Comparison of non-contrast abbreviated MRI and ultrasound as surveillance modalities for HCC.

BACKGROUND & AIMS: Ultrasound (US) is recommended for HCC surveillance in high-risk patients but has limited performance in detecting early-stage HCC. We aimed to compare the diagnostic performance of biannual US and annual non-contrast abbreviated magnetic resonance imaging (NC-AMRI) as HCC surveillance modalities in high-risk patients. METHODS: This prospective, multicenter cohort study enrolled participants with an estimated annual risk of HCC greater than 5% between October 2015 and April 2017. Participants underwent six rounds of HCC surveillance at 6-month intervals, with both US and NC-AMRI at rounds 1, 3, and 5, and only US at rounds 2, 4, and 6. The sensitivity, diagnostic yield (DY), and false referral rate (FRR) for HCC detection by US and NC-AMRI were compared. RESULTS: In total, 208 participants underwent 980 US and 516 NC-AMRI examinations during 30 months of follow-up. Among them, 34 HCCs were diagnosed in 31 participants, with 20 (64.5%) classified as very early-stage and 11 (35.5%) as early-stage HCC. The sensitivity of annual NC-AMRI (71.0%, 22/31) was marginally higher than that of biannual US (45.2%, 14/31; p = 0.077). NC-AMRI showed a significantly higher DY than US (4.26% vs. 1.43%, p <0.001), with a similar FRR (2.91% vs. 3.06%, p = 0.885). A simulation of alternating US and NC-AMRI at 6-month intervals yielded a sensitivity of 83.9% (26/31), significantly exceeding that of biannual US (p = 0.006). CONCLUSIONS: Annual NC-AMRI showed a marginally higher sensitivity than biannual US for HCC detection in high-risk patients. The DY of annual NC-AMRI was significantly higher than that of biannual US, without increasing the FRR. Thus, alternating US and NC-AMRI at 6-month intervals could be an optimal surveillance strategy for high-risk patients. IMPACT AND IMPLICATIONS: Current guidelines permit the use of magnetic resonance imaging (MRI) as a surveillance tool for hepatocellular carcinoma in patients in whom ultrasonography (US) is inadequate. However, the specific indications, imaging sequences, and intervals for MRI surveillance remain unclear. In our study, we found that annual non-contrast abbreviated MRI exhibited marginally higher sensitivity and significantly better diagnostic yield than biannual US in patients at high risk of hepatocellular carcinoma. Alternating US and non-contrast abbreviated MRI at 6-month intervals led to significantly improved sensitivity compared to biannual US, making it a potentially optimal surveillance strategy for high-risk patients. GOV IDENTIFIER: NCT02551250.

Preoperative assessment of microvascular invasion risk using gadoxetate-enhanced MRI for predicting outcomes after liver transplantation for single hepatocellular carcinoma within the Milan criteria.

OBJECTIVE: To compare therapeutic outcomes after liver transplantation (LT) between hepatocellular carcinomas (HCC) with low and high risk for microvascular invasion (MVI) within the Milan criteria evaluated preoperatively. METHODS: Eighty patients with a single HCC who underwent LT as the initial therapy between 2008 and 2017 were included from two tertiary referral medical centers in a HBV-predominant population. A preoperative MVI-risk model was used to identify low- and high-risk patients. Recurrence-free survival (RFS) after LT between the two risk groups was compared using Kaplan-Meier curves with the log-rank test. Prognostic factors for RFS were identified using a multivariable Cox hazard regression analysis. RESULTS: Eighty patients were included (mean age, 51.8 years +/- 7.5 [standard deviation], 65 men). Patients were divided into low-risk (n = 64) and high-risk (n = 16) groups for MVI. The RFS rates after LT were significantly lower in the MVI high-risk group compared to the low-risk group at 1 year (75.0% [95% CI: 56.5-99.5%] vs. 96.9% [92.7-100%], p = 0.048), 3 years (62.5% [42.8-91.4%] vs. 95.3% [90.3-100%], p = 0.008), and 5 years (62.5% [42.8-91.4%] vs. and 95.3% [90.3-100%], p = 0.008). In addition, multivariable analysis showed that MVI high risk was the only significant factor for poor RFS (p = 0.016). CONCLUSION: HCC patients with a high risk of MVI showed significantly lower RFS after LT than those without. This model could aid in selecting optimal candidates in addition to the Milan criteria when considering upfront LT for patients with HCC if alternative treatment options are available. CLINICAL RELEVANCE STATEMENT: High risk for microvascular invasion (MVI) in hepatocellular carcinoma patients lowered recurrence-free survival after liver transplantation, despite meeting the Milan criteria. Identifying MVI risk could aid candidate selection for upfront liver transplantation, particularly if alternative treatments are available. KEY POINTS: • A predictive model-derived microvascular invasion (MVI) high- and low-risk groups had a significant difference in the incidence of MVI on pathology. • Recurrence-free survival after liver transplantation (LT) for single hepatocellular carcinoma (HCC) within the Milan criteria was significantly different between the MVI high- and low-risk groups. • The peak incidence of tumor recurrence was 20 months after liver transplantation, probably indicating that HCC with high risk for MVI had a high risk of early (≤ 2 years) tumor recurrence.

LI-RADS category is associated with treatment outcomes of small single HCC: surgical resection vs. radiofrequency ablation.

OBJECTIVES: To assess whether the Liver Imaging Reporting and Data System (LI-RADS) category is associated with the treatment outcomes of small single hepatocellular carcinoma (HCC) after surgical resection (SR) and radiofrequency ablation (RFA). METHODS: This retrospective study included 357 patients who underwent SR (n = 209) or RFA (n = 148) for a single HCC of ≤ 3 cm between 2014 and 2016. LI-RADS categories were assigned. Overall survival (OS), recurrence-free survival (RFS), and local tumor progression (LTP) rates after treatment were compared according to the LI-RADS category (LR-4/5 vs. LR-M) before and after propensity score matching (PSM). Prognostic factors for treatment outcomes were assessed. RESULTS: In total, 357 patients (mean age, 59 years; men, 272) with 357 HCCs (294 LR-4/5 and 63 LR-M) were included. After PSM (n = 78 in each treatment group), there were 10 and 11 LR-M HCCs in the SR and RFA group, respectively. There were no significant differences in OS or RFS. However, SR provided a lower 5-year LTP rate than RFA (1.4% vs. 14.9%, p = 0.001). SR provided a lower 5-year LTP rate than RFA for LR-M HCCs (0% vs. 34.4%, p = 0.062) and LR-4/5 HCCs (1.5% vs. 12.0%, p = 0.008). The LI-RADS category was the sole risk factor associated with poor OS (hazard ratio [HR] 3.79, p = 0.004), RFS (HR 2.12; p = 0.001), and LTP (HR 2.89; p = 0.032). CONCLUSION: LI-RADS classification is associated with the treatment outcome of HCC, supporting favorable outcomes of SR over RFA for LTP, especially for HCCs categorized as LR-M. CLINICAL RELEVANCE STATEMENT: Liver Imaging Reporting and Data System category has a potential prognostic role, supporting favorable outcomes of surgical resection over radiofrequency ablation for local tumor progression, especially for hepatocellular carcinoma categorized as LR-M. KEY POINTS: • SR provided a lower 5-year LTP rate than RFA for HCCs categorized as LR-M (0% vs. 34.4%, p = 0.062) and HCCs categorized as LR-4/5 (1.5% vs. 12.0%, p = 0.008). • There is a steeply increased risk of LTP within 1 year after RFA for LR-M HCCs, compared to SR. • The LI-RADS category was the sole risk factor associated with poor OS (HR 3.79, p = 0.004), RFS (HR 2.12; p = 0.001), and LTP (HR 2.89; p = 0.032) in patients with HCC of ≤ 3 cm treated with SR or RFA.

Consensus report from the 10th global forum for liver magnetic resonance imaging: multidisciplinary team discussion.

The 10th Global Forum for Liver Magnetic Resonance Imaging was held in October 2021. The themes of the presentations and discussions at this Forum are described in detail in the review by Taouli et al (2023). The focus of this second manuscript developed from the Forum is on multidisciplinary tumor board perspectives in hepatocellular carcinoma (HCC) management: how to approach early-, mid-, and late-stage management from the perspectives of a liver surgeon, an interventional radiologist, and an oncologist. The manuscript also includes a panel discussion by multidisciplinary experts on three selected cases that explore challenging aspects of HCC management. CLINICAL RELEVANCE STATEMENT: This review highlights the importance of a multidisciplinary team approach in liver cancer patients and includes the perspectives of a liver surgeon, an interventional radiologist, and an oncologist, including illustrative case studies. KEY POINTS: • A liver surgeon, interventional radiologist, and oncologist presented their perspectives on the treatment of early-, mid-, and late-stage HCC. • Different perspectives on HCC management between specialties emphasize the importance of multidisciplinary tumor boards. • A multidisciplinary faculty discussed challenging aspects of HCC management, as highlighted by three case studies.

Consensus report from the 10th Global Forum for Liver Magnetic Resonance Imaging: developments in HCC management.

The 10th Global Forum for Liver Magnetic Resonance Imaging (MRI) was held as a virtual 2-day meeting in October 2021, attended by delegates from North and South America, Asia, Australia, and Europe. Most delegates were radiologists with experience in liver MRI, with representation also from specialists in liver surgery, oncology, and hepatology. Presentations, discussions, and working groups at the Forum focused on the following themes: • Gadoxetic acid in clinical practice: Eastern and Western perspectives on current uses and challenges in hepatocellular carcinoma (HCC) screening/surveillance, diagnosis, and management • Economics and outcomes of HCC imaging • Radiomics, artificial intelligence (AI) and deep learning (DL) applications of MRI in HCC. These themes are the subject of the current manuscript. A second manuscript discusses multidisciplinary tumor board perspectives: how to approach early-, mid-, and late-stage HCC management from the perspectives of a liver surgeon, interventional radiologist, and oncologist (Taouli et al, 2023). Delegates voted on consensus statements that were developed by working groups on these meeting themes. A consensus was considered to be reached if at least 80% of the voting delegates agreed on the statements. CLINICAL RELEVANCE STATEMENT: This review highlights the clinical applications of gadoxetic acid-enhanced MRI for liver cancer screening and diagnosis, as well as its cost-effectiveness and the applications of radiomics and AI in patients with liver cancer. KEY POINTS: • Interpretation of gadoxetic acid-enhanced MRI differs slightly between Eastern and Western guidelines, reflecting different regional requirements for sensitivity vs specificity. • Emerging data are encouraging for the cost-effectiveness of gadoxetic acid-enhanced MRI in HCC screening and diagnosis, but more studies are required. • Radiomics and artificial intelligence are likely, in the future, to contribute to the detection, staging, assessment of treatment response and prediction of prognosis of HCC-reducing the burden on radiologists and other specialists and supporting timely and targeted treatment for patients.

Dose-escalated radiotherapy for clinically localized and locally advanced prostate cancer.

BACKGROUND: Treatments for clinically localized prostate cancer include radical prostatectomy, external beam radiation therapy, brachytherapy, active surveillance, hormonal therapy, and watchful waiting. For external beam radiation therapy, oncological outcomes may be expected to improve as the dose of radiotherapy (RT) increases. However, radiation-mediated side effects on surrounding critical organs may also increase. OBJECTIVES: To assess the effects of dose-escalated RT in comparison with conventional dose RT for curative treatment of clinically localized and locally advanced prostate cancer. SEARCH METHODS: We performed a comprehensive search using multiple databases including trial registries and other sources of grey literature, up until 20 July 2022. We applied no restrictions on publication language or status. SELECTION CRITERIA: We included parallel-arm randomized controlled trials (RCTs) of definitive RT in men with clinically localized and locally advanced prostate adenocarcinoma. RT was dose-escalated RT (equivalent dose in 2 Gy [EQD2] ≥ 74 Gy, lesser than 2.5 Gy per fraction) versus conventional RT (EQD2 < 74 Gy, 1.8 Gy or 2.0 Gy per fraction). Two review authors independently classified studies for inclusion or exclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data from the included studies. We performed statistical analyses by using a random-effects model and interpreted them according to the Cochrane Handbook for Systematic Reviews of Interventions. We used GRADE guidance to rate the certainty of the evidence of RCTs. MAIN RESULTS: We included nine studies with 5437 men in an analysis comparing dose-escalated RT versus conventional dose RT for the treatment of prostate cancer. The mean participant age ranged from 67 to 71 years. Almost all men had localized prostate cancer (cT1-3N0M0). Primary outcomes Dose-escalated RT probably results in little to no difference in time to death from prostate cancer (hazard ratio [HR] 0.83, 95% CI 0.66 to 1.04; I2 = 0%; 8 studies; 5231 participants; moderate-certainty evidence). Assuming a risk of death from prostate cancer of 4 per 1000 at 10 years in the conventional dose RT group, this corresponds to 1 fewer men per 1000 (1 fewer to 0 more) dying of prostate cancer in the dose-escalated RT group. Dose-escalated RT probably results in little to no difference in severe RT toxicity of grade 3 or higher late gastrointestinal (GI) toxicity (RR 1.72, 95% CI 1.32 to 2.25; I2 = 0%; 8 studies; 4992 participants; moderate-certainty evidence); 23 more men per 1000 (10 more to 40 more) in the dose-escalated RT group assuming severe late GI toxicity as 32 per 1000 in the conventional dose RT group. Dose-escalated RT probably results in little to no difference in severe late genitourinary (GU) toxicity (RR 1.25, 95% CI 0.95 to 1.63; I2 = 0%; 8 studies; 4962 participants; moderate-certainty evidence); 9 more men per 1000 (2 fewer to 23 more) in the dose-escalated RT group assuming severe late GU toxicity as 37 per 1000 in the conventional dose RT group. Secondary outcomes Dose-escalated RT probably results in little to no difference in time to death from any cause (HR 0.98, 95% CI 0.89 to 1.09; I2 = 0%; 9 studies; 5437 participants; moderate-certainty evidence). Assuming a risk of death from any cause of 101 per 1000 at 10 years in the conventional dose RT group, this corresponds to 2 fewer men per 1000 (11 fewer to 9 more) in the dose-escalated RT group dying of any cause. Dose-escalated RT probably results in little to no difference in time to distant metastasis (HR 0.83, 95% CI 0.57 to 1.22; I2 = 45%; 7 studies; 3499 participants; moderate-certainty evidence). Assuming a risk of distant metastasis of 29 per 1000 in the conventional dose RT group at 10 years, this corresponds to 5 fewer men per 1000 (12 fewer to 6 more) in the dose-escalated RT group developing distant metastases. Dose-escalated RT may increase overall late GI toxicity (RR 1.27, 95% CI 1.04 to 1.55; I2 = 85%; 7 studies; 4328 participants; low-certainty evidence); 92 more men per 1000 (14 more to 188 more) in the dose-escalated RT group assuming overall late GI toxicity as 342 per 1000 in the conventional dose RT group. However, dose-escalated RT may result in little to no difference in overall late GU toxicity (RR 1.12, 95% CI 0.97 to 1.29; I2 = 51%; 7 studies; 4298 participants; low-certainty evidence); 34 more men per 1000 (9 fewer to 82 more) in the dose-escalated RT group assuming overall late GU toxicity as 283 per 1000 in the conventional dose RT group. Based on long-term follow-up (up to 36 months), dose-escalated RT may result or probably results in little to no difference in the quality of life using 36-Item Short Form Survey; physical health (MD -3.9, 95% CI -12.78 to 4.98; 1 study; 300 participants; moderate-certainty evidence) and mental health (MD -3.6, 95% CI -83.85 to 76.65; 1 study; 300 participants; low-certainty evidence), respectively. AUTHORS' CONCLUSIONS: Compared to conventional dose RT, dose-escalated RT probably results in little to no difference in time to death from prostate cancer, time to death from any cause, time to distant metastasis, and RT toxicities (except overall late GI toxicity). While dose-escalated RT may increase overall late GI toxicity, it may result, or probably results, in little to no difference in physical and mental quality of life, respectively.

Phase-selective synthesis of lead-free CsMnBr3 and Cs3MnBr5 nanocrystals dependent on solvent concentration.

We demonstrate the crystal phase-selective synthesis for lead-free cesium manganese bromine perovskite nanocrystals synthesized by the modified hot-injection method due to changing the concentration of solvent (trioctylphosphine; TOP). The compositions synthesized were determined by the amount of TOP solvent, and the structure phase of the nanocrystals was selected from hexagonal CsMnBr3 to tetragonal Cs3MnBr5 as the amount of TOP solvent increased. The emission peaks of CsMnBr3 and Cs3MnBr5 nanocrystals were observed at 650 nm (red) and 520 nm (green), respectively. After a durability test at 85°C and 85% humidity for 24 h, the lead-free perovskite CsMnBr3 nanocrystal powder maintained its initial emission intensity, and the metal halide Cs3MnBr5 nanocrystal powder exhibited an increase in red emission due to the post-synthesis of CsMnBr3 nanocrystals.

A modified LI-RADS: targetoid tumors with enhancing capsule can be diagnosed as HCC instead of LR-M lesions.

OBJECTIVE: To elucidate whether the presence of enhancing capsule can be applied to establish a modified Liver Imaging Reporting and Data System (LI-RADS) to differentiate hepatocellular carcinoma (HCC) from non-HCC malignancies in extracellular contrast agent (ECA)-enhanced and hepatobiliary agent (HBA)-enhanced MRI. METHODS: We enrolled 198 participants (161 men; mean age, 56.3 years) with chronic liver disease who underwent ECA-MRI and HBA-MRI before surgery for de novo hepatic nodule(s). Two reviewers assigned LI-RADS categories (v2018). We defined a "modified LR-5 category, which emphasizes enhancing capsule (mLR-5C)" over targetoid features and classifies tumors with both targetoid appearance and enhancing capsule as HCC instead of LR-M. We compared the diagnostic performance of conventional LI-RADS and modified LI-RADS criteria for both MRIs. RESULTS: A total of 258 hepatic nodules (194 HCCs, 43 benign lesions, and 21 non-HCC malignancies; median size, 19 mm) were analyzed. By conventional LI-RADS, 47 (18.2%) nodules (31 HCCs and 16 non-HCC malignancies) were categorized as LR-M. The mLR-5C criterion showed superior sensitivity (ECA-MRI, 76.6% vs. 67.0%; HBA-MRI, 60.4% vs. 56.3%; both p < 0.05) while maintaining high specificity (ECA-MRI, 93.8% vs. 98.4%; HBA-MRI, 95.3% vs. 98.4%; both p > 0.05) compared with the LR-5 criterion. Using the mLR-5C criterion, ECA-MRI exhibited higher sensitivity than HBA-MRI (76.6% vs. 60.4%, p < 0.001) and similar specificity (93.8% vs. 95.3%, p > 0.99). CONCLUSION: Our modified LI-RADS achieved superior sensitivity for diagnosing HCC, without compromising specificity compared with LR-5. ECA-MRI showed higher sensitivity in diagnosing HCC than HBA-MRI by applying the mLR-5C for LR-M lesions. KEY POINTS: • By conventional LI-RADS, 31 (16.0%) of 194 HCCs were categorized as LR-M. • Among 31 HCCs categorized as LR-M, 19 HCCs or 8 HCCs were recategorized as HCC on ECA-MRI or HBA-MRI, respectively, after applying the modified LR-5 category, which allocates targetoid lesions with enhancing capsule as mLR-5C instead of LR-M. • The mLR-5C showed superior sensitivity compared with the LR-5 in both MRIs (ECA-MRI, 76.6% vs. 67.0%; HBA-MRI, 60.4% vs. 56.3%, both p < 0.05), while maintaining high specificity (ECA-MRI, 93.8% vs. 98.4%; HBA-MRI, 95.3% vs. 98.4%; both p > 0.05).

Utility of Diffusion-Weighted MRI for Detection of Locally Recurrent Pancreatic Cancer After Surgical Resection.

BACKGROUND. Overlapping imaging findings between local tumor recurrence and postsurgical fibrosis represent a major clinical challenge after pancreatic ductal adeno-carcinoma (PDAC) resection. OBJECTIVE. The purpose of this study was to compare the diagnostic performance of MRI with and without DWI for differentiating locally recurrent tumor and postsurgical fibrosis after PDAC resection. METHODS. This retrospective study included 66 patients (35 men, 31 women; mean age, 60.5 years) who underwent PDAC resection between January 2009 and March 2016, postoperative surveillance CT showing a soft-tissue lesion at the operative site or at the site of peripancreatic vessels, and subsequent MRI with DWI for further evaluation. CT at least 6 months after MRI served as the reference standard, with increase in size of the soft tissue by 5 mm or more differentiating locally recurrent tumor (n = 26) and postsurgical fibrosis (n = 40). Two observers in consensus evaluated MRI characteristics of the soft-tissue lesions. Two additional observers independently reviewed MRI examinations in two separate sessions (conventional MRI alone vs MRI with DWI), recording likelihood of recurrent tumor using a 1-5 scale. ROC analysis was performed, considering scores of 4 or 5 as positive. RESULTS. Subjective diffusion restriction was more common in locally recurrent tumor than postsurgical fibrosis (88.5% vs 25.0%, p = .01). Median ADC was lower for locally recurrent tumor than postsurgical fibrosis (1.3 vs 1.7 × 10-3 mm2/s, p < .001). For both observers, MRI with DWI in comparison with conventional MRI alone showed higher AUC for diagnosis of locally recurrent tumor (observer 1: 0.805 vs 0.707, p = .048; observer 2: 0.898 vs 0.637, p < .001) and higher sensitivity (observer 1: 88.5% vs 61.5%, p = .008; observer 2: 84.6% vs 42.3%, p = .001) but no difference in specificity (observer 1: 72.5% vs 80.0%, p = .08; observer 2, 95.0% vs 85.0%, p = .10). Interobserver agreement was moderate for conventional MRI (κ = 0.41) and good for conventional MRI with DWI (κ = 0.62). CONCLUSION. The addition of DWI to conventional MRI improves the differentiation of locally recurrent tumor and postsurgical fibrosis after PDAC resection, primarily because of improved sensitivity for recurrence. CLINICAL IMPACT. The findings indicate a potential role for MRI with DWI in surveillance protocols after PDAC resection.

Laparoscopic radiofrequency ablation of subcapsular hepatocellular carcinomas: risk factors related to a technical failure.

BACKGROUND: This study aimed to evaluate the risk factors related to a technical failure after laparoscopic radiofrequency ablation (RFA) for subcapsular hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: A total of 110 patients with 114 HCCs who underwent laparoscopic RFA for HCCs (new HCC [n = 85] and local tumor progression [LTP] [n = 29]) between January 2013 and December 2018 were included. We evaluated the incidence of technical failure on immediate post-RFA CT images. Risk factors for a technical failure after laparoscopic RFA were assessed using univariable logistic regression analyses. The cumulative LTP rate was estimated using the Kaplan-Meier method. RESULTS: Technical failure was noted in 3.5% (4/114) of the tumors. All four tumors that showed a technical failure were cases of LTP from previous treatment and were invisible on laparoscopy. On univariate analysis, LTP lesion, invisibility of the index tumor on laparoscopy, and peri-hepatic vein location of the tumor were identified as risk factors for a technical failure. The cumulative LTP rates at 1, 3, and 5 years were estimated to be 2.8%, 4.8%, and 4.8%, respectively. CONCLUSIONS: LTP lesion, invisibility of the index tumor on laparoscopy, and peri-hepatic vein location of the tumor were identified as the risk factors for a technical failure after laparoscopic RFA.

Urine-Derived Stem Cell-Secreted Klotho Plays a Crucial Role in the HK-2 Fibrosis Model by Inhibiting the TGF-ß Signaling Pathway.

Renal fibrosis is an irreversible and progressive process that causes severe dysfunction in chronic kidney disease (CKD). The progression of CKD stages is highly associated with a gradual reduction in serum Klotho levels. We focused on Klotho protein as a key therapeutic factor against CKD. Urine-derived stem cells (UDSCs) have been identified as a novel stem cell source for kidney regeneration and CKD treatment because of their kidney tissue-specific origin. However, the relationship between UDSCs and Klotho in the kidneys is not yet known. In this study, we discovered that UDSCs were stem cells that expressed Klotho protein more strongly than other mesenchymal stem cells (MSCs). UDSCs also suppressed fibrosis by inhibiting transforming growth factor (TGF)-ß in HK-2 human renal proximal tubule cells in an in vitro model. Klotho siRNA silencing reduced the TGF-inhibiting ability of UDSCs. Here, we suggest an alternative cell source that can overcome the limitations of MSCs through the synergetic effect of the origin specificity of UDSCs and the anti-fibrotic effect of Klotho.

Effect of Microvascular Invasion Risk on Early Recurrence of Hepatocellular Carcinoma After Surgery and Radiofrequency Ablation.

OBJECTIVE: We compared surgical resection (SR) and radiofrequency ablation (RFA) as first-line treatment in patients with hepatocellular carcinoma (HCC) based on the risk of microvascular invasion (MVI). BACKGROUND: The best curative treatment modality between SR and RFA in patients with HCC with MVI remains unclear. METHODS: Data from 2 academic cancer center-based cohorts of patients with a single, small (≤3 cm) HCC who underwent SR were used to derive (n = 276) and validate (n = 101) prediction models for MVI using clinical and imaging variables. The MVI prediction model was developed using multivariable logistic regression analysis and externally validated. Early recurrence (<2 years) based on risk stratification between SR (n = 276) and RFA (n = 240) was evaluated via propensity score matching. RESULTS: In the multivariable analysis, alpha-fetoprotein (≥15 ng/mL), protein induced by vitamin K absence-II (≥48 mAU/mL), arterial peritumoral enhancement, and hepatobiliary peritumoral hypointensity on magnetic resonance imaging were associated with MVI. Incorporating these factors, the area under the receiver operating characteristic curve of the predictive model was 0.87 (95% confidence interval: 0.82-0.92) and 0.82 (95% confidence interval: 0.74-0.90) in the derivation and validation cohorts, respectively. SR was associated with a lower rate of early recurrence than RFA based on the risk of MVI after propensity score matching (P < 0.05). CONCLUSIONS: Our model predicted the risk of MVI in patients with a small (≤ 3 cm) HCC with high accuracy. Patients with MVI who had undergone RFA were more vulnerable to recurrence than those who had undergone SR.

Comparison of Super-Resolution US and Contrast Material-enhanced US in Detection of the Spoke Wheel Sign in Patients with Focal Nodular Hyperplasia.

Background Diagnosis of focal nodular hyperplasia (FNH) with US generally requires the use of contrast material. The effect of the super-resolution US technique on the diagnosis of FNH is unknown. Purpose To investigate the equivalence between super-resolution US and contrast material-enhanced US in the detection of spoke wheel sign in patients with FNH by comparing patterns of tumor vascularity. Materials and Methods This is a secondary analysis of a prospective trial (NCT02737865) that enrolled participants diagnosed with FNH between May 2016 and March 2019. These patients underwent super-resolution US and subsequent contrast-enhanced US with perfluorobutane microbubbles on the same day. The primary outcome was the confidence score of detecting spoke wheel sign in patients with FNH at US. Two radiologists used a four-point scale to score their confidence in the presence of the spoke wheel sign based on super-resolution US and contrast-enhanced US findings. Two one-sided tests were used to test the equivalence between super-resolution US and contrast-enhanced US in terms of the score for the confidence level of the spoke wheel sign. Interobserver agreement for both techniques between the two radiologists, using the recorded images, was analyzed by using an intraclass correlation coefficient. Results In 62 patients (mean age, 37 years; range, 20-69 years; 41 women) with FNH, the majority of patients showed a spoke wheel sign at super-resolution US and contrast-enhanced US (63% [39 of 62] and 71% [44 of 62], respectively; P = .36). There was no significant difference between the super-resolution US and contrast-enhanced US techniques regarding the confidence score for the spoke wheel sign (mean score, 1.8 vs 2.0; P = .03 for equivalence test). The intraclass correlation coefficients of super-resolution US and contrast-enhanced US regarding the presence of the spoke wheel sign were 0.82 (95% confidence interval: 0.73, 0.96) and 0.58 (95% confidence interval: 0.41, 0.73), respectively. Conclusion In comparison with contrast-enhanced US, super-resolution US provided a reliable rate of detection of the spoke wheel sign in patients with focal nodular hyperplasia. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Fetzer in this issue.

Consensus Guidelines for the Definition of Time-to-Event End Points in Image-guided Tumor Ablation: Results of the SIO and DATECAN Initiative.

There is currently no consensus regarding preferred clinical outcome measures following image-guided tumor ablation or clear definitions of oncologic end points. This consensus document proposes standardized definitions for a broad range of oncologic outcome measures with recommendations on how to uniformly document, analyze, and report outcomes. The initiative was coordinated by the Society of Interventional Oncology in collaboration with the Definition for the Assessment of Time-to-Event End Points in Cancer Trials, or DATECAN, group. According to predefined criteria, based on experience with clinical trials, an international panel of 62 experts convened. Recommendations were developed using the validated three-step modified Delphi consensus method. Consensus was reached on when to assess outcomes per patient, per session, or per tumor; on starting and ending time and survival time definitions; and on time-to-event end points. Although no consensus was reached on the preferred classification system to report complications, quality of life, and health economics issues, the panel did agree on using the most recent version of a validated patient-reported outcome questionnaire. This article provides a framework of key opinion leader recommendations with the intent to facilitate a clear interpretation of results and standardize worldwide communication. Widespread adoption will improve reproducibility, allow for accurate comparisons, and avoid misinterpretations in the field of interventional oncology research. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Liddell in this issue.

Eu3+-doped Bi2MoO6 phosphors for highly sensitive and visible H2S gas indicator material: optical and color properties, and gas sensing performance.

Bi2MoO6:Eu3+ phosphors were synthesized by a solid state reaction, and H2S gas sensing performance was investigated. The Bi2MoO6:Eu3+ phosphors showed an excellent red emission due to f-f transition of Eu3+. Owing to the exposure to H2S gas, the emission intensity of the phosphors dramatically decreased to 40% of the initial value. The body color of the phosphor changed from yellow-white to dark brown. The response of the Bi2MoO6:Eu3+ phosphors for H2S gas was started from 10 ppm, and the emission intensity exponentially decreased with increasing the concentration until 500 ppm.

EASL versus LI-RADS: Intra-individual comparison of MRI with extracellular contrast and gadoxetic acid for diagnosis of small HCC.

BACKGROUND & AIMS: Liver Imaging Reporting and Data System (LI-RADS) and European Association for the Study (EASL) criteria for hepatocellular carcinoma (HCC) diagnosis have been updated in 2018. We aimed to compare the HCC diagnostic performance of LI-RADS and EASL criteria with extracellular contrast agents-MRI (ECA-MRI) and hepatobiliary agents-MRI (HBA-MRI). METHODS: We prospectively evaluated 179 participants with cirrhosis (n = 105) or non-cirrhotic chronic hepatitis B (CHB) (n = 74) who underwent both ECA-MRI and HBA-MRI before surgery for de novo nodule(s) measuring 10-30 mm. We compared the HCC diagnostic performance of EASL and LR-5 in both MRIs. RESULTS: In an analysis of 215 observations (175 HCCs, 17 non-HCC malignancies and 23 benign lesions) identified from cirrhotic or non-cirrhotic CHB participants, LR-5 with ECA-MRI provided the highest sensitivity (80.7%), followed by EASL with ECA-MRI (76.2%), LR-5 with HBA-MRI (67.3%) and EASL with HBA-MRI (63.0%, all P < .05). The specificities were comparable (89.4%-91.5%). When the analysis is limited to participants with pathological cirrhosis (123 observations), the sensitivity of LR-5 with ECA-MRI was similar to that of EASL with ECA-MRI (82.7% vs 80.2%, P = .156), but higher than LR-5 with HBA-MRI (65.1%) or EASL with HBA-MRI (62.8%, both P < .001), with comparable specificities (87.5%-91.7%). CONCLUSIONS: The LR-5 with ECA-MRI yielded the highest sensitivity with a similar specificity for HCC diagnosis in cirrhosis and non-cirrhotic CHB participants, while the sensitivities of LR-5 and EASL with ECA-MRI are similar for cirrhosis participants. This indicates non-invasive diagnosis criteria can differ by contrast agents and presence of cirrhosis.

Assessment of factors affecting washout appearance of hepatocellular carcinoma on CT.

OBJECTIVES: To identify independent imaging and histopathologic factors that affect washout appearance of hepatocellular carcinoma (HCC) in CT images. METHODS: This retrospective study included 264 patients who had undergone surgical resection for treatment-naïve single HCC between January 2014 and December 2015 and had available preoperative multiphasic CT images. Two reviewers evaluated the CT imaging features of HCC using LI-RADS v2018. The "washout" was visually assessed in portal venous or equilibrium phases. Depending on the presence of washout appearance of HCC, all patients were divided into "washout" (n = 228) and "no washout" (n = 36) groups. Multivariable logistic regression analysis was used to identify factors associated with the absence of washout appearance of HCC. RESULTS: A total of 264 HCCs (median size, 2.6 cm) were analyzed. Histologically proven hepatic steatosis (macrovesicular steatosis ≥ 5%) (odds ratio [OR], 2.65; 95% confidence interval [CI], 1.05-6.74; p = 0.040), tumor capsule on histopathology (OR, 0.17; 95% CI, 0.06-0.50; p = 0.001), and mosaic appearance on CT image (OR, 0.34; 95% CI, 0.14-0.85; p = 0.021) were independent factors associated with the absence of washout appearance of HCC. In 189 patients with available unenhanced CT images, CT-diagnosed hepatic steatosis was also an independent factor for the absence of washout appearance of HCC (OR, 9.26; 95% CI, 3.06-28.02; p < 0.001). CONCLUSIONS: Washout appearance of HCC in CT images could be obscured in both histologically proven hepatic steatosis and CT-diagnosed hepatic steatosis, and could be enhanced with tumor capsule on histopathology and mosaic appearance on CT image. KEY POINTS: • Hepatic steatosis is an independent factor related to the absence of washout appearance of hepatocellular carcinoma in CT images, in both histologically proven hepatic steatosis and CT-diagnosed hepatic steatosis. • Both histologically proven hepatic steatosis and CT-diagnosed hepatic steatosis have higher odds of absence of washout appearance of hepatocellular carcinoma compared to non-steatotic liver. • Tumor capsule on histopathology and mosaic appearance on CT image are independent factors that enhance the probability that washout appearance of hepatocellular carcinoma is visible.

Rim-arterial enhancing primary hepatic tumors with other targetoid appearance show early recurrence after radiofrequency ablation.

OBJECTIVES: To evaluate early (≤ 2 years) local tumor progression (LTP), intrahepatic distant metastasis (IDR), and extrahepatic metastasis (EM) of primary hepatic malignant tumors with arterial rim enhancement (RE) after RFA in comparison with non-RE tumors. METHODS: Three hundred forty-nine patients who underwent RFA for primary hepatic malignant tumors between January 2009 and December 2016 were included. The patients' tumors were classified into non-RE, RE only (RO), and RE plus other targetoid appearances (REoT). Cumulative LTP, IDR, and EM rates at 1 and 2 years after RFA were calculated using the Kaplan-Meier method and compared using the log-rank test. Prognostic factors for the outcomes were assessed using a Cox proportional hazards model. RESULTS: There were 303 non-RE, 19 RO, and 27 REoT tumors. The REoT tumors had a significantly higher rate of IDR and EM than non-RE (p = 0.04 for IDR; and p < 0.01 for EM, respectively) at 1 year after RFA. At 2 years, LTP and EM rates were significantly higher for REoT than for non-RE (p = 0.001 for LTP; and p = 0.444 for EM, respectively). The RO tumors did not have different outcomes than non-RE at 1 and 2 years after RFA. Multivariable analysis verified that REoT was a significant factor for IDR (p = 0.04) and EM (p = 0.01) at 1 year and LTP (p = 0.02) at 2 years. CONCLUSIONS: Tumors with REoT had poor LTP, IDR, and EM within 2 years after RFA than non-RE tumors. However, tumors with RO showed similar results as non-RE tumors. KEY POINTS: • Tumors with Rim enhancement plus other targetoid appearances (REoT) had a significantly higher rate of recurrence than non-rim enhancing (RE) tumors at 1 and 2 years after RFA. • Tumors with rim enhancement only did not have different outcomes than non-RE at 1 and 2 years after RFA.

Vanishing washout of hepatocellular carcinoma according to the presence of hepatic steatosis: diagnostic performance of CT and MRI.

OBJECTIVES: To compare the presence of washout and the diagnostic performance of computed tomography (CT) and magnetic resonance imaging (MRI) for hepatocellular carcinoma (HCC) according to the presence of hepatic steatosis. METHODS: This retrospective study included 566 patients with chronic liver disease who had undergone hepatic resection for hepatic tumors (482 HCCs and 84 non-HCCs) between January 2016 and June 2018 and had available multiphasic CT and MR images. Patients were allocated in the fatty liver (n = 141) or non-fatty liver (n = 425) group according to the presence of hepatic steatosis, defined as lipid droplets in at least 5% of hepatocytes on pathological examination. The presence of HCC washout and the diagnostic performance of CT and MRI for HCC were compared between the groups. RESULTS: HCC washout was less frequently seen in the fatty liver group than in the non-fatty liver group on CT (61.5% vs. 88.9%, p < 0.001), whereas it was similarly present on MRI in both groups (77.0% vs. 74.4%, p = 0.565). For diagnosis of HCC, the sensitivity (53.3% vs. 80.0%, p < 0.001) and accuracy (53.9% vs. 80.9%, p < 0.001) of CT were lower in the fatty liver group than in the non-fatty liver group. However, for MRI, these values were not significantly different between the groups (p > 0.05). CONCLUSIONS: Hepatic steatosis significantly decreased the performance of CT for the diagnosis of HCC, whereas it did not significantly alter the performance of MRI. KEY POINTS: • Unlike MRI, there is vanishing HCC washout on CT caused by the background hepatic steatosis. • The diagnostic performance of CT for the diagnosis of HCC was significantly altered by hepatic steatosis. • The optimal cutoff HU value of the liver parenchyma for the vanishing washout of HCC was < 50 HU on unenhanced CT images.

Magnetic Resonance Imaging With Extracellular Contrast Detects Hepatocellular Carcinoma With Greater Accuracy Than With Gadoxetic Acid or Computed Tomography.

BACKGROUND & AIMS: Computed tomography (CT) and magnetic resonance imaging (MRI) are used to detect hepatocellular carcinoma (HCC). We performed a prospective study to compare the diagnostic performance of CT, MRI with extracellular contrast agents (ECA-MRI), and MRI with hepatobiliary agents (HBA-MRI) in the detection of HCC using the liver imaging reporting and data system (LI-RADS). METHODS: We studied 125 participants (102 men; mean age, 55.3 years) with chronic liver disease who underwent CT, ECA-MRI, or HBA-MRI (with gadoxetic acid) before surgery for a nodule initially detected by ultrasound at a tertiary center in Korea, from November 2016 through February 2019. We collected data on major features and assigned LI-RADS categories (v2018) from CT and MRI examinations. We then compared the diagnostic performance for LR-5 for each modality alone, and in combination. RESULTS: In total, 163 observations (124 HCCs, 13 non-HCC malignancies, and 26 benign lesions; mean size, 20.7 mm) were identified. ECA-MRI detected HCC with 83.1% sensitivity and 86.6% accuracy, compared to 64.4% sensitivity and 71.8% accuracy for CT (P < .001) and 71.2% sensitivity (P = .005) and 76.5% accuracy for HBA-MRI (P = .005); all technologies detected HCC with 97.4% specificity. Adding CT to either ECA-MRI (89.2% sensitivity, 91.4% accuracy; both P < .05) or HBA-MRI (82.8% sensitivity, 86.5% accuracy; both P < .05) significantly increased its diagnostic performance in detection of HCC compared with the MRI technologies alone. ECA-MRI identified arterial phase hyperenhancement in a significantly higher proportion of patients (97.6%) than CT (81.5%; P < .001) or HBA-MRI (89.5%; P = .002). ECA-MRI identified non-peripheral washout in 79.8% of patients, vs 74.2% of patients for CT and 73.4% of patients for HBA-MRI (differences not significant). ECA-MRI identified enhancing capsules in 85.5% of patients, vs 33.9% for CT (P < .001) and 41.4% for HBA-MRI (P < .001). CONCLUSION: In a prospective study of patients with chronic liver disease and a nodule detected by ultrasound, ECA-MRI detected HCC with higher levels of sensitivity and accuracy than CT or HBA-MRI, based on LI-RADS. Diagnostic performance was best when CT was used in combination with MRI compared with MRI alone.