Comparison Between Contrast-Enhanced Computed Tomography and Contrast-Enhanced Magnetic Resonance Imaging With Magnetic Resonance Cholangiopancreatography for Resectability Assessment in Extrahepatic Cholangiocarcinoma

Objective@#To compare the diagnostic performance and interobserver agreement between contrast-enhanced computed tomography (CECT) and contrast-enhanced magnetic resonance imaging (CE-MRI) with magnetic resonance cholangiopancreatography (MRCP) for evaluating the resectability in patients with extrahepatic cholangiocarcinoma (eCCA). @*Materials and Methods@#This retrospective study included treatment-naïve patients with pathologically confirmed eCCA, who underwent both CECT and CE-MRI with MRCP using extracellular contrast media between January 2015 and December 2020.Among the 214 patients (146 males; mean age ± standard deviation, 68 ± 9 years) included, 121 (56.5%) had perihilar cholangiocarcinoma. R0 resection was achieved in 108 of the 153 (70.6%) patients who underwent curative-intent surgery. Four fellowship-trained radiologists independently reviewed the findings of both CECT and CE-MRI with MRCP to assess the local tumor extent and distant metastasis for determining resectability. The pooled area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of CECT and CE-MRI with MRCP were compared using clinical, surgical, and pathological findings as reference standards. The interobserver agreement of resectability was evaluated using Fleiss kappa (κ). @*Results@#No significant differences were observed between CECT and CE-MRI with MRCP in the pooled AUC (0.753 vs. 0.767), sensitivity (84.7% [366/432] vs. 90.3% [390/432]), and specificity (52.6% [223/424] vs. 51.4% [218/424]) (P > 0.05 for all).The AUC for determining resectability was higher when CECT and CE-MRI with MRCP were reviewed together than when CECT was reviewed alone in patients with discrepancies between the imaging modalities or with indeterminate resectability (0.798 [0.754–0.841] vs. 0.753 [0.697–0.808], P = 0.014). The interobserver agreement for overall resectability was fair for both CECT (κ = 0.323) and CE-MRI with MRCP (κ = 0.320), without a significant difference (P = 0.884). @*Conclusion@#CECT and CE-MRI with MRCP showed no significant differences in the diagnostic performance and interobserver agreement in determining the resectability in patients with eCCA.

Contrast-Enhanced CT and Ultrasonography Features of Intracholecystic Papillary Neoplasm with or without associated Invasive Carcinoma

Objective@#To assess the contrast-enhanced CT and ultrasonography (US) findings of intracholecystic papillary neoplasm (ICPN) and determine the imaging features predicting ICPN associated with invasive carcinoma (ICPN-IC). @*Materials and Methods@#In this retrospective study, we enrolled 119 consecutive patients, including 60 male and 59 female, with a mean age ± standard deviation of 63.3 ± 12.1 years, who had pathologically confirmed ICPN (low-grade dysplasia [DP] = 34, high-grade DP = 35, IC = 50) and underwent preoperative CT or US. Two radiologists independently assessed the CT and US findings, focusing on wall and polypoid lesion characteristics. The likelihood of ICPN-IC was graded on a 5-point scale. Univariable and multivariable logistic regression analyses were performed to identify significant predictors of ICPN-IC separately for wall and polypoid lesion findings. The performances of CT and US in distinguishing ICPN-IC from ICPN with dysplasia (ICPN-DP) was evaluated using the area under the receiver operating characteristic curve (AUC). @*Results@#For wall characteristics, the maximum wall thickness (adjusted odds ratio [aOR] = 1.4; 95% confidence interval [CI]: 1.1–1.9) and mucosal discontinuity (aOR = 5.6; 95% CI: 1.3–23.4) on CT were independently associated with ICPN-IC.Among 119 ICPNs, 110 (92.4%) showed polypoid lesions. Regarding polypoid lesion findings, multiplicity (aOR = 4.0; 95% CI: 1.6–10.4), lesion base wall thickening (aOR = 6.0; 95% CI: 2.3–15.8) on CT, and polyp size (aOR = 1.1; 95% CI: 1.0–1.2) on US were independently associated with ICPN-IC. CT showed a higher diagnostic performance than US in predicting ICPN-IC (AUC = 0.793 vs. 0.676; p = 0.002). @*Conclusion@#ICPN showed polypoid lesions and/or wall thickening on CT or US. A thick wall, multiplicity, presence of wall thickening in the polypoid lesion base, and large polyp size are imaging findings independently associated with invasive cancer and may be useful for differentiating ICPN-IC from ICPN-DP

Diagnostic criteria of perfluorobutane-enhanced ultrasonography for diagnosing hepatocellular carcinoma in high-risk individuals: how is late washout determined?

Purpose@#The aim of this study was to investigate the optimal washout criteria of perfluorobutane-enhanced ultrasonography (PFB-US) for the diagnosis of hepatocellular carcinoma (HCC) in high-risk individuals. @*Methods@#Participants at risk of HCC with treatment-naïve solid hepatic observations (≥1 cm) who underwent PFB-US from March 2019 to September 2020 were prospectively recruited. Arterial phase hyperenhancement (APHE), washout time, and washout degree were evaluated. The diagnosis of HCC was made by non-rim APHE with late and mild washout. The per-lesion diagnostic performance for diagnosing HCC using different cutoffs for late washout (50, 55, 60, 65, and 70 seconds postcontrast) and the different time windows for determining washout (until 2, 3, 4, 5, 6, 7, 8, 9, and 10 minutes postcontrast) were compared using the McNemar test. @*Results@#In total, 101 participants with 113 observations (mean size, 33.5±2.8 mm; HCCs [n=82], non-HCC malignancies [n=16], benign [n=15]) were evaluated. Non-rim APHE was observed in 86.6% (71/82) of HCCs. As the cutoff time for late washout increased, the specificity increased to 100% (95% confidence interval [CI], 88.8% to 100%) at the 60-second cutoff with 62.2% sensitivity (95% CI, 50.8% to 72.7%). When the time window for determining washout became wider, the sensitivity and accuracy increased until 6 minutes, with 100% specificity at all times. @*Conclusion@#Determining washout within 6 minutes after contrast injection with a 60-second cutoff for late washout showed the highest sensitivity without losing specificity for diagnosing HCC using PFB-US in individuals at high risk.

Diagnostic Performance of 2018 KLCA-NCC Practice Guideline for Hepatocellular Carcinoma on Gadoxetic Acid-Enhanced MRI in Patients with Chronic Hepatitis B or Cirrhosis: Comparison with LI-RADS Version 2018

Objective@#To evaluate the performance of the 2018 Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) Practice Guidelines (hereafter, PG) for the diagnosis of hepatocellular carcinoma (HCC) using gadoxetic acid-enhanced MRI, compared to the Liver Imaging-Reporting and Data System (LI-RADS) version 2018 (hereafter, v2018). @*Materials and Methods@#From January 2013 to October 2015, treatment-naïve hepatic lesions (≥ 1 cm) on gadoxetic acidenhanced MRI in consecutive patients with chronic hepatitis B or cirrhosis were retrospectively evaluated. For each lesion, three radiologists independently analyzed the imaging features and classified the lesions into categories according to the 2018 KLCA-NCC PG and LI-RADS v2018. The imaging features and categories were determined by consensus. Generalized estimating equation (GEE) models were used to compare the per-lesion diagnostic performance of the 2018 KLCA-NCC PG and LI-RADS v2018 using the consensus data. @*Results@#In total, 422 lesions (234 HCCs, 45 non-HCC malignancies, and 143 benign lesions) from 387 patients (79% male; mean age, 59 years) were included. In all lesions, the definite HCC (2018 KLCA-NCC PG) had a higher sensitivity and lower specificity than LR-5 (LI-RADS v2018) (87.2% [204/234] vs. 80.8% [189/234], p < 0.001; 86.2% [162/188] vs. 91.0% [171/188], p = 0.002). However, in lesions of size ≥ 2 cm, the definite HCC had a higher sensitivity than the LR-5 (86.8% [164/189] vs. 82.0 (155/189), p = 0.002) without a reduction in the specificity (80.0% [48/60] vs. 83.3% [50/60], p = 0.15).In all lesions, the sensitivity and specificity of the definite/probable HCC (2018 KLCA-NCC PG) and LR-5/4 did not differ significantly (89.7% [210/234] vs. 91.5% [214/234], p = 0.204; 83.5% [157/188] vs. 79.3% [149/188], p = 0.071). @*Conclusion@#For the diagnosis of HCC of size ≥ 2 cm, the definite HCC (2018 KLCA-NCC PG) had a higher sensitivity than LR-5, without a reduction in specificity. The definite/probable HCC (2018 KLCA-NCC PG) had a similar sensitivity and specificity to that those of the LR-5/4.

Diagnostic Performance of 2018 KLCA-NCC Practice Guideline for Hepatocellular Carcinoma on Gadoxetic Acid-Enhanced MRI in Patients with Chronic Hepatitis B or Cirrhosis: Comparison with LI-RADS Version 2018

Objective@#To evaluate the performance of the 2018 Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) Practice Guidelines (hereafter, PG) for the diagnosis of hepatocellular carcinoma (HCC) using gadoxetic acid-enhanced MRI, compared to the Liver Imaging-Reporting and Data System (LI-RADS) version 2018 (hereafter, v2018). @*Materials and Methods@#From January 2013 to October 2015, treatment-naïve hepatic lesions (≥ 1 cm) on gadoxetic acidenhanced MRI in consecutive patients with chronic hepatitis B or cirrhosis were retrospectively evaluated. For each lesion, three radiologists independently analyzed the imaging features and classified the lesions into categories according to the 2018 KLCA-NCC PG and LI-RADS v2018. The imaging features and categories were determined by consensus. Generalized estimating equation (GEE) models were used to compare the per-lesion diagnostic performance of the 2018 KLCA-NCC PG and LI-RADS v2018 using the consensus data. @*Results@#In total, 422 lesions (234 HCCs, 45 non-HCC malignancies, and 143 benign lesions) from 387 patients (79% male; mean age, 59 years) were included. In all lesions, the definite HCC (2018 KLCA-NCC PG) had a higher sensitivity and lower specificity than LR-5 (LI-RADS v2018) (87.2% [204/234] vs. 80.8% [189/234], p < 0.001; 86.2% [162/188] vs. 91.0% [171/188], p = 0.002). However, in lesions of size ≥ 2 cm, the definite HCC had a higher sensitivity than the LR-5 (86.8% [164/189] vs. 82.0 (155/189), p = 0.002) without a reduction in the specificity (80.0% [48/60] vs. 83.3% [50/60], p = 0.15).In all lesions, the sensitivity and specificity of the definite/probable HCC (2018 KLCA-NCC PG) and LR-5/4 did not differ significantly (89.7% [210/234] vs. 91.5% [214/234], p = 0.204; 83.5% [157/188] vs. 79.3% [149/188], p = 0.071). @*Conclusion@#For the diagnosis of HCC of size ≥ 2 cm, the definite HCC (2018 KLCA-NCC PG) had a higher sensitivity than LR-5, without a reduction in specificity. The definite/probable HCC (2018 KLCA-NCC PG) had a similar sensitivity and specificity to that those of the LR-5/4.

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

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%, p = 0.06 by EASL; 86.1%, p < 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, p < 0.01; 86.1% vs. 91.1% by KCLA-NCC, p = 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.

Ultrasound-guided transient elastography and two-dimensional shear wave elastography for assessment of liver fibrosis: emphasis on technical success and reliable measurements

Purpose@#This study investigated whether the use of ultrasound (US) guidance in transient elastography (TE) improved the technical success and reliability of liver stiffness (LS) measurements and whether 2-dimensional (2D) shear wave elastography (SWE) provided reliable LS measurements if TE measurements failed. @*Methods@#In this prospective study, 292 participants (male:female, 189:103; median age, 60 years) with chronic liver disease (CLD) were enrolled. LS was measured via the consecutive use of conventional TE, 2D-SWE, and US-guided TE. The technical success rates and reliable LS measurement rates of the three elastography techniques were compared. The risk factors for TE failure were assessed through univariate and multivariate logistic regression models. @*Results@#US-guided TE was associated with a higher technical success rate (281 of 292, 96.2%) and a higher reliable measurement rate (266 of 292, 91.1%) than conventional TE (technical success: 256 of 292, 87.7%; reliable measurements: 231 of 292, 79.1%; P<0.001 for both). In participants for whom conventional TE failed, 2D-SWE provided high rates of technical success (36 of 36, 100%) and reliable measurements (30 of 36, 83.3%). TE failure was associated with female sex (odds ratio [OR], 5.85; 95% confidence interval [CI], 1.30 to 26.40), severe reverberation artifacts (OR, 8.79; 95% CI, 3.93 to 19.69), and high skin-to-liver capsule depth (OR, 1.23; 95% CI, 1.09 to 1.39). @*Conclusion@#US guidance in TE improved the technical success and reliable measurement rates in the assessment of LS in patients with CLD. In participants for whom TE failed, subsequent 2D-SWE successfully delivered reliable LS measurements.

Reproducibility of ultrasound attenuation imaging for the noninvasive evaluation of hepatic steatosis

Purpose@#The purpose of this study was to evaluate the intra-observer reproducibility of ultrasound attenuation imaging (ATI) for the noninvasive assessment of hepatic steatosis in patients with suspected hepatic steatosis and the inter-observer reproducibility in asymptomatic volunteers. @*Methods@#This prospective study was approved by our institutional review board and informed consent was obtained from all patients. In group 1, composed of patients with suspected hepatic steatosis (n=143), one abdominal radiologist performed gray-scale ultrasonography and two sessions of ATI. In group 2, composed of healthy volunteers (n=18), three independent sessions of ATI were performed by three abdominal radiologists. The visual degree of hepatic steatosis in all study subjects was graded on a 4-point scale by two independent reviewers using gray-scale ultrasonography. Thereafter, the attenuation coefficient (AC) was correlated with the degree of hepatic steatosis using Spearman rank correlation analysis. Intra-class correlation coefficients (ICCs) were used to assess the intra-observer (group 1) and inter-observer reproducibility (group 2) of ATI measurements. @*Results@#For the intra-observer reproducibility of ATI, the ICC was 0.929 (95% confidence interval [CI], 0.901 to 0.949), and the coefficient of variation was 7.1%. Inter-observer reproducibility of ATI measurements showed an ICC of 0.792 (95% CI, 0.549 to 0.916). The AC showed a significant correlation with the visual grade of hepatic steatosis for both reviewers (rho, 0.780 and 0.695; P<0.001, respectively). @*Conclusion@#ATI showed high intra- and inter-observer reproducibility in the assessment of hepatic steatosis.

Diagnosis and Surveillance of Incidental Pancreatic Cystic Lesions: 2017 Consensus Recommendations of the Korean Society of Abdominal Radiology

The occurrence of incidentally detected pancreatic cystic lesions (PCLs) is continuously increasing. Radiologic examinations including computed tomography and magnetic resonance imaging with magnetic resonance cholangiopancreatography have been widely used as the main diagnostic and surveillance methods for patients with incidental PCLs. Although most incidentally detected PCLs are considered benign, they have the potential to become malignant. Currently, we have several guidelines for the management of incidental PCLs. However, there is still debate over proper management, in terms of accurate diagnosis, optimal follow-up interval, and imaging tools. Because imaging studies play a crucial role in the management of incidental PCLs, the 2017 consensus recommendations of the Korean Society of Abdominal Radiology for the diagnosis and surveillance of incidental PCLs approved 11 out of 16 recommendations. Although several challenges remain in terms of optimization and standardization, these consensus recommendations might serve as useful tools to provide a more standardized approach and to optimize care of patients with incidental PCLs.

High Acceleration Three-Dimensional T1-Weighted Dual Echo Dixon Hepatobiliary Phase Imaging Using Compressed Sensing-Sensitivity Encoding: Comparison of Image Quality and Solid Lesion Detectability with the Standard T1-Weighted Sequence

OBJECTIVE: To compare a high acceleration three-dimensional (3D) T1-weighted gradient-recalled-echo (GRE) sequence using the combined compressed sensing (CS)-sensitivity encoding (SENSE) method with a conventional 3D GRE sequence using SENSE, with respect to image quality and detectability of solid focal liver lesions (FLLs) in the hepatobiliary phase (HBP) of gadoxetic acid-enhanced liver MRI. MATERIALS AND METHODS: A total of 217 patients with gadoxetic acid-enhanced liver MRI at 3T (54 in the preliminary study and 163 in the main study) were retrospectively included. In the main study, HBP imaging was done twice using the standard mDixon-3D-GRE technique with SENSE (acceleration factor [AF]: 2.8, standard mDixon-GRE) and the high acceleration mDixon-3D GRE technique using the combined CS-SENSE technique (CS-SENSE mDixon-GRE). Two abdominal radiologists assessed the two MRI data sets for image quality in consensus. Three other abdominal radiologists independently assessed the diagnostic performance of each data set and its ability to detect solid FLLs in 117 patients with 193 solid nodules and compared them using jackknife alternative free-response receiver operating characteristics (JAFROC). RESULTS: There was no significant difference in the overall image quality. CS-SENSE mDixon-GRE showed higher image noise, but lesser motion artifact levels compared with the standard mDixon-GRE (all p < 0.05). In terms of lesion detection, reader-averaged figures-of-merit estimated with JAFROC was 0.918 for standard mDixon-GRE, and 0.953 for CS-SENSE mDixon-GRE (p = 0.142). The non-inferiority of CS-SENSE mDixon-GRE over standard mDixon-GRE was confirmed (difference: 0.064 [−0.012, 0.081]). CONCLUSION: The CS-SENSE mDixon-GRE HBP sequence provided comparable overall image quality and non-inferior solid FFL detectability compared with the standard mDixon-GRE sequence, with reduced acquisition time.

Microvascular Flow Imaging of Residual or Recurrent Hepatocellular Carcinoma after Transarterial Chemoembolization: Comparison with Color/Power Doppler Imaging

OBJECTIVE: To determine the feasibility of microvascular flow imaging (MVFI) in comparison with color/power Doppler imaging (CDI/PDI) for detection of intratumoral vascularity in suspected post-transarterial chemoembolization (TACE) residual or recurrent hepatocellular carcinomas (HCCs) by using contrast-enhanced ultrasonography (CEUS) or hepatic angiography (HA) findings as the reference standard. MATERIALS AND METHODS: One hundred HCCs (mean size, 2.2 cm) in 100 patients treated with TACE were included in this prospective study. CDI, PDI, and MVFI were performed in tandem for evaluating intratumoral vascularity of the lesions by using an RS85 ultrasound scanner (Samsung Medison Co., Ltd.). Intratumoral vascularity in each technique was assessed by two radiologists in consensus by using a 5-point scale. Then, one of the two radiologists and another radiologist performed additional image review in the reverse order (MVFI-PDI-CDI) for evaluation of intra- and interobserver agreements. Results were then compared with those of either HA or CEUS as the reference. The McNemar test, logistic regression analysis, and intraclass correlation coefficient (ICC) were used. RESULTS: CEUS or HA revealed intratumoral vascularity in 87% (87/100) of the tumors. Sensitivity (79.3%, 69/87) and accuracy (80.0%, 80/100) of MVFI were significantly higher than those of CDI (sensitivity, 27.6% [24/87]; accuracy, 37.0% [37/100]) or PDI (sensitivity, 36.8% [32/87]; accuracy, 44.0% [44/100]) (all p 0.9) and good interobserver agreements (ICCs > 0.6). CONCLUSION: MVFI demonstrated significantly higher sensitivity and accuracy than did CDI and PDI for the detection of intratumoral vascularity in suspected residual or recurrent HCCs after TACE.

Prospective Validation of Intra- and Interobserver Reproducibility of a New Point Shear Wave Elastographic Technique for Assessing Liver Stiffness in Patients with Chronic Liver Disease

OBJECTIVE: To assess intra- and inter-observer reproducibility of a new point shear wave elastography technique (pSWE, S-Shearwave, Samsung Medison) and compare its accuracy in assessing liver stiffness (LS) with an established pSWE technique (Virtual Touch Quantification, VTQ). MATERIALS AND METHODS: Thirty-three patients were enrolled in this Institutional Review Board-approved prospective study. LS values were measured by VTQ on an Acuson S2000 system (Siemens Healthineer) and S-Shearwave on an RS-80A (Samsung Medison) in the same session, followed by two further S-Shearwave sessions for inter- and intra-observer variation at 8-hour intervals. The technical success rate (SR) and reliability of the measurements of both pSWE techniques were compared. The intra- and inter-observer reproducibility of S-Shearwave was determined by intraclass correlation coefficients (ICCs). LS values were measured by both methods of pSWE. The diagnostic performance in severe fibrosis (F ≥ 3) and cirrhosis (F = 4) was evaluated using the receiver operating characteristics curve analysis and the Obuchowski measure with the LS values of transient elastography as the referenced standard. RESULTS: The VTQ (100%, 33/33) and S-Shearwave (96.9%, 32/33) techniques did not display a significant difference in technical SR (p = 0.63) or reliability of LS measurements (96.9%, 32/33; 93.9%, 30/32, respectively, p = 0.61). The inter- and intra-observer agreement for LS measurements using the S-Shearwave technique was excellent (ICC = 0.98 and 0.99, respectively). The mean LS values of both pSWE techniques were not significantly different and exhibited a good correlation (r = 0.78). To detect F ≥ 3 and F = 4, VTQ and S-Shearwave showed comparable diagnostic accuracy as indicated by the following outcomes: areas under receiver operating characteristics curve (AUROC) = 0.87 (95% confidence intervals [CI] 0.70–0.96), 0.89 for VTQ (95% CI 0.74–0.97), respectively; and AUROC = 0.84 (95% CI 0.67–0.94), 0.94 (95% CI 0.80–0.99) for S-Shearwave (p > 0.48), respectively. The Obuchowski measures were similarly high for S-Shearwave and VTQ (0.94 vs. 0.95). CONCLUSION: S-Shearwave shows excellent inter- and intra-observer agreement and diagnostic effectiveness comparable to VTQ in detecting LS.

T₂* Mapping from Multi-Echo Dixon Sequence on Gadoxetic Acid-Enhanced Magnetic Resonance Imaging for the Hepatic Fat Quantification: Can It Be Used for Hepatic Function Assessment?

OBJECTIVE: To evaluate the diagnostic value of T₂* mapping using 3D multi-echo Dixon gradient echo acquisition on gadoxetic acid-enhanced liver magnetic resonance imaging (MRI) as a tool to evaluate hepatic function. MATERIALS AND METHODS: This retrospective study was approved by the IRB and the requirement of informed consent was waived. 242 patients who underwent liver MRIs, including 3D multi-echo Dixon fast gradient-recalled echo (GRE) sequence at 3T, before and after administration of gadoxetic acid, were included. Based on clinico-laboratory manifestation, the patients were classified as having normal liver function (NLF, n = 50), mild liver damage (MLD, n = 143), or severe liver damage (SLD, n = 30). The 3D multi-echo Dixon GRE sequence was obtained before, and 10 minutes after, gadoxetic acid administration. Pre- and post-contrast T₂* values, as well as T₂* reduction rates, were measured from T₂* maps, and compared among the three groups. RESULTS: There was a significant difference in T₂* reduction rates between the NLF and SLD groups (−0.2 ± 4.9% vs. 5.0 ± 6.9%, p = 0.002), and between the MLD and SLD groups (3.2 ± 6.0% vs. 5.0 ± 6.9%, p = 0.003). However, there was no significant difference in both the pre- and post-contrast T₂* values among different liver function groups (p = 0.735 and 0.131, respectively). A receiver operating characteristic (ROC) curve analysis showed that the area under the ROC curve for using T₂* reduction rates to differentiate the SLD group from the NLF group was 0.74 (95% confidence interval: 0.63–0.83). CONCLUSION: Incorporation of T₂* mapping using 3D multi-echo Dixon GRE sequence in gadoxetic acid-enhanced liver MRI protocol may provide supplemental information for liver function deterioration in patients with SLD.

Fucoidan promotes osteoblast differentiation via JNK- and ERK-dependent BMP2-Smad 1/5/8 signaling in human mesenchymal stem cells

Fucoidan has attracted attention as a potential drug because of its biological activities, which include osteogenesis. However, the molecular mechanisms involved in the osteogenic activity of fucoidan in human alveolar bone marrow-derived mesenchymal stem cells (hABM-MSCs) remain largely unknown. We investigated the action of fucoidan on osteoblast differentiation in hABM-MSCs and its impact on signaling pathways. Its effect on proliferation was determined using the crystal violet staining assay. Osteoblast differentiation was evaluated based on alkaline phosphatase (ALP) activity and the mRNA expression of multiple osteoblast markers. Calcium accumulation was determined by Alizarin red S staining. We found that fucoidan induced hABM-MSC proliferation. It also significantly increased ALP activity, calcium accumulation and the expression of osteoblast-specific genes, such as ALP, runt-related transcription factor 2, type I collagen-alpha 1 and osteocalcin. Moreover, fucoidan induced the expression of bone morphogenetic protein 2 (BMP2) and stimulated the activation of extracellular signal-related kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase by increasing phosphorylation. However, the effect of fucoidan on osteogenic differentiation was inhibited by specific inhibitors of ERK (PD98059) and JNK (SP600125) but not p38 (SB203580). Fucoidan enhanced BMP2 expression and Smad 1/5/8, ERK and JNK phosphorylation. Moreover, the effect of fucoidan on osteoblast differentiation was diminished by BMP2 knockdown. These results indicate that fucoidan induces osteoblast differentiation through BMP2-Smad 1/5/8 signaling by activating ERK and JNK, elucidating the molecular basis of the osteogenic effects of fucoidan in hABM-MSCs.

beta-TrCP1 degradation is a novel action mechanism of PI3K/mTOR inhibitors in triple-negative breast cancer cells

An F-box protein, beta-TrCP recognizes substrate proteins and destabilizes them through ubiquitin-dependent proteolysis. It regulates the stability of diverse proteins and functions as either a tumor suppressor or an oncogene. Although the regulation by beta-TrCP has been widely studied, the regulation of beta-TrCP itself is not well understood yet. In this study, we found that the level of beta-TrCP1 is downregulated by various protein kinase inhibitors in triple-negative breast cancer (TNBC) cells. A PI3K/mTOR inhibitor PI-103 reduced the level of beta-TrCP1 in a wide range of TNBC cells in a proteasome-dependent manner. Concomitantly, the levels of c-Myc and cyclin E were also downregulated by PI-103. PI-103 reduced the phosphorylation of beta-TrCP1 prior to its degradation. In addition, knockdown of beta-TrCP1 inhibited the proliferation of TNBC cells. We further identified that pharmacological inhibition of mTORC2 was sufficient to reduce the beta-TrCP1 and c-Myc levels. These results suggest that mTORC2 regulates the stability of beta-TrCP1 in TNBC cells and targeting beta-TrCP1 is a potential approach to treat human TNBC.

Does Establishing a Safety Margin Reduce Local Recurrence in Subsegmental Transarterial Chemoembolization for Small Nodular Hepatocellular Carcinomas?

OBJECTIVE: To test the hypothesis that a safety margin may affect local tumor recurrence (LTR) in subsegmental chemoembolization. MATERIALS AND METHODS: In 101 patients with 128 hepatocellular carcinoma (HCC) nodules (1-3 cm in size and < or = 3 in number), cone-beam CT-assisted subsegmental lipiodol chemoembolization was performed. Immediately thereafter, a non-contrast thin-section CT image was obtained to evaluate the presence or absence of intra-tumoral lipiodol uptake defect and safety margin. The effect of lipiodol uptake defect and safety margin on LTR was evaluated. Univariate and multivariate analyses were performed to indentify determinant factors of LTR. RESULTS: Of the 128 HCC nodules in 101 patients, 49 (38.3%) nodules in 40 patients showed LTR during follow-up period (median, 34.1 months). Cumulative 1- and 2-year LTR rates of nodules with lipiodol uptake defect (n = 27) and those without defect (n = 101) were 58.1% vs. 10.1% and 72.1% vs. 19.5%, respectively (p < 0.001). Among the 101 nodules without a defect, the 1- and 2-year cumulative LTR rates for nodules with complete safety margin (n = 52) and those with incomplete safety margin (n = 49) were 9.8% vs. 12.8% and 18.9% vs. 19.0% (p = 0.912). In multivariate analyses, ascites (p = 0.035), indistinct tumor margin on cone-beam CT (p = 0.039), heterogeneous lipiodol uptake (p = 0.023), and intra-tumoral lipiodol uptake defect (p < 0.001) were determinant factors of higher LTR. CONCLUSION: In lipiodol chemoembolization, the safety margin in completely lipiodolized nodule without defect will not affect LTR in small nodular HCCs.

Effects of low-dose niacin on dyslipidemia and serum phosphorus in patients with chronic kidney disease

BACKGROUND: Niacin supplementation improves dyslipidemia and lowers serum phosphorus levels in patients with chronic kidney disease (CKD). We evaluated whether low-dose niacin supplementation can improve dyslipidemia, lower serum phosphorus levels, and be administered with a low frequency of adverse effects in patients with CKD. METHODS: We retrospectively analyzed the clinical records of patients with CKD who had taken niacin from January 2009 to June 2011. We excluded patients with CKD stage 1 and 5. We then enrolled 31 patients with CKD who had taken niacin at a fixed dose of 500mg/day for 6 months. We also randomly selected 30 patients with CKD who had been taking statin for 9 months as a control group. RESULTS: Among the 34 patients with CKD who were prescribed niacin, five (14%) complained of adverse effects, and three (8%) discontinued niacin. The proportion of patients in the niacin group who had been taking a statin or omega-3 fatty acids was 67.7% and 48.8%, respectively. In the niacin group, high-density lipoprotein cholesterol level was significantly increased and triglyceride level was significantly decreased at 12 and 24 weeks compared with baseline levels (P < 0.05). In the niacin group, phosphorous level (P < 0.05) was significantly decreased, and glomerular filtration rate (GFR) was significantly increased (P < 0.05) at 24 weeks compared with baseline values. CONCLUSION: Low-dose niacin had a low frequency of adverse effects and also improved dyslipidemia, lowered serum phosphorus level, and increased GFR in patients with CKD. Further studies are needed to evaluate the long-term effects of low-dose niacin for renal progression of CKD.

Effects of low-dose niacin on dyslipidemia and serum phosphorus in patients with chronic kidney disease

BACKGROUND: Niacin supplementation improves dyslipidemia and lowers serum phosphorus levels in patients with chronic kidney disease (CKD). We evaluated whether low-dose niacin supplementation can improve dyslipidemia, lower serum phosphorus levels, and be administered with a low frequency of adverse effects in patients with CKD. METHODS: We retrospectively analyzed the clinical records of patients with CKD who had taken niacin from January 2009 to June 2011. We excluded patients with CKD stage 1 and 5. We then enrolled 31 patients with CKD who had taken niacin at a fixed dose of 500mg/day for 6 months. We also randomly selected 30 patients with CKD who had been taking statin for 9 months as a control group. RESULTS: Among the 34 patients with CKD who were prescribed niacin, five (14%) complained of adverse effects, and three (8%) discontinued niacin. The proportion of patients in the niacin group who had been taking a statin or omega-3 fatty acids was 67.7% and 48.8%, respectively. In the niacin group, high-density lipoprotein cholesterol level was significantly increased and triglyceride level was significantly decreased at 12 and 24 weeks compared with baseline levels (P < 0.05). In the niacin group, phosphorous level (P < 0.05) was significantly decreased, and glomerular filtration rate (GFR) was significantly increased (P < 0.05) at 24 weeks compared with baseline values. CONCLUSION: Low-dose niacin had a low frequency of adverse effects and also improved dyslipidemia, lowered serum phosphorus level, and increased GFR in patients with CKD. Further studies are needed to evaluate the long-term effects of low-dose niacin for renal progression of CKD.

Function of the Cold Receptor (TRPM8) Associated with Voiding Dysfunction in Bladder Outlet Obstruction in Rats / 대한배뇨장애요실금학회지

PURPOSE: Bladder outlet obstruction (BOO) causes storage and voiding dysfunction in the lower urinary tract. We investigated the expression of transient receptor potential cation channel subfamily M member 8 (TRPM8) to evaluate the relationship between TRPM8 expression and overactive bladder (OAB) in a rat model of BOO. METHODS: Fifty female Sprague-Dawley rats were divided into 4 groups; normal (n=10), normal-menthol (n=10), BOO (n=15), BOO-menthol (n=15). After 3 weeks, cystometry was performed by infusing physiological saline and menthol (3 mM) into the bladder at a slow infusion rate. The histological changes and expression of TRPM8 in the bladder were investigated by Masson's trichrome staining, immunofluorescence and reverse transcription-polymerase chain reaction. RESULTS: Cystometry showed that the intercontraction interval (ICI; 428.2+/-23.4 vs. 880.4+/-51.2, P<0.001), micturition pressure (MP; 25.7+/-1.01 vs. 71.80+/-3.01, P<0.001), and threshold pressure (2.9+/-0.25 vs. 9.2+/-1.58, P<0.01) were significantly increased in BOO rats. The bladder wall was significantly dilated compared with the control. Detrusor muscle hypertrophy and a thick mucosa layer were observed in BOO bladder. After menthol treatment, ICIs were decreased and MPs were increased in the menthol treatment groups. TRPM8-positive cells and mRNA were predominantly increased in the bladder and dorsal root ganglia of all groups compared with the normal group. CONCLUSIONS: Increased bladder wall thickness and proportion of collagen probably affect voiding dysfunction. Furthermore, an increase of TRPM8 expression in BOO may induce entry of Ca2+ from the extracellular space or stores. The increase of Ca2+ probably causes contraction of smooth muscle in BOO. However, OAB symptoms were not observed after menthol treatment although the expression of TRPM8 was abundant in the bladder epithelium after menthol treatment. Although OAB in BOO models may be caused by complex pathways, regulation of TRPM8 presents possibilities for OAB treatment.

Adult Onset Still's Disease Developed in a Patient with Membranous Nephropathy Treated with Immunosuppressive Agent / 대한신장학회지

Adult onset Still's disease (AOSD) is a rare systemic inflammatory disease characterized by high spiking fever, leukocytosis, high serum ferritin, salmon-colored rash, arthritis, lymphadenopathy, and hepatosplenomegaly. The etiology of AOSD is obscure. AOSD is diagnosed after exclusion of infection, malignancy and other connective tissue diseases. A 53-year-old female patient with membranous nephropathy was admitted with high fever and leukocytosis. She was taking immunosuppressive agents with low dose steroid and cyclosporine to control of proteinuria caused by membranous nephropathy. She was initially treated with antibiotics, antiviral agent and antifungal agent to control of hidden infection. High spiking fever was sustained for 2 weeks and controlled after hydrocortisone treatment. AOSD was diagnosed according to the criteria of Yamaguchi. It should be considered that AOSD is a cause of high fever in patients treated with immunosuppressive agents.