing
November 2019