Publications by authors named "So Jung Lee"

93 Publications

Abbreviated magnetic resonance imaging vs ultrasound for surveillance of hepatocellular carcinoma in high-risk patients.

Liver Int 2021 Nov 24. Epub 2021 Nov 24.

Liver Cancer Center, Asan Medical Center, Seoul, Republic of Korea.

Background & Aims: We aimed to compare the performance of gadoxetic acid-enhanced abbreviated MRI (AMRI)-based surveillance and ultrasound-only surveillance in high-risk patients for hepatocellular carcinoma (HCC).

Methods: Prospectively recruited high-risk patients (>5% annual risk of HCC) who underwent one to three rounds of complete gadoxetic acid-enhanced MRI (CMRI) and ultrasound at 6-months intervals were retrospectively analysed. AMRI consisted of diffusion-weighted, T2-weighted, and hepatobiliary phase imaging. The sensitivity, specificity, and accuracy of CMRI followed by AMRI (CAA), AMRI-only (AAA), and ultrasound-only (US) were compared using generalized estimating equations. Image quality was assessed.

Results: In 382 patients, HCC was diagnosed in 43 (11.3%), including 42 with early-stage HCCs. The sensitivities of CAA (90.7%, 39/43) and AAA (86.0%, 37/43) were higher than US (27.9% [12/43]; P < 0.001), whereas the sensitivities of the two MRI approaches did not significantly differ (P = 0.56). The specificity of CAA (97.1%, 983/1012) was higher than AAA (95.6% [967/1012]; P = 0.01) and not significantly different from US (96.3% [975/1012]; P = 0.59). The CAA approach had the best accuracy of 96.9% (1022/1055), higher than the AAA approach (95.2% [1004/1055]; P = 0.01) and the US approach (93.6% [987/1055]; P = 0.01). Image quality was inadequate in 33.7% (356/1055) of US examinations but in only 10.0% (105/1055) of the AAA and 11.1% (117/1055) of the CAA approach.

Conclusions: In high-risk patients, AMRI-based surveillance approaches had higher sensitivities than ultrasound-only surveillance for early-stage HCC. A sequential MRI approach of CMRI followed by AMRIs showed superior accuracy than the AMRI-only or ultrasound-only approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.15110DOI Listing
November 2021

Liver-to-Spleen Volume Ratio Automatically Measured on CT Predicts Decompensation in Patients with B Viral Compensated Cirrhosis.

Korean J Radiol 2021 Dec 31;22(12):1985-1995. Epub 2021 Aug 31.

Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

Objective: Although the liver-to-spleen volume ratio (LSVR) based on CT reflects portal hypertension, its prognostic role in cirrhotic patients has not been proven. We evaluated the utility of LSVR, automatically measured from CT images using a deep learning algorithm, as a predictor of hepatic decompensation and transplantation-free survival in patients with hepatitis B viral (HBV)-compensated cirrhosis.

Materials And Methods: A deep learning algorithm was used to measure the LSVR in a cohort of 1027 consecutive patients (mean age, 50.5 years; 675 male and 352 female) with HBV-compensated cirrhosis who underwent liver CT (2007-2010). Associations of LSVR with hepatic decompensation and transplantation-free survival were evaluated using multivariable Cox proportional hazards and competing risk analyses, accounting for either the Child-Pugh score (CPS) or Model for End Stage Liver Disease (MELD) score and other variables. The risk of the liver-related events was estimated using Kaplan-Meier analysis and the Aalen-Johansen estimator.

Results: After adjustment for either CPS or MELD and other variables, LSVR was identified as a significant independent predictor of hepatic decompensation (hazard ratio for LSVR increase by 1, 0.71 and 0.68 for CPS and MELD models, respectively; < 0.001) and transplantation-free survival (hazard ratio for LSVR increase by 1, 0.8 and 0.77, respectively; < 0.001). Patients with an LSVR of < 2.9 (n = 381) had significantly higher 3-year risks of hepatic decompensation (16.7% vs. 2.5%, < 0.001) and liver-related death or transplantation (10.0% vs. 1.1%, < 0.001) than those with an LSVR ≥ 2.9 (n = 646). When patients were stratified according to CPS (Child-Pugh A vs. B-C) and MELD (< 10 vs. ≥ 10), an LSVR of < 2.9 was still associated with a higher risk of liver-related events than an LSVR of ≥ 2.9 for all Child-Pugh ( ≤ 0.045) and MELD ( ≤ 0.009) stratifications.

Conclusion: The LSVR measured on CT can predict hepatic decompensation and transplantation-free survival in patients with HBV-compensated cirrhosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3348/kjr.2021.0348DOI Listing
December 2021

MRI-guided radiotherapy for PVTT in HCC patients: evaluation of the efficacy and safety.

J Cancer Res Clin Oncol 2021 Sep 6. Epub 2021 Sep 6.

Department of Radiation Oncology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Purpose: This study aims to evaluate the efficacy, feasibility, and safety of the magnetic resonance imaging (MRI)-guided tumor tracking hypofractionated radiotherapy (HFRT) and stereotactic body radiation therapy (SBRT) for portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) patients.

Methods: We retrospectively reviewed the twelve cases of unresectable HCC with tumor thrombus in the main trunk or first branch of the portal vein that were treated with MRI-guided tumor tracking HFRT or SBRT using the ViewRay Linac MRIdian system between June 2019 and January 2021. The HFRT was performed with a total of 50 Gy in 10 fractions, and SBRT performed in a range of 36-50 Gy with 4-5 fractions. The median biologic effective dose (BED) with an a/b ratio of 10 was 75 Gy (range 68.4-100 Gy).

Results: The median follow-up duration was 5.0 months (range 1.9-12.8 months). Ten patients (83.3%) showed an objective response of PVTT. At the time of analysis, ten patients (83.3%) showed local control. The 1-year intrahepatic control rate was 48.9%. Three patients (25%) showed mild gastrointestinal symptoms, and there were no cases of grade 3 or higher toxicity. For hepatic toxicity, there were no cases in which the Child-Pugh score increased by more than two points after RT without disease progression.

Conclusion: MRI-guided tumor tracking HFRT and SBRT was a feasible, effective, and safe treatment option in HCC patients with tumor thrombi in the main trunk or first branch of the portal vein.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00432-021-03788-zDOI Listing
September 2021

Clinical outcome and toxicity of radiotherapy for inferior vena cava tumor thrombus in HCC patients: A retrospective study.

Medicine (Baltimore) 2021 Jun;100(25):e26390

Department of Radiation Oncology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Abstract: Hepatocellular carcinoma (HCC) involving the inferior vena cava rarely occurs, but its prognosis is extremely poor, with no established treatment to date. This study aimed to analyze the clinical outcome and toxicity of radiotherapy (RT) targeting inferior vena cava tumor thrombus (IVCTT) in HCC patients.From November 2011 to July 2020, medical record of 19 HCC patients who were treated with RT for IVCTT was retrospectively reviewed. RT was delivered using 3-dimensional conformal radiation therapy, intensity-modulated radiation therapy, and stereotactic body radiation therapy. The median radiation dose was 50 Gy (range, 45-55.8 Gy) for intensity-modulated radiation therapy and three-dimensional conformal radiotherapy. Stereotactic body radiation therapy was performed in 5 patients, for a total of 32 Gy in 4 fractions.The median follow-up duration was 8.1 months (range, 3.3-26.5 months). The median overall survival was 9.4 months (range, 3.7-26.5 months), and the 1-year overall survival rate was 37.1%. Eight of 19 patients (42.1%) had extrahepatic metastasis at the start of RT. Six of 11 patients (54.5%) who did not have extrahepatic metastasis at the start of RT showed extrahepatic metastasis after RT. The major cause of death was progression of extrahepatic metastasis (11 patients, 57.9%). The overall response rate of IVCTT for RT was 84.2%, and the local control rate at the time of the last follow-up was 89.4%. After RT, the most common first progression site was the lungs (9 patients, 47.4%). Most toxicities were grade 1 to 2 gastrointestinal (26.3%) and liver enzyme elevation (68.4%). Three patients occurred pulmonary embolism after RT later than 5 months after.RT is a feasible and safe local therapy for IVCTT, with favorable tumor control and acceptable toxicity. Extrahepatic metastasis is the major progression pattern and a leading cause of death in patients treated with RT. The combination of effective systemic therapy with RT may have to be considered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000026390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238290PMC
June 2021

Combined computed tomography and magnetic resonance imaging improves diagnosis of hepatocellular carcinoma ≤ 3.0 cm.

Hepatol Int 2021 Jun 6;15(3):676-684. Epub 2021 May 6.

Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea.

Background/purpose: Imaging diagnosis of hepatocellular carcinoma (HCC) is important, but the diagnostic performance of combined computed tomography (CT) and magnetic resonance imaging (MRI) using the Liver Imaging Reporting and Data System (LI-RADS) v2018 is not fully understood. We evaluated the clinical usefulness of combined CT and MRI for diagnosing HCC ≤ 3.0 cm using LI-RADS.

Methods: In 222 patients at risk of HCC who underwent both contrast-enhanced dynamic CT and gadoxetate disodium-enhanced MRI in 2017, 291 hepatic nodules ≤ 3.0 cm were retrospectively analyzed. Two radiologists performed image analysis and assigned a LI-RADS category to each nodule. The diagnostic performance for HCC was evaluated for CT, ordinary-MRI (washout confined to portal venous-phase), and modified-MRI (washout extended to hepatobiliary phase), and sensitivity and specificity were calculated for each modality. Generalized estimating equations were used to compare the diagnostic performance for HCC between combined CT and ordinary-MRI, combined CT and modified-MRI, and CT or MRI alone. p < 0.0062 (0.05/8) was considered statistically significant following Bonferroni correction for multiple comparisons.

Results: In 291 nodules, the sensitivity and specificity of CT, ordinary-MRI, and modified-MRI were 70.2% and 92.8%, 72.6% and 96.4%, and 84.6% and 88.0%, respectively. Compared with CT or MRI alone, both combined CT and ordinary-MRI (sensitivity, 83.7%; specificity, 95.2%) and combined CT and modified-MRI (sensitivity, 88.9%; specificity, 89.2%) showed significantly higher sensitivity (p ≤ 0.006), without a significant decrease in specificity (p ≥ 0.314).

Conclusions: Compared with CT or MRI alone, combined CT and MRI can increase sensitivity for diagnosing HCC ≤ 3.0 cm, without a significant decrease in specificity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12072-021-10190-xDOI Listing
June 2021

Value of discrepancy of the central scar-like structure between dynamic CT and gadoxetate disodium-enhanced MRI in differentiation of focal nodular hyperplasia and hepatocellular adenoma.

Eur J Radiol 2021 Jun 22;139:109730. Epub 2021 Apr 22.

Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

Purpose: To identify the value of discrepancies in the central scar (CS)-like structure between dynamic CT and gadoxetate disodium-enhanced MRI for differentiating FNH from HCA.

Methods: This retrospective study included 113 patients with pathologically-diagnosed FNH (n = 80) or HCA (n = 37). CS-like structures were evaluated on arterial phase (AP) CT and hepatobiliary phase (HBP) MRI. Presence of the CS-like structure, its discrepancy in visibility or size between AP CT and HBP MRI and between AP and HBP MRI, and features of non-scarred tumor portion were evaluated by two radiologists. Inter-observer agreement was evaluated by intraclass correlation coefficients (ICCs) and weighted kappa. Univariable and multivariable logistic regression and ROC analysis were performed to explore features differentiating FNH from HCA.

Results: Inter-observer agreement was moderate-to-excellent (ICCs≥0.74, kappa≥0.65). On univariable analysis, presence of CS-like structures (P < 0.001), discrepancy of the CS-like structures between AP CT and HBP MRI (73.8 % in FNH; 16.2 % in HCA, P < 0.001) and between AP and HBP MRI (70.0 % in FNH; 16.2 % in HCA, P < 0.001), and the features of non-scarred tumor portion (P ≤ 0.011) were significantly different between FNH and HCA. On multivariable analysis, the discrepancy of CS-like structures between AP CT and HBP MRI, and the absence of low SI of the non-scarred tumor portion on HBP MRI, were suggestive of FNH (P = 0.036 and P < 0.001, respectively; area under the ROC curve, 0.96 [95 % CI, 0.93-0.99]).

Conclusion: Evaluation of discrepancy in the visibility or size of CS-like structures between dynamic CT and gadoxetate disodium-enhanced MRI may facilitate the differentiation of FNH from HCA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejrad.2021.109730DOI Listing
June 2021

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

J Gastroenterol Hepatol 2021 Jul 5;36(7):1962-1970. Epub 2021 Mar 5.

Department of Radiation Oncology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Background And Aim: We compared the clinical outcomes of radiofrequency ablation (RFA) and stereotactic body radiation therapy (SBRT) in small (≤ 3 cm) hepatocellular carcinoma.

Methods: A total of 266 patients treated with RFA (n = 179) or SBRT (n = 87) were reviewed. Local control rates (LCRs), intrahepatic recurrence-free survival (IHRFS) rates, and overall survival (OS) rates were compared. Inverse probability of treatment weighting (IPTW) was used to adjust for imbalances in baseline characteristics between the two groups.

Results: The median follow-up period was 50.3 months, and treatment method (RFA vs SBRT) was not a significant prognostic factor for LCR, OS, and IHRFS in both multivariate and IPTW-adjusted analyses. The 4-year LCRs after RFA and SBRT were 92.7% and 95.0%, respectively. Perivascular location was a significant prognostic factor for LCR in the entire patients and in the RFA group, but not in the SBRT group. The 4-year OS rates in the RFA and SBRT groups were 78.1% and 64.1%, respectively (P = 0.012). After IPTW adjustment, the 4-year LCRs (90.6% vs 96.3%) and OS rates (71.8% vs 70.2%) were not significantly different between the two groups. The rate of grade ≥ 3 adverse events was 0.6% (n = 1) in the RFA group and 1.1% (n = 1) in the SBRT group.

Conclusions: The two treatment methods showed comparable outcomes in terms of LCR, OS rate, and IHRFS rate after IPTW adjustment. SBRT seems to be a viable alternative method for small hepatocellular carcinomas that are not suitable for RFA due to tumor location.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jgh.15442DOI Listing
July 2021

Interreader Reliability of Liver Imaging Reporting and Data System Treatment Response: A Systematic Review and Meta-Analysis.

Diagnostics (Basel) 2021 Feb 4;11(2). Epub 2021 Feb 4.

Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.

Background: For a proper management strategy in patients with locoregionally treated hepatocellular carcinoma (HCC), it is essential that the Liver Imaging Reporting and Data System (LI-RADS) treatment response algorithm (LR-TR) has high interreader reliability. We aimed to systematically evaluate the interreader reliability of LR-TR and sources of any study heterogeneity.

Methods: Original studies reporting the interreader reliability of LR-TR were identified in MEDLINE and EMBASE up to 20 September 2020. The pooled kappa coefficient (κ) was calculated using the DerSimonian-Laird random effects model. Subgroup analyses were performed according to imaging modality (magnetic resonance imaging (MRI) or computed tomography (CT)). Meta-regression analyses were performed to explore study heterogeneity.

Results: Eight studies with 851 HCCs were finally included. Pooled κ was 0.70 (95% CI, 0.58-0.82) for CT/MRI LR-TR, and those of MRI and CT were 0.71 (95% CI, 0.53-0.89) and 0.71 (95% CI, 0.65-0.78), respectively. Study design ( < 0.001) and type of treatment ( = 0.02) were significantly associated with substantial study heterogeneity.

Conclusion: LR-TR showed substantial interreader reliability regardless of the imaging modality. Because of substantial study heterogeneity, which was significantly associated with study design and type of treatment, published values for the interreader reliability of LR-TR should be interpreted with care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/diagnostics11020237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913820PMC
February 2021

The effect of adjuvant chemotherapy and early tumor regression on the outcome of nasopharyngeal cancer patients treated with concurrent chemoradiotherapy.

Oral Oncol 2021 02 25;113:105130. Epub 2021 Jan 25.

Department of Medical Oncology, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Objectives: We assessed the role of adjuvant chemotherapy (ACT) in patients with advanced nasopharyngeal carcinoma treated with concurrent chemoradiotherapy (CCRT) and investigated the prognostic factors for recurrence and survival.

Materials And Methods: Between January 2008 and January 2018, 88 non-metastatic nasopharyngeal carcinoma patients treated with CCRT and with or without ACT in two institutions were retrospectively reviewed. The initial tumor response evaluation was performed 1 month after CCRT completion. Survival analysis was performed for factors such as initial tumor regression, ACT and other clinical factors. Subgroup analysis was performed for the four-group categorized according to tumor regression and ACT (CR with/without ACT, non-CR with/without ACT).

Results: Complete response (CR) 1 month after CCRT was a favorable prognosticator for progression-free survival (PFS) (hazard ratio [HR] 3.16, 95% confidence interval [CI] 1.02-9.85, p = 0.046) and overall survival (OS) (HR 3.19, 95% CI 1.14-8.93, p = 0.027). Also, ACT was an independent factor for PFS (HR 0.38, 95% CI 0.15-0.98, p = 0.047) and OS (HR 0.37, 95% CI 0.13-0.99, p = 0.047). In subgroup analysis, the CR after CCRT followed by ACT group showed significantly higher locoregional recurrence-free survival (p = 0.02), OS (p = 0.003), distant-metastasis free survival (p = 0.07), and PFS (p = 0.01) than the other three groups.

Conclusion: Tumor regression 1 month after CCRT, and administration of ACT identified as an independent prognosticator for PFS and OS in this study. Even patients who show early tumor regression after CCRT may benefit from ACT. Further randomized trials should define the role of ACT in patients with nasopharyngeal cancer who achieved CR after CCRT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.oraloncology.2020.105130DOI Listing
February 2021

Accuracy of contrast-enhanced ultrasound liver imaging reporting and data system: a systematic review and meta-analysis.

Hepatol Int 2020 Dec 10;14(6):1104-1113. Epub 2020 Nov 10.

Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.

Background And Aim: After the introduction of the contrast-enhanced ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS), several studies have reported on its performance, but the reported data vary considerably. Therefore, we performed a systematic review and meta-analysis to determine the diagnostic performance of CEUS LI-RADS in patients at risk for hepatocellular carcinoma (HCC) and investigate the causes of study heterogeneity.

Methods: Original studies published until May 30, 2020, investigating the diagnostic performance of CEUS LI-RADS were identified in the MEDLINE, EMBASE, and Cochrane library databases. Study quality was assessed using the QUADAS-2 tool. Meta-analytic summary sensitivity and specificity for the diagnosis of HCC were calculated using a bivariate random-effects model. Meta-regression analysis was performed to explore the causes of study heterogeneity.

Results: Of the 105 articles screened, eight studies were finally analyzed (5428 hepatic observations). The summary sensitivity and specificity of CEUS LI-RADS category 5 (LR-5) for diagnosing HCC were 73% [95% confidence interval (CI) 65-79%; I = 93%] and 95% (95% CI 91-97%; I = 89%), respectively. Substantial study heterogeneity was noted in both sensitivity and specificity. Study heterogeneity was significantly associated with the proportion of cases of HCC and the type of reference standard (p ≤ 0.05).

Conclusion: CEUS LI-RADS had high pooled specificity for diagnosing HCC but suboptimal pooled sensitivity. Substantial study heterogeneity was found, which was significantly associated with the proportion of cases of HCC and the type of reference standard.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12072-020-10102-5DOI Listing
December 2020

An index based on deep learning-measured spleen volume on CT for the assessment of high-risk varix in B-viral compensated cirrhosis.

Eur Radiol 2021 May 30;31(5):3355-3365. Epub 2020 Oct 30.

Department of Brain and Cognitive Engineering, Korea University, 145 Anam-ro, Anam-dong, Seongbuk-gu, Seoul, 02841, South Korea.

Objectives: Deep learning enables an automated liver and spleen volume measurements on CT. The purpose of this study was to develop an index combining liver and spleen volumes and clinical factors for detecting high-risk varices in B-viral compensated cirrhosis.

Methods: This retrospective study included 419 patients with B-viral compensated cirrhosis who underwent endoscopy and CT from 2007 to 2008 (derivation cohort, n = 239) and from 2009 to 2010 (validation cohort, n = 180). The liver and spleen volumes were measured on CT images using a deep learning algorithm. Multivariable logistic regression analysis of the derivation cohort developed an index to detect endoscopically confirmed high-risk varix. The cumulative 5-year risk of varix bleeding was evaluated with patients stratified by their index values.

Results: The index of spleen volume-to-platelet ratio was devised from the derivation cohort. In the validation cohort, the cutoff index value for balanced sensitivity and specificity (> 3.78) resulted in the sensitivity of 69.4% and the specificity of 78.5% for detecting high-risk varix, and the cutoff index value for high sensitivity (> 1.63) detected all high-risk varices. The index stratified all patients into the low (index value ≤ 1.63; n = 118), intermediate (n = 162), and high (index value > 3.78; n = 139) risk groups with cumulative 5-year incidences of varix bleeding of 0%, 1.0%, and 12.0%, respectively (p < .001).

Conclusion: The spleen volume-to-platelet ratio obtained using deep learning-based CT analysis is useful to detect high-risk varices and to assess the risk of varix bleeding.

Key Points: • The criterion of spleen volume to platelet > 1.63 detected all high-risk varices in the validation cohort, while the absence of visible varix did not exclude all high-risk varices. • Visual varix grade ≥ 2 detected high-risk varix with a high specificity (96.5-100%). • Combining spleen volume-to-platelet ratio ≤ 1.63 and visual varix grade of 0 identified low-risk patients who had no high-risk varix and varix bleeding on 5-year follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-020-07430-3DOI Listing
May 2021

Evaluation of immune-biomarker expression in high-grade soft-tissue sarcoma: HLA-DQA1 expression as a prognostic marker.

Exp Ther Med 2020 Nov 18;20(5):107. Epub 2020 Sep 18.

Medical Research Institute, Pusan National University Hospital, Busan 49241, Republic of Korea.

High-grade soft-tissue sarcoma (STS) is a highly malignant neoplasm with a poor overall prognosis. Numerous prognostic factors determine tumor progression and patient outcomes. Various immune-associated cells identified in the tumor microenvironment have important roles in various tumor types. The present study was performed to evaluate the expression of immune-associated genes and to elucidate the association between these genes and the prognosis in high-grade STS. A total of 12 formalin-fixed, paraffin-embedded tissue samples of high-grade STS were subjected to gene expression analysis using the NanoString nCounter System and another 35 samples were used for immunohistochemistry. For comparative analysis, the patients were divided into two groups according to overall survival (OS). The expression levels of 770 genes were first analyzed using the nCounter PanCancer Immune Profiling Panel. Immunohistochemistry was then performed for the most significantly altered genes. Subsequently, the association between gene expression and prognosis of high-grade STS was evaluated. Of the 770 immune-associated genes analyzed, several genes were identified as being differentially expressed between the two groups. Based on gene expression levels and fold change, 13 representative genes were identified; 7 of the 13 candidate genes (C3, CD36, DOCK9, FCER2, FOS, HLA-DRB4 and NCAM1) were significantly overexpressed in the poor prognosis group, while the other 6 immune-associated genes (BIRC5, DUSP4, FOXP3, HLA-DQA1, HLA-DQB1 and LAG3) were increased in the good prognosis group. By immunohistochemistry, the expression of the 13 immune-associated genes was confirmed to be significantly different between the two groups. Expression of HLA-DQA1, HLA-DQB1 and HLA-DRB4 was observed in 74.3, 34.3 and 48.6% of tumors, respectively. HLA-DQA1 and HLA-DQB1 were significantly decreased, whereas HLA-DRB4 was significantly increased in the poor prognosis group. Of note, expression of HLA-DQA1 was associated with a significantly longer OS (P=0.028). In conclusion, HLA-DQA1 expression was significantly associated with long-term survival and may therefore be an immune biomarker for good prognosis in high-grade STS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2020.9225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517476PMC
November 2020

Measuring Chromosome Pairing During Homologous Recombination in Yeast.

Methods Mol Biol 2021 ;2153:253-265

Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.

The precise organization of the genome inside the cell nucleus is vital to many cell functions including gene expression, cell division, and DNA repair. Here we describe a method to measure pairing of DNA loci during homologous recombination (HR) at a site-specific double-strand break (DSB) in Saccharomyces cerevisiae. This method utilizes a chromosome tagging system in diploid yeast cells to visualize both the DNA at the break site and the homologous DNA that serves as a repair template. DNA repair products are confirmed in parallel by genomic blot. This visualization method provides insight into the physical contact that occurs between homologous loci during HR and correlates physical interaction with the timing of DNA repair.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-1-0716-0644-5_18DOI Listing
March 2021

Regorafenib Versus Nivolumab After Sorafenib Failure: Real-World Data in Patients With Hepatocellular Carcinoma.

Hepatol Commun 2020 Jul 16;4(7):1073-1086. Epub 2020 Jun 16.

Department of Gastroenterology Liver Center University of Ulsan College of Medicine Seoul Republic of Korea.

Regorafenib and nivolumab are drugs approved for second-line treatment of patients with hepatocellular carcinoma (HCC) after sorafenib failure. However, the effectiveness of regorafenib and nivolumab following sorafenib has not been directly compared. This study retrospectively evaluated 373 patients with HCC who were treated with regorafenib (n = 223) or nivolumab (n = 150) after sorafenib failure between July 2017 and February 2019. Progression-free survival (PFS; hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.69-1.06;  = 0.150), time to progression (TTP; HR, 0.95; 95% CI, 0.77-1.19; = 0.680), and overall survival (OS; HR, 0.83; 95% CI, 0.64-1.07; = 0.154) did not differ significantly between groups of patients treated with regorafenib and nivolumab, findings consistently observed by multivariable-adjusted, propensity score-matched, and inverse probability treatment weighting (IPTW) analyses. However, the objective response rate was significantly higher in the nivolumab than in the regorafenib group (13.3% vs. 4.0%; = 0.002). When the effectiveness of regorafenib and nivolumab was compared in nonprogressors to treatment, defined as patients who achieved complete response, partial response, or stable disease after first response evaluation, PFS (HR, 0.50; 95% CI, 0.33-0.75; = 0.001), TTP (HR, 0.48; 95% CI, 0.31-0.73; < 0.001), and OS (HR, 0.51; 95% CI, 0.31-0.87; = 0.013) were significantly longer in the 59 nonprogressors to nivolumab than in the 104 nonprogressors to regorafenib, findings also observed by multivariable-adjusted and IPTW analyses. Survival outcomes in patients treated with regorafenib and nivolumab after sorafenib failure did not differ significantly. However, nivolumab may be more effective than regorafenib in nonprogressors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep4.1523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327222PMC
July 2020

US LI-RADS visualization score: diagnostic outcome of ultrasound-guided focal hepatic lesion biopsy in patients at risk for hepatocellular carcinoma.

Ultrasonography 2021 Jan 9;40(1):167-175. Epub 2020 May 9.

Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Purpose: This study investigated the diagnostic outcome of ultrasound (US)-guided focal hepatic lesion biopsy in patients at risk for hepatocellular carcinoma (HCC) and evaluated the US visualization score as a risk factor for non-diagnostic results.

Methods: We retrospectively evaluated 208 focal hepatic lesions in 208 patients who underwent US-guided biopsy in 2016. Using the US Liver Imaging Reporting and Data System version 2017, each exam was assigned a US visualization score (A, B, or C). Final diagnoses were made using pathology reports, and biopsy results were categorized as diagnostic or non-diagnostic. Univariable and multivariable analyses were performed to determine risk factors for non-diagnostic results, including US visualization score and other clinical covariates.

Results: Of the 208 lesions, 85.1% were diagnostic and 14.9% were non-diagnostic. The rates of non-diagnostic results were 8.9%, 25.5%, and 57.1% for scores of A, B, and C, respectively. In the univariable analysis, scores of B or C were associated with a significantly higher rate of nondiagnostic results than scores of A (58.1% vs. 24.9%, P<0.001). In the multivariable analysis, US visualization score of B or C (adjusted odds ratio [aOR], 2.7; P=0.027), high-risk needle pathway usage (aOR, 5.7; P=0.001), and lesion size ≤2.0 cm (aOR, 2.7; P=0.024) were independent risk factors for non-diagnostic results.

Conclusion: US-guided biopsy had a high diagnostic yield for focal hepatic lesions in patients at risk for HCC. US visualization score of B or C, lesion size ≤2.0 cm, and high-risk needle pathway usage were independent risk factors for non-diagnostic results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14366/usg.19066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758094PMC
January 2021

Differences in immune-related gene expressions and tumor-infiltrating lymphocytes according to chemotherapeutic response in ovarian high-grade serous carcinoma.

J Ovarian Res 2020 Jun 8;13(1):65. Epub 2020 Jun 8.

Department of Pathology, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan, 49241, Republic of Korea.

Background: High-grade serous carcinoma (HGSC) of the ovary is the most common subtype of epithelial ovarian cancer (EOC) and has an overall poor prognosis. There is increasing awareness of the importance of immune cell populations and tumor-infiltrating lymphocytes (TILs) in various immune pathways in the tumor microenvironment. The present study evaluated immune-related gene expressions and TIL levels, as well as associated chemotherapeutic responses, to elucidate the correlation between gene expression and TIL levels in HGSC.

Materials And Methods: Fresh tissue samples from 12 HGSC patients were included in this study. Depending on their response to adjuvant chemotherapy, the patients were divided into two groups: chemosensitive (CS) or chemoresistant (CR). The expression levels of 770 genes were analyzed using the nCounter® PanCancer Immune Profiling Panel of the NanoString nCounter® Analysis System. Quantitative real-time polymerase chain reaction (qPCR) was performed to validate the NanoString data obtained. The TIL levels in representative sections were examined via hematoxylin and eosin staining. Gene and TIL levels were subsequently correlated with the chemotherapeutic response.

Results: Several genes were differentially expressed in the two study groups. Eleven representative genes were selected for further evaluation. Of those, 9 genes (IRF1, CXCL9, LTB, CCL5, IL-8, GZMA, PSMB9, CD38, and VCAM1) were significantly overexpressed in the CS group; whereas expressions of 2 genes (CD24 and CD164) were increased in the CR group. Results of qPCR were consistent with those of the NanoString nCounter® analysis. Stromal TIL levels were significantly associated with adjuvant chemotherapeutic response (p = 0.001).

Conclusions: Significant differences between the CS and CR groups were observed in the expression levels of immune-related genes. Immune-related gene expressions were significantly higher in the CS group, which also had higher levels of TILs. We, therefore, suggest that, in patients with HGSC, immune-related gene expressions and TIL levels may be associated with chemotherapeutic sensitivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13048-020-00667-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278194PMC
June 2020

Comparison of the diagnostic performance of imaging criteria for HCCs ≤ 3.0 cm on gadoxetate disodium-enhanced MRI.

Hepatol Int 2020 Jul 20;14(4):534-543. Epub 2020 Apr 20.

Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

Background And Purpose: Imaging-based diagnostic systems play important roles in hepatocellular carcinoma (HCC). We aimed to compare the diagnostic performance of recently updated imaging criteria for HCCs ≤ 3.0 cm on gadoxetate disodium-enhanced magnetic resonance imaging (MRI).

Methods: 493 nodules (399 HCCs, 24 other malignancies, 70 benign) 1.0-3.0 cm from 400 patients, including 322 male (mean age 59.3 ± 9.4 years) and 78 female (mean age 61.2 ± 9.0 years), at risk for HCC who underwent gadoxetate disodium-enhanced MRI between July 2015 and December 2016 were retrospectively evaluated. Final diagnosis was determined histopathologically or clinically. The sensitivity and specificity in diagnosing HCC of the latest versions of four imaging criteria [Liver Imaging Reporting and Data System (LI-RADS), European Association for the Study of the Liver (EASL), Asian Pacific Association for the Study of the Liver (APASL), Korean Liver Cancer Association-National Cancer Center (KLCA-NCC)] were compared using generalized estimating equations.

Results: In 331 only pathologically diagnosed nodules, the sensitivities of both the APASL (86.8%) and KLCA-NCC criteria (85.4%) were significantly higher than the sensitivities of the EASL (71.8%) and LR-5 (71.1%) criteria (p < 0.001 for each pairwise comparison). However, the specificity of LR-5 was significantly higher than that of APASL (92.2% vs. 70.6%, respectively; p = 0.011) but did not differ significantly from the specificities of EASL (84.3%; p = 0.634) and KLCA-NCC (78.4%; p = 0.107).

Conclusion: Of the four international imaging criteria, LI-RADS and EASL showed high specificity but suboptimal sensitivity for diagnosing HCCs ≤ 3 cm. However, APASL and KLCA-NCC had a higher sensitivity but a lower specificity than LI-RADS and EASL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12072-020-10040-2DOI Listing
July 2020

Percutaneous Radiofrequency Ablation for Metachronous Hepatic Metastases after Curative Resection of Pancreatic Adenocarcinoma.

Korean J Radiol 2020 03;21(3):316-324

Department of Radiology and Research Institute of Radiology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Objective: To retrospectively evaluate the safety and efficacy of percutaneous radiofrequency ablation (RFA) in patients with metachronous hepatic metastases arising from pancreatic adenocarcinoma who had previously received curative surgery.

Materials And Methods: Between 2002 and 2017, percutaneous RFA was performed on 94 metachronous hepatic metastases (median diameter, 1.5 cm) arising from pancreatic cancer in 60 patients (mean age, 60.5 years). Patients were included if they had fewer than five metastases, a maximum tumor diameter of ≤ 5 cm, and disease confined to the liver or stable extrahepatic disease. For comparisons during the same period, we included 66 patients who received chemotherapy only and met the same eligibility criteria described.

Results: Technical success was achieved in all hepatic metastasis without any procedure-related mortality. During follow-up, local tumor progression of treated lesions was observed in 38.3% of the tumors. Overall median survival and 3-year survival rates were 12 months and 0%, respectively from initial RFA, and 14.7 months and 2.1%, respectively from the first diagnosis of liver metastasis. Multivariate analysis showed that a large tumor diameter of > 1.5 cm, a late TNM stage (≥ IIB) before curative surgery, a time from surgery to recurrence of < 1 year, and the presence of extrahepatic metastasis, were all prognostic of reduced overall survival after RFA. Median overall (12 months vs. 9.1 months, = 0.094) and progression-free survival (5 months vs. 3.3 months, = 0.068) were higher in the RFA group than in the chemotherapy group with borderline statistical difference.

Conclusion: RFA is safe and may offer successful local tumor control in patients with metachronous hepatic metastases arising from pancreatic adenocarcinoma. Patients with a small diameter tumor, early TNM stage before curative surgery, late hepatic recurrence, and liver-only metastasis benefit most from RFA treatment. RFA provided better survival outcomes than chemotherapy for this specific group with borderline statistical difference.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3348/kjr.2019.0647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039725PMC
March 2020

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

Eur Radiol 2020 May 4;30(5):2881-2889. Epub 2020 Feb 4.

Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea.

Objectives: To determine the strength of association with hepatocellular carcinoma (HCC) of each ancillary feature (AF) in LI-RADS version 2018, and to develop an appropriate strategy for applying AFs to improve the diagnosis of HCC ≤ 3 cm on gadoxetate-enhanced MRI.

Methods: A total of 385 nodules (283 HCCs, 18 non-HCC malignancies, 84 benign nodules) of ≤ 3 cm in 266 patients at risk for HCC who underwent gadoxetate-enhanced MRI in 2016 were retrospectively evaluated. Two radiologists independently evaluated the presence/absence of AFs, and assigned a LI-RADS category to each nodule. Diagnostic odds ratio (DOR) of each AF was assessed. To improve the diagnostic performance for HCC, various criteria were developed based on the number of AFs favoring malignancy in general or HCC in particular. Generalized estimating equation models were used to compare the diagnostic performance of each criterion with that of the major features (MFs) only.

Result: All AFs favoring HCC in particular and malignancy in general were more common in the HCC group than in the non-HCC group. Of these AFs, hepatobiliary-phase hypointensity had the strongest association with HCC (DOR, 21.82; 95% confidence interval, 5.59-85.20). When we applied AFs in addition to MFs, the new criterion (with a number of AFs ≥ 4) had significantly higher sensitivity (80.6% vs. 70.0%; p < 0.001) than MFs only, without significant lower specificity (85.3% vs. 90.2%; p = 0.060).

Conclusions: The AFs varied in the strengths of association with HCC. More strict application of AFs (AFs ≥ 4) in LR-3 may improve the diagnostic performance for probable HCC ≤ 3 cm.

Key Points: • The ancillary features (AFs) in the Liver Imaging Reporting and Data System version 2018 showed variable frequencies of occurrence and strengths of association with hepatocellular carcinoma (HCC). • Of the various AFs, hepatobiliary-phase hypointensity had the highest frequency and strongest association with HCC on gadoxetate disodium-enhanced MRI. • When applying AFs in addition to major features, a criterion of four or more AFs significantly increased the sensitivity for diagnosing HCC, without a significantly decreased specificity, especially in LR-3 observations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-019-06645-3DOI Listing
May 2020

Non-enhanced magnetic resonance imaging as a surveillance tool for hepatocellular carcinoma: Comparison with ultrasound.

J Hepatol 2020 04 10;72(4):718-724. Epub 2019 Dec 10.

Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Background & Aims: Recently revised international guidelines for hepatocellular carcinoma (HCC) suggest that patients with inadequate ultrasonography be assessed by alternative imaging modalities. Non-enhanced MRI has potential as a surveillance tool based on the short scan times required and the absence of contrast agent-associated risks. This study compared the performance of non-enhanced MRI and ultrasonography for HCC surveillance in high-risk patients.

Methods: We included 382 high-risk patients in a prospective cohort who underwent 1 to 3 rounds of paired gadoxetic acid-enhanced MRI and ultrasonography. Non-enhanced MRI, consisting of diffusion-weighted imaging (DWI) and T2-weighted imaging, was simulated and retrospectively analyzed, with results considered positive when lesion(s) ≥1 cm showed diffusion restriction or mild-moderate T2 hyperintensity. Ultrasonography results were retrieved from patient records. HCC was diagnosed histologically and/or radiologically. Sensitivity, positive predictive value (PPV), specificity, and negative predictive value (NPV) were evaluated using generalized estimating equations.

Results: Forty-eight HCCs were diagnosed in 43 patients. Per-lesion and per-exam sensitivities of non-enhanced MRI were 77.1% and 79.1%, respectively, which were higher than those achieved with ultrasonography (25.0% and 27.9%, respectively, p <0.001). Specificities of non-enhanced MRI (97.9%) and ultrasonography (94.5%) differed significantly (p <0.001). NPV was higher for non-enhanced MRI (99.1%) than ultrasonography (96.9%). Per-lesion and per-exam PPVs were higher for non-enhanced MRI (56.9% and 61.8%, respectively) than for ultrasonography (16.7% and 17.7%, respectively). The estimated scan time of non-enhanced MRI was <6 min.

Conclusion: Based on its good performance, short scan times, and the lack of contrast agent-associated risks, non-enhanced MRI is a promising option for HCC surveillance in high-risk patients.

Lay Summary: Recently revised international guidelines for hepatocellular carcinoma (HCC) suggest that selected patients with inadequate surveillance on ultrasonography be assessed by alternative imaging modalities such as computed tomography or magnetic resonance imaging (MRI). Herein, we show that MRI without contrast agents performed significantly better than ultrasonography for HCC surveillance in high-risk patients. Given this good performance, as well as short scan times and the lack of contrast agent-associated risks, non-enhanced MRI is a promising option for HCC surveillance in high-risk patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2019.12.001DOI Listing
April 2020

Feasibility, safety, and adequacy of research biopsies for cancer clinical trials at an academic medical center.

PLoS One 2019 12;14(8):e0221065. Epub 2019 Aug 12.

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Objective: Research biopsies are an essential component of cancer clinical trials for studying drug efficacy and identifying biomarkers. Site-level clinical investigators, however, do not have access to results on the adequacy of research biopsies for histological or molecular assays, because samples are sent to central labs and the test results are seldom reported back to site-level investigators unless requested. We evaluated the feasibility, safety, and adequacy of research biopsies performed at an academic medical center.

Materials And Methods: We retrospectively reviewed the data on 122 research biopsy sessions conducted in 99 patients via percutaneous core needle biopsy for 39 clinical trials from January 2017 to February 2018 at a single institute. We asked the sponsors of each clinical trial for the adequacy of the biopsy samples for histological or molecular assays.

Results: The biopsy success rate was 93.4% (113/122), with nine samples categorized as inadequate for obtaining pathologic diagnosis. Post-biopsy complications occurred in 9.8% (12/122) of biopsies, all of which were mild and completely recovered by the day after the biopsy. The sponsors of clinical trials provided feedbacks on the adequacy of 76 biopsy samples, and noted that a total of 8 biopsy samples from 7 patients were inadequate for analysis, resulting in an adequacy rate of 89.5% (68/76): the reasons for inadequacy were insufficient tumor content for immunohistochemistry (n = 3) and low RNA yield for sequencing (n = 5).

Conclusion: Research biopsies performed at an experienced, multidisciplinary center had acceptable safety for patients as well as practicality in terms of obtaining adequate tissue samples for molecular studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0221065PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690517PMC
March 2020

Correction to: PD-L1 expression on stromal tumor-infiltrating lymphocytes is a favorable prognostic factor in ovarian serous carcinoma.

J Ovarian Res 2019 Jul 23;12(1):68. Epub 2019 Jul 23.

Department of Pathology, Pusan National University Yangsan Hospital, 20, Geumo-ro, Mulguem-eup, Yangsan-si, Gyeongsangnam-do, South Korea.

Following publication of the original article [1], the authors opted to correct the incorrect e-mail address of the corresponding author from [email protected] to [email protected] , grant in the Acknowledgements section and Author details. Below are the updated version of the Acknowledgements and Author details.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13048-019-0540-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647086PMC
July 2019

Contrast-enhanced US with Perfluorobutane for Hepatocellular Carcinoma Surveillance: A Multicenter Diagnostic Trial (SCAN).

Radiology 2019 09 9;292(3):638-646. Epub 2019 Jul 9.

From the Department of Radiology, Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea (J.H.P., S.S.L.); Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea (M.S.P., M.J.P.); Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea (S.J.L., S.H.P.); Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (W.K.J.); Department of Radiology and Institute of Radiation Medicine, Seoul National University Hospital, Seoul, Republic of Korea (J.Y.L.); Department of Radiology, Health Promotion Center, Samsung Medical Center, Seoul, Republic of Korea (M.J.P.); Yonsei Biomedical Research Institute, Department of Radiology, Research Institute of Radiological Science (K.H.) and Department of Preventive Medicine (C.M.N.), Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Radiology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea (K.H.L.); and Program in Biomedical Radiation Sciences, Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Interdisciplinary Program in Bioengineering, Seoul National University, Seoul, Republic of Korea (K.H.L.).

Background US has served as a standard surveillance tool for hepatocellular carcinoma (HCC); however, the detection rate and false referral rate with this modality are suboptimal. Purpose To evaluate the added value of perfluorobutane-enhanced US when combined with conventional B-mode US as an HCC surveillance tool in participants with liver cirrhosis. Materials and Methods This prospective multi-institution diagnostic trial (, NCT02188901) used an intraindividual comparison design in a single arm of study participants and was conducted at five referral hospitals. Eligible participants who had liver cirrhosis related to viral hepatitis and were undergoing US for HCC surveillance were enrolled from October 2014 to August 2016. Immediately after completion of B-mode US but before performance of perfluorobutane-enhanced US, operating radiologists entered the results of B-mode US. After completion of subsequent perfluorobutane-enhanced US (Kupffer phase with or without vascular-phase US), the radiologists recorded the results. The presence of HCC was confirmed either with pathologic analysis or radiologically by using dynamic contrast material-enhanced CT or gadoxetic acid-enhanced MRI. The primary end points were the detection rate of early-stage HCC (Barcelona Clinic Liver Cancer staging system stage 0 or A) and false referral rate. The primary end points were compared in a per-participant manner by using the McNemar test. Results A total of 524 participants (mean age, 54 years ± 9 [standard deviation]) were included. Of these, 493 (94.1%) had liver cirrhosis related to the hepatitis B virus. Ten HCCs were confirmed in eight participants. The detection rate of early-stage HCC was not significantly improved by adding perfluorobutane-enhanced US to conventional B-mode US (difference, 0.4% [95% confidence interval: -0.3%, 1.1%]; = .16). The false referral rate was significantly reduced (difference, -3.2% [95% confidence interval: -5.0%, -1.4%]; < .001). Conclusion The addition of perfluorobutane-enhanced US to conventional B-mode US reduced the false referral rate without a significant improvement in the detection rate of early-stage hepatocellular carcinoma for surveillance in a population in which the hepatitis B virus predominated. © RSNA, 2019
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2019190183DOI Listing
September 2019

Validation of US Liver Imaging Reporting and Data System Version 2017 in Patients at High Risk for Hepatocellular Carcinoma.

Radiology 2019 08 18;292(2):390-397. Epub 2019 Jun 18.

From the Department of Radiology and Research Institute of Radiology (J.H.S., S.H.C., S.Y.K., J.H.B., H.J.W., S.J.L.), and Department of Gastroenterology (Y.S.L.), University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, South Korea; Department of Radiology, National Cancer Center, Goyang, South Korea (H.Y.J.).

Background The 2017 version of the Liver Imaging Reporting and Data System (LI-RADS) recently included standardized interpretation, reporting, and management guidelines for US (US LI-RADS); however, this system has not yet been validated. Purpose To evaluate the diagnostic performance of US LI-RADS version 2017 for detecting hepatocellular carcinoma (HCC) in participants at high risk and to determine the clinical factors associated with a poor visualization score. Materials and Methods This study included 407 prospectively recruited participants (mean age, 56 years; age range, 28-76 years) with cirrhosis at high risk for HCC who underwent US surveillance from November 2011 to August 2012. Two radiologists retrospectively analyzed US images, assigning a LI-RADS category (US-1 = negative, US-2 = subthreshold, US-3 = positive) and a visualization score (A = no or minimal limitations, B = moderate limitations, C = severe limitations). The sensitivity and specificity for diagnosing HCC were calculated on a per-patient and per-lesion basis, using pathologic results and typical CT or MRI as reference standards. The risk factors for a poor visualization score were determined by using univariable and multivariable analyses. Results Of 429 lesions in 407 participants, there were 32 HCCs in 28 participants. In the per-lesion analysis, the specificity for US-3 was 366 of 397 (92%; 95% confidence interval [CI]: 89%, 95%) and the sensitivity was 11 of 32 (34%; 95% CI: 20%, 52%). In the per-patient analysis, the specificity for US-3 was 352 of 379 (93%; 95% CI: 90%, 95%) and the sensitivity was 11 of 28 (39%; 95% CI: 24%, 58%). Visualization score C (114 of 407 [28%] participants) had the highest false-negative rate (six of seven [86%] participants). High body weight (adjusted odds ratio [OR], 2.1 [95% CI: 1.2, 3.6]; = .01), Child-Pugh class B disease (OR, 2.9 [95% CI: 1.7, 4.9]; < .001), and moderate to severe fatty liver (OR, 1.7 [95% CI: 1.0, 2.8]; = .047) were associated with a poor visualization score of C. Conclusion The US-3 category demonstrated high specificity but low sensitivity for diagnosing hepatocellular carcinoma. The visualization score C had a higher false-negative rate than scores A or B, and patients with high body weight, Child-Pugh class B disease, and moderate to severe fatty liver may present limitations for US surveillance. © RSNA, 2019 See also the editorial by Milot in this issue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2019190035DOI Listing
August 2019

PD-L1 expression on stromal tumor-infiltrating lymphocytes is a favorable prognostic factor in ovarian serous carcinoma.

J Ovarian Res 2019 Jun 17;12(1):56. Epub 2019 Jun 17.

Department of Pathology, Pusan National University Yangsan Hospital, 20, Geumo-ro, Mulguem-eup, Yangsan-si, Gyeongsangnam-do, South Korea.

Background: PD-L1 expression levels determined by immunostaining are known to be related to the survival rate and prognosis of patients with various types of cancers, as well as to the therapeutic response to immune checkpoint inhibitors. Recently, the U.S. Food and Drug Administration approved an immune checkpoint inhibitor for the treatment of non-small cell lung cancer along with the clones used for PD-L1 immunostaining to predict the resulting response. In this study, we performed PD-L1 immunostaining of tissue microarrays from ovarian epithelial cancer using SP263, an approved clone, and examined the effect of PD-L1 expression on survival rate and prognosis.

Methods: Tissue microarrays were constructed from ovarian epithelial cancer tissues of 248 patients and PD-L1 immunostaining was performed using the SP263 clone. PD-L1 expression levels in tumor cells, intraepithelial tumor-infiltrating lymphocytes, and stromal tumor-infiltrating lymphocytes were evaluated, and the effect of PD-L1 expression on survival and prognosis was analyzed.

Results: PD-L1 was detected in tumor cells as well as intraepithelial tumor-infiltrating lymphocytes and stromal tumor-infiltrating lymphocytes. It was most frequently expressed in stromal tumor-infiltrating lymphocytes. The Kaplan-Meier curve analysis and log rank test showed that only high stromal PD-L1 expression was associated with increased overall survival in ovarian serous carcinoma. Multivariate and univariate Cox regression analyses revealed that stromal PD-L1 expression was an independent prognostic factor, especially in ovarian serous carcinoma.

Conclusions: PD-L1 immunostaining using SP263 was observed in tumor cells as well as intraepithelial and stromal tumor-infiltrating lymphocytes. PD-L1-expressing stromal tumor-infiltrating lymphocytes were associated with an increased overall survival rate and may serve as a favorable prognostic factor in ovarian cancer, particularly serous carcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13048-019-0526-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580633PMC
June 2019

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

J Hepatol 2019 09 18;71(3):534-542. Epub 2019 May 18.

Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul 05505, Republic of Korea.

Background & Aims: Although gadoxetate disodium-enhanced magnetic resonance imaging (MRI) shows higher sensitivity for diagnosing hepatocellular carcinoma (HCC), its arterial-phase images may be unsatisfactory because of weak arterial enhancement. We investigated the clinical effectiveness of arterial subtraction images from gadoxetate disodium-enhanced MRI for diagnosing early-stage HCC using the Liver Imaging Reporting and Data System (LI-RADS) v2018.

Methods: In 258 patients at risk of HCC who underwent gadoxetate disodium-enhanced MRI in 2016, a total of 372 hepatic nodules (273 HCCs, 18 other malignancies, and 81 benign nodules) of 3.0 cm or smaller were retrospectively analyzed. Final diagnosis was assessed histopathologically or clinically (marginal recurrence after treatment or change in lesion size on follow-up imaging). The detection rate for arterial hyperenhancement was compared between ordinary arterial-phase and arterial subtraction images, and the benefit of arterial subtraction images in diagnosing HCC using LI-RADS was assessed.

Results: Arterial subtraction images had a significantly higher detection rate for arterial hyperenhancement than ordinary arterial-phase images, both for all hepatic nodules (72.3% vs. 62.4%, p <0.001) and HCCs (91.9% vs. 80.6%, p <0.001). Compared with ordinary arterial-phase images, arterial subtraction images significantly increased the sensitivity of LI-RADS category 5 for diagnosis of HCC (64.1% [173/270] vs. 55.9% [151/270], p <0.001), without significantly decreasing specificity (92.9% [91/98] vs. 94.9% [93/98], p = 0.155). For histopathologically confirmed lesions, arterial subtraction images significantly increased sensitivity to 68.8% (128/186) from the 61.3% (114/186) of ordinary arterial-phase images (p <0.001), with a minimal decrease in specificity to 84.8% (39/46) from 89.1% (41/46) (p = 0.151).

Conclusions: Arterial subtraction images of gadoxetate disodium-enhanced MRI can significantly improve the sensitivity of early-stage HCC diagnosis using LI-RADS, without a significant decrease in specificity.

Lay Summary: Gadoxetate disodium-enhanced magnetic resonance imaging is an imaging technique with a high sensitivity for the diagnosis of hepatocellular carcinoma. However, arterial-phase images may be unsatisfactory because of weak arterial enhancement. We found that using arterial subtraction images led to clinically meaningful improvements in the diagnosis of early-stage hepatocellular carcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2019.05.005DOI Listing
September 2019

Stromal tumor-infiltrating lymphocytes evaluated on H&E-stained slides are an independent prognostic factor in epithelial ovarian cancer and ovarian serous carcinoma.

Oncol Lett 2019 May 1;17(5):4557-4565. Epub 2019 Mar 1.

Department of Pathology, Pusan National University Hospital, Seo-Gu, Busan 602-739, Republic of Korea.

Studies on tumor-infiltrating lymphocytes (TILs) in epithelial ovarian cancer (EOC) have focused on the clinical significance of inflammatory cells of specific subtypes that are identifiable using immunohistochemistry. However, the subtypes of inflammatory cells that reportedly affect patient survival and prognosis have differed from study to study, and few studies have examined TILs using hematoxylin and eosin (H&E) staining. Therefore, the present study aimed to identify the clinical importance of general stromal TILs in EOC by using H&E staining to apply breast cancer recommendations from the International TILs Working Group 2014 on breast cancer using H&E staining. Stromal TILs in 256 EOC cases from Pusan National University Hospital and 475 cases of high-grade serous carcinoma from The Cancer Genome Atlas dataset were assessed. Stromal TILs were evaluated using H&E-stained slides according to the breast cancer recommendations of the International Working Group 2014, and patients were classified into low and high stromal TIL groups according to their stromal TIL values. The associations of these groups with clinicopathologic factors were assessed, and it was confirmed that group membership correlated with survival and prognosis. According to the χ assessment, the stromal TIL group was associated with tumor grade. Furthermore, the stromal TIL group was associated with overall survival according to Kaplan-Meier analysis with the log-rank test. Finally, the stromal TIL group was an independent prognostic factor according to univariate and multivariate Cox regression analyses. In cases of EOC, the evaluation of general stromal TILs on H&E-stained slides could be used to predict prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ol.2019.10095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444488PMC
May 2019

Diagnostic performance of [F]FDG-PET/MRI for liver metastasis in patients with primary malignancy: a systematic review and meta-analysis.

Eur Radiol 2019 Jul 4;29(7):3553-3563. Epub 2019 Feb 4.

Department of Radiology and the Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, South Korea.

Objectives: To systematically determine the diagnostic accuracy of 18-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging ([F]FDG-PET/MRI) for the detection of liver metastases and evaluate the sources of heterogeneity in the reported results.

Methods: PubMed and EMBASE databases were searched up until December 31, 2017, to identify original research studies reporting the diagnostic performance (Se and Sp) of PET/MRI for liver metastases, in comparison with PET/CT. Study quality was assessed using QUADAS-2. The summary Se and Sp of the studies were estimated using hierarchical modeling methods. To determine causes of study heterogeneity, the presence of a threshold effect was analyzed, and meta-regression analysis was performed.

Results: Of 546 articles screened, eight suitable articles were identified, with seven for per-lesion analysis, and four for per-patient analysis. The meta-analytic summary Se and Sp for per-patient-based analysis were 99.2% (95% CI, 31.4-100.0%, I = 89.4%) and 98.6% (95% CI, 84.0-99.9%, I = 0.0%), respectively, while for per-lesion-based analysis they were 95.4% (95% CI, 78.3-99.2%, I = 99.7%) and 99.3% (95% CI, 93.8-99.9%, I = 96.5%). PET/MRI showed higher Se (95.4% vs. 68.3%) and Sp (99.3% vs. 95.8%) than PET/CT. Meta-regression analysis showed five significant factors affecting study heterogeneity: study subject characteristics, study design, MRI technique (DWI, HBP after injection of liver-specific contrast media), imaging review method, and reference standard.

Conclusion: The diagnostic accuracy of [F]FDG-PET/MRI for liver metastasis was high overall, but substantial heterogeneity was found. Further randomized controlled studies or prospective studies are needed to investigate the role of PET/MRI in liver metastasis in comparison with PET/CT.

Key Points: • [ F]FDG-PET/MRI has high meta-analytic Se and Sp for the diagnosis of liver metastasis. • PET/MRI using DWI and HBP images significantly increased diagnostic accuracy. • Study heterogeneity was associated with subject characteristics, study design, MRI technique, image review method, and reference standard.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-018-5909-xDOI Listing
July 2019

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

Radiology 2019 02 4;290(2):380-387. Epub 2018 Dec 4.

From the Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea.

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

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2018181197DOI Listing
February 2019
-->