Suboptimal performance of LI-RADS v2018 on gadoxetic acid-enhanced MRI for detecting hepatocellular carcinoma in liver transplant candidates.

OBJECTIVES: To evaluate the diagnostic performance for hepatocellular carcinoma (HCC) detection of the Liver Imaging Reporting and Data System (LI-RADS) version 2018 on gadoxetic acid-enhanced MRI, comparing liver transplant candidates (LT group) with patients who underwent surgical resection (SR group), and to determine significant clinical factors for diagnostic performance of LI-RADS v2018. METHODS: Patients who underwent gadoxetic acid-enhanced MRI and subsequent SR or LT for HCC were retrospectively included between January 2019 and December 2020. The sensitivity and specificity of LI-RADS LR-5 for HCC were compared between the two groups using generalized estimating equations. The accuracy of patient allocation according to the Milan criteria was calculated for the LT group. Univariable and multivariable logistic regression analyses were performed to determine significant clinical factors associated with the sensitivity of LI-RADS. RESULTS: Of the 281 patients, 237 were assigned to the SR group, and 44 were assigned to the LT group. The LT group showed significantly lower per-patient (48.5% vs. 79.6%, p < .001) and per-lesion sensitivity (31.0% vs. 75.9%, p < .001) than the SR group, whereas no significant difference in both per-patient (100.0% vs. 91.7%, p > .99) and per-lesion specificities (100.0% vs. 94.1%, p > .99). The accuracy of patient allocation was 50.0%. Sensitivity was significantly lower in patients with a smaller lesion size (p < .001), a larger lesion number (p = .002), and a higher Child-Pugh score (p = .009). CONCLUSION: LI-RADS v2018 on gadoxetic acid-enhanced MRI might be insufficient in liver transplant candidates and other diagnostic imaging tests should be considered in patients with these significant clinical factors. CLINICAL RELEVANCE STATEMENT: In liver transplant candidates with a smaller lesion size, a larger lesion number, and a higher Child-Pugh score, imaging tests other than gadoxetic acid-enhanced MRI may be clinically useful to determine the transplant eligibility. KEY POINTS: • The sensitivity of the Liver Imaging Reporting and Data System (LI-RADS) was lower in liver transplant candidates than in those who underwent surgical resection. • With the use of gadoxetic acid-enhanced MRI, the accuracy of patient allocation for liver transplantation on the basis of the Milan criteria was suboptimal. • The sensitivity of LI-RADS v2018 was significantly associated with lesion size, lesion number, and Child-Pugh classification.

LI-RADS threshold growth based on tumor growth rate can improve the diagnosis of hepatocellular carcinoma ≤ 3.0 cm.

OBJECTIVE: Despite the revision of threshold growth (TG) in the Liver Imaging Reporting and Data System (LI-RADS) version 2018, the appropriate time period between the two examinations for TG has not been determined. We compared the accuracy of LI-RADS with TG based on tumor growth rate for the diagnosis of hepatocellular carcinoma (HCC) with that of LI-RADS v2018 based on the original TG. METHODS: Patients who underwent preoperative MRI for focal solid lesions (≤ 3.0 cm) were retrospectively evaluated. Three readers measured the size of each lesion on prior CT/MRI and index MRI, with tumor growth rate defined as the percent change in lesion size per month. In addition to the original TG (≥ 50% size increase within ≤ 6 months), the modified TG based on tumor growth rates ≥ 10%/month (TG-10%), ≥ 20%/month (TG-20%), and ≥ 30%/month (TG-30%) were evaluated. The accuracies of these evaluation methods for LI-RADS category 5 HCC were compared using generalized estimation equations. RESULTS: A total of 508 lesions from 370 patients were evaluated. Compared with LI-RADS v2018 with the original TG, the accuracy of LI-RADS with TG-10% was significantly higher (85.0% vs. 80.7%, p < .001), whereas the accuracies of LI-RADS with TG-20% (81.3% vs. 80.7%, p = .404) and TG-30% (79.3% vs. 80.7%, p = .052) were not significant. The sensitivity of LI-RADS with TG-10% was higher than that of LI-RADS v2018 (79.0% vs. 72.5%, p < .001), whereas their specificities were not significantly different (96.6% vs. 96.6%, p > .999). CONCLUSION: TG-10% improved the sensitivity of LI-RADS by detecting additional hepatocellular carcinomas underestimated due to short-term follow-up. CLINICAL RELEVANCE STATEMENT: Threshold growth based on tumor growth rate can be clinically useful in the diagnosis of hepatocellular carcinoma, by improving the sensitivity of LI-RADS. KEY POINTS: • The diagnostic accuracy of Liver Imaging Reporting and Data System (LI-RADS) v2018 was not significantly affected by the time interval between prior and index assessments of threshold growth. • In the 334 hepatocellular carcinomas, the frequency of threshold growth was significantly higher using tumor growth rate ≥ 10%/month (TG-10%) than original threshold growth (53.3% vs. 18.0%, p < .001). • Compared with LI-RADS v2018 with the original threshold growth, LI-RADS with TG-10% had significantly higher accuracy (85.0% vs. 80.7%, p < .001) and sensitivity (79.0% vs. 72.5%, p < .001) but a similar specificity (96.6% vs. 96.6%, p > .999).

Radiofrequency ablation of subcapsular versus nonsubcapsular hepatocellular carcinomas ≤ 3 cm: analysis of long-term outcomes from two large-volume liver centers.

OBJECTIVES: To compare the safety and efficacy of RFA for single HCCs ≤ 3 cm in subcapsular versus nonsubcapsular locations using a propensity score matched analysis. MATERIALS AND METHODS: This retrospective study included patients with solitary HCCs ≤ 3 cm in size who underwent percutaneous RFA from 2005 to 2015 as initial treatment at two large-volume liver centers. Patients were divided into two groups, consisting of those with subcapsular and nonsubcapsular tumor locations. Complications, local tumor progression (LTP), and overall survival (OS) were compared in these two groups before and after propensity score matching (PSM). RESULTS: The study population consisted of 964 patients (712 men [74%]) of mean age 58.3 years. Of these 964 patients, 561 (58%) had nonsubcapsular and 403 (42%) had subcapsular HCCs. PSM generated 402 pairs of patients. Major complication rate was low, but significantly higher in the subcapscular group (p = 0.047). Rates of technical effectiveness in these two groups were 99% and 98%, respectively (p = 0.315). However, during follow-up, cumulative 1-, 3-, 5-, and 10-year LTP and OS rates did significantly differ in both entire and PSM cohorts, resulting in the latter 8%, 15%, 20%, and 26% in the nonsubcapsular group vs. 13%, 24%, 30%, and 31% in the subcapsular group (p = 0.015), and 99%, 91%, 80%, and 59% vs. 98%, 85%, 73%, and 50% in the two groups (p = 0.004), respectively. CONCLUSION: Rates of major complications, LTP, and OS differed significantly following first-line RFA treatment of single HCCs ≤ 3 cm in favor of the nonsubcapsular locations. CLINICAL RELEVANCE STATEMENT: This large-scale study provides evidence that radiofrequency ablation for small (≤ 3 cm) hepatocellular carcinomas is safer and more effective in nonsubcapsular location than in subcapsular location. KEY POINTS: • There exist conflicting outcomes on the effectiveness of RFA for early HCC depending on tumor location. • Rate of local tumor progression was significantly higher in the subcapsular hepatocellular carcinomas. • Overall survival rate was significantly poorer in the subcapsular hepatocellular carcinomas.

Chemoembolization versus radiofrequency ablation for single small (≤ 3 cm) hepatocellular carcinoma: a propensity score matching analysis.

OBJECTIVES: To compare the efficacy of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for patients with single small (≤ 3 cm) hepatocellular carcinoma (HCC) and preserved liver function (Child-Pugh class A). MATERIALS AND METHODS: The clinical features of treatment-naïve patients who underwent TACE and RFA as first-line treatment were balanced through propensity score matching (PSM). The primary endpoint was overall survival (OS), and the secondary endpoints were local tumor recurrence (LTR) and recurrence-free survival (RFS). RESULTS: The analysis included 440 patients who received TACE, and 430 patients who received RFA. After PSM adjustment (323 pairs), the 5- and 10-year OS rates were 81% and 61%, respectively, in patients who underwent RFA, and 77% and 51%, respectively, for patients who underwent TACE (p = 0.021). Subgroup analyses showed that OS, LTR, and RFS were homogeneously better in the RFA group. CONCLUSION: RFA was associated with better survival outcomes than TACE in patients with single small HCC and preserved liver function. CLINICAL RELEVANCE STATEMENT: This large-scale comparative study provides evidence that radiofrequency ablation has a better overall survival rate than chemoembolization for small (≤ 3 cm) hepatocellular carcinomas. KEY POINTS: • The relative effectiveness of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for early HCC is unclear. • Overall survival rate was significantly higher in the RFA group. • The effects of RFA on overall survival, local tumor recurrence, and recurrence-free survival were homogeneously better in all subgroups.

Value of threshold growth as a major diagnostic feature of hepatocellular carcinoma in LI-RADS.

BACKGROUND & AIMS: The Liver Reporting and Data System (LI-RADS) version 2018 simplified the definition of threshold growth to '≥50% size increase in a mass in ≤6 months'. However, the diagnostic value of threshold growth for hepatocellular carcinoma (HCC) remained unclear. We evaluated the value of threshold growth, as defined by LI-RADS v2018, in diagnosing HCCs. METHODS: Patients who underwent preoperative gadoxetate disodium-enhanced MRI because of the presence of LI-RADS category 2, 3, or 4 rather than category 5 on prior CT/MRI between January 2017 and December 2020 were retrospectively evaluated. Pathologic or clinical diagnoses were used as reference standards. Imaging features were evaluated by three readers according to LI-RADS v2018. The frequency and diagnostic odds ratio of threshold growth were calculated. The diagnostic performance of LI-RADS category 5 was separately evaluated when threshold growth was and was not considered a major feature, and results were compared using generalized estimation equations. Subgroups of patients who underwent CT/MRI during the previous 3-6 months were analyzed. RESULTS: Analysis of 340 observations in 243 patients found that the frequency of threshold growth was 18.8% and it gradually increased over time. Threshold growth was significantly associated with HCC (diagnostic odds ratio 5.2; 95% CI 2.1-12.7; p <0.001). Use of threshold growth as a major feature significantly increased sensitivity in both the overall (66.4% vs. 57.3%, p <0.001) and subgroup (73.4% vs. 58.2%, p <0.001) cohorts, but had no effect on specificity in either the overall (97.5% vs. 98.3%, p = 0.319) or subgroup (95.9% vs. 98.0%, p = 0.323) cohorts. CONCLUSION: The revised threshold growth of LI-RADS v2018 was significantly associated with HCC. Use of threshold growth as a major diagnostic feature of HCC can improve the sensitivity of LI-RADS v2018. IMPACT AND IMPLICATIONS: We found that the revised threshold growth in the Liver Imaging Reporting and Data System version 2018 (LI-RADS v2018) was a significant predictor of hepatocellular carcinoma (HCC). The use of threshold growth as a major imaging feature of HCC significantly increased the sensitivity of LI-RADS v2018, especially small HCCs (≤3.0 cm), compared with its non-use. Because these small HCCs are eligible for curative treatments, the additional detection of small HCCs is clinically meaningful.

Increased miR-200c levels disrupt palatal fusion by affecting apoptosis, cell proliferation, and cell migration.

The mammalian palate separates the oral and nasal cavities, facilitating proper feeding, respiration, and speech. Palatal shelves, composed of neural crest-derived mesenchyme and surrounding epithelium, are a pair of maxillary prominences contributing to this structure. Palatogenesis reaches completion upon the fusion of the midline epithelial seam (MES) following contact between medial edge epithelium (MEE) cells in the palatal shelves. This process entails numerous cellular and molecular occurrences, including apoptosis, cell proliferation, cell migration, and epithelial-mesenchymal transition (EMT). MicroRNAs (miRs) are small, endogenous, non-coding RNAs derived from double-stranded hairpin precursors that regulate gene expression by binding to target mRNA sequences. Although miR-200c is a positive regulator of E-cadherin, its role in palatogenesis remains unclear. This study aims to explore the role of miR-200c in palate development. Before contact with palatal shelves, mir-200c was expressed in the MEE along with E-cadherin. After palatal shelf contact, miR-200c was present in the palatal epithelial lining and epithelial islands surrounding the fusion region but absent in the mesenchyme. The function of miR-200c was investigated by utilizing a lentiviral vector to facilitate overexpression. Ectopic expression of miR-200c resulted in E-cadherin upregulation, impaired dissolution of the MES, and reduced cell migration for palatal fusion. The findings imply that miR-200c is essential in palatal fusion as it governs E-cadherin expression, cell death, and cell migration, acting as a non-coding RNA. This study may contribute to clarifying the underlying molecular mechanisms in palate formation and provides insights into potential gene therapies for cleft palate.

LI-RADS version 2018 for hepatocellular carcinoma < 1.0 cm on gadoxetate disodium-enhanced magnetic resonance imaging.

OBJECTIVES: We aimed to develop and evaluate a modified Liver Imaging Reporting and Data System (LI-RADS) version 2018 using significant ancillary features for diagnosing hepatocellular carcinoma (HCC) < 1.0 cm on gadoxetate disodium-enhanced magnetic resonance imaging (MRI). METHODS: Patients who underwent preoperative gadoxetate disodium-enhanced MRI for focal solid nodules < 2.0 cm within 1 month of MRI between January 2016 and December 2020 were retrospectively analyzed. Major and ancillary features were compared between HCCs of < 1.0 cm and 1.0-1.9 cm using the chi-square test. Significant ancillary features associated with HCC < 1.0 cm were determined by univariable and multivariable logistic regression analysis. The sensitivity and specificity of LR-5 were compared between LI-RADS v2018 and our modified LI-RADS (applying the significant ancillary feature) using generalized estimating equations. RESULTS: Of 796 included nodules, 248 were < 1.0 cm and 548 were 1.0-1.9 cm. HCC < 1.0 cm less frequently showed an enhancing capsule (7.1% vs. 31.1%, p < .001) and threshold growth (0% vs. 8.3%, p = .007) than HCC of 1.0-1.9 cm. Restricted diffusion was the only ancillary feature significant for diagnosing HCC < 1.0 cm (adjusted odds ratio = 11.50, p < .001). In the diagnosis of HCC, our modified LI-RADS using restricted diffusion had significantly higher sensitivity than LI-RADS v2018 (61.8% vs. 53.5%, p < .001), with similar specificity (97.3% vs. 97.8%, p = .157). CONCLUSION: Restricted diffusion was the only significant independent ancillary feature for diagnosing HCC < 1.0 cm. Our modified LI-RADS using restricted diffusion can improve the sensitivity for HCC < 1.0 cm. KEY POINTS: • The imaging features of hepatocellular carcinoma (HCC) < 1.0 cm differed from those of HCC of 1.0-1.9 cm. • Restricted diffusion was the only significant independent ancillary feature for HCC < 1.0 cm. • Modified Liver Imaging Reporting and Data System (LI-RADS) with the addition of restricted diffusion can improve the sensitivity for HCC < 1.0 cm.

Supraclavicular cephalic vein draining into the internal jugular vein via the external jugular vein.

PURPOSE: The aim of this study is to report rare anatomical variations of the cephalic vein (CV) in a 77-year-old Korean male cadaver. CASE REPORT: On the right upper arm, the CV located lateral to the deltopectoral groove passed anterior to the clavicle at the lateral one-fourth of the clavicle without anastomosis to the axillary vein. It was connected to the transverse cervical and suprascapular veins by two communicating branches in the middle of its course at the neck, and opened into the external jugular vein at its junction with the internal jugular veins. The suprascapular and anterior jugular veins were flowed into the subclavian vein at the jugulo-subclavian venous confluence, and were connected by a short communicating branch. CONCLUSION: Detailed knowledge of the variations in the CV is expected to be helpful in decreasing unpredicted injuries and possible postoperative complications when invasive venous access is performed through the CV.

Simplified LI-RADS for Hepatocellular Carcinoma Diagnosis at Gadoxetic Acid-enhanced MRI.

Background Although various modifications to the Liver Imaging Reporting and Data System (LI-RADS) at gadoxetic acid-enhanced MRI have been suggested, LI-RADS shows suboptimal sensitivity for hepatocellular carcinoma (HCC) and is perceived to be too complex. Purpose To evaluate clinical usefulness of a simplified LI-RADS for diagnosing HCCs of 30 mm or smaller at gadoxetic acid-enhanced MRI. Materials and Methods Patients who underwent gadoxetic acid-enhanced MRI examination and subsequent resection, transplantation, or biopsy for focal solid nodules of 30 mm or smaller between January 2019 and December 2020 at a single tertiary referral institution were retrospectively analyzed. Two strategies for simplified LI-RADS using one size criterion (≥10 mm) were evaluated (strategy A, using classifications for nodules of 10-19 mm for nodules both 10-19 mm and ≥20 mm; strategy B, using classifications for nodules ≥20 mm for nodules both 10-19 mm and ≥20 mm). Multivariable analysis was performed to determine significant ancillary features for HCC. Generalized estimating equations were used to compare diagnostic performance for LR-5 (definite HCC) between LI-RADS version 2018 and simplified LI-RADS. The time required for LI-RADS category assignment was compared between the two systems with use of a paired t test. Results A total of 645 nodules from 510 patients (mean age ± SD, 60 years ± 10; 393 men) were evaluated. Compared with strategy A, strategy B had a higher sensitivity of 74% (347 of 470 nodules [95% CI: 70, 78]) vs 73% (342 of 470 nodules [95% CI: 69, 77]) (P = .02) with the same specificity of 96% (168 of 175 nodules [95% CI: 92, 98]) vs 96% (168 of 175 nodules [95% CI: 92, 98]) (P > .99). In strategy B, transitional phase hypointensity was an independent ancillary feature for HCC (P = .04) in LR-4 of at least 10 mm with arterial phase hyperenhancement and no other major features. In all 645 nodules, simplified LI-RADS with use of both strategy B and transitional phase hypointensity had a higher sensitivity of 82% (387 of 470 nodules [95% CI: 79, 86]) vs 73% (343 of 470 nodules [95% CI: 69, 77]) (P < .001) than LI-RADS version 2018, without lower specificity (94%, 165 of 175 nodules [95% CI: 90, 97] vs 96%, 168 of 175 nodules [95% CI: 92, 98], P = .08). Compared with LI-RADS version 2018, simplified LI-RADS reduced the time for LI-RADS category assignment (44 seconds ± 23 vs 74 seconds ± 22, P < .001). Conclusion A simplified Liver Imaging Reporting and Data System was found to be clinically useful for diagnosing hepatocellular carcinomas of 30 mm or smaller at gadoxetic acid-enhanced MRI. © RSNA, 2022 Online supplemental material is available for this article.

Liver Imaging Reporting and Data System categories: Long-term imaging outcomes in a prospective surveillance cohort.

BACKGROUND AND AIMS: We assessed the imaging outcomes of Liver Imaging Reporting and Data System (LI-RADS) v2018 categories in prospective hepatocellular carcinoma (HCC) surveillance cohort and determined imaging features significantly predictive of progression to a malignant LI-RADS category. METHODS: The imaging outcomes of 120 patients (162 observations) prospectively enrolled between November 2011 and August 2012 were analysed according to LI-RADS v2018. Cumulative incidences for progression to a malignant category (LR-5 or LR-M) and LR-4 or higher were calculated for each baseline category and compared using log-rank tests. Clinical variables and imaging features significantly predictive of progression to a malignant category were evaluated using Cox proportional hazards modelling. RESULTS: The 162 observations were initially categorized into 60 LR-2, 75 LR-3 and 27 LR-4. For LR-4 observations, the 1-year, 3-year and 5-year cumulative incidences of progression to a malignant category were 18.5% (95% confidence interval, 6.6-35.2%), 43.0% (23.1-61.5%) and 52.5% (25.9-73.5%), which were significantly higher than those of LR-2 and LR-3 (p < .001). For LR-3, the 1-year, 3-year and 5-year cumulative incidences of progression to LR-4 or higher were 4.1% (1.1-10.4%), 13.9% (6.7-23.6%) and 23.1% (12.7-35.4%), which were significantly higher than that of LR-2 (p  = .009). In multivariable analysis, size ≥1.0 cm (hazard ratio [HR] = 2.58, 1.04-6.40) and nonrim arterial-phase hyperenhancement (HR = 2.45, 1.11-5.42) were significantly independently associated with progression to a malignant category. CONCLUSION: Long-term imaging outcomes differed significantly according to LI-RADS category. Size ≥1.0 cm and nonrim arterial-phase hyperenhancement were imaging features significantly predictive of progression to a malignant category.

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

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.

Thermal ablation in the treatment of intrahepatic cholangiocarcinoma: a systematic review and meta-analysis.

OBJECTIVE: To summarize the efficacy and safety of thermal ablation for the treatment of intrahepatic cholangiocarcinoma (ICC). METHODS: MEDLINE, EMBASE, Cochran Library, and Web of Science databases were searched for studies reporting outcomes in patients with ICC treated with thermal ablation. Meta-analyses of cumulative overall survival (OS) and recurrence-free survival (RFS), Kaplan-Meier survival rates according to time to local tumor progression (TTLTP), technical efficacy, and incidence of complications were analyzed. Pooled hazard ratios of common variables were calculated to explore factors associated with OS. RESULTS: Twenty observational studies comprising 917 patients were reviewed (primary ICC [n = 502]; post-surgical recurrent ICC [n = 355]; information not available [n = 60]). The pooled proportion of technical efficacy was 91.9% (95% CI, 87.3-94.9%). The pooled 1-, 3-, and 5-year OS rates were 82.4% (95% CI, 75.1-88.9%), 42.1% (95% CI, 36.0-48.4%), and 28.5% (95% CI, 21.2-36.2%). Primary tumors showed higher 3-year OS rates than recurrent ones, with borderline significance (p = 0.072). The pooled 1- and 3-year RFS rates were 40.0% (95% CI, 33.6-46.4%) and 19.2% (95% CI, 8.4-32.7%). The pooled 1-, 3-, and 5-year TTLTP rates were 79.3% (95% CI, 65.1-90.9%), 59.5% (95% CI, 49.1-69.4%), and 58.2% (95% CI, 44.9-70.9%). The pooled incidence of major complications was 5.7% (95% CI, 4.1-7.8%). Tumor size (> 3 cm), multiple tumors, and age (> 65 years) were factors associated with shorter OS. CONCLUSION: Thermal ablation is a successful alternative with a good safety profile, especially for a single ICC smaller than 3 cm. KEY POINTS: • The pooled 1-, 3-, and 5-year OS rates following thermal ablation for the treatment of intrahepatic cholangiocarcinoma were 82.4%, 42.1%, and 28.5%. • The pooled incidence of major complications was 5.7%. • A tumor size > 3 cm (HR: 2.12, p = 0.006), multiple tumors (HR: 1.67, p = 0.004), and age > 65 years (HR: 1.67, p = 0.006) were factors associated with shorter OS.

Hypervascular transformation of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement on gadoxetic acid-enhanced MRI: long-term follow-up in a surveillance cohort.

OBJECTIVES: With the increasing use of gadoxetic acid-enhanced MRI for HCC surveillance, hepatobiliary phase (HBP) hypointense nodules without arterial phase hyperenhancement (APHE) are frequently encountered. We investigated the rate of these nodules with hypervascular transformation, which suggests hepatocarcinogenesis, by using a prospectively collected longitudinal surveillance cohort data. METHODS: This study included 382 prospectively enrolled patients at high risk for developing HCC who underwent 1-3 rounds of bi-annual surveillance gadoxetic acid-enhanced MRI. MRI was analyzed to detect HBP hypointense nodules without APHE. Follow-up dynamic CTs and MRIs were evaluated to detect hypervascular transformation of the nodules. Cox proportional hazards regression analyses were used to find predictors for hypervascular transformation. RESULTS: A total of 76 HBP hypointense nodules without APHE were found in 48 patients, giving a prevalence of 12.6% (48/382). The mean nodule size was 10.8 mm, with 43.4% (33/76) being ≥ 10 mm. Over a median follow-up of 78.6 months, 19 nodules (25.0%) showed hypervascular transformation, all of which demonstrated typical imaging features of HCC. On multivariable Cox-regression analysis, size (≥ 10 mm) was the only independent predictor of hypervascular transformation (hazard ratio, 3.31; 95% confidence interval, 1.21-9.05). The cumulative incidence of hypervascular transformation at 12 and 60 months of nodules ≥ 10 mm was 12.3% and 50.4%, respectively, while that of nodules < 10 mm was 2.5% and 13.9%, respectively. CONCLUSIONS: About half of the HBP hypointense nodules ≥ 10 mm without APHE transformed to HCC at 5 years of follow-up, indicating the necessity for cautious monitoring with an augmented and extended follow-up schedule for these nodules. KEY POINTS: • The prevalence of HBP hypointense nodules without APHE was 12.6% in a prospectively recruited population at high risk of developing HCC. • Nodule size ≥ 10 mm was significantly associated with hypervascular transformation, and approximately half of the HBP hypointense nodules ≥ 10 mm without APHE transformed to HCC during 5 years of follow-up. • Given the risk of malignant transformation, HBP hypointense nodules ≥ 10 mm without APHE should be closely monitored.

Classification of the interosseous tarsometatarsal ligaments of the foot.

BACKGROUND: The aim of this study was to clarify the anatomical features of the interosseous tarsometatarsal ligaments of foot and to classify their types based on the combinations of their ligamentous components. METHODS: Fifty feet from 27 adult Korean cadavers were dissected. RESULTS: The interosseous tarsometatarsal ligaments were observed in the first, second, and third cuneometatarsal joint spaces. The interosseous tarsometatarsal ligament of the first cuneometatarsal space consistently connected the medial cuneiform and the second metatarsal, and was accompanied by one or two accessory ligaments above (34%) and/or below (6%) the Lisfranc ligament. The interosseous tarsometatarsal ligaments of the second and third cuneometatarsal joint spaces comprised seven and five components, and were classified into five and three types depending on the number and combination of the components, respectively. CONCLUSIONS: These results are expected to advance the current knowledge on the tarsometatarsal joint and provide helpful information for more accurate and successful diagnosis and treatment of lesions at this joint.

Percutaneous Radiofrequency Ablation for Recurrent Intrahepatic Cholangiocarcinoma After Curative Resection: Multivariable Analysis of Factors Predicting Survival Outcomes.

OBJECTIVE. The purpose of this study was to evaluate the factors associated with local tumor progression (LTP) and overall survival (OS) in patients who have undergone percutaneous radiofrequency ablation (RFA) for recurrent intrahepatic cholangiocarcinoma (iCCA) after curative resection. MATERIALS AND METHODS. Data from 40 patients (mean age, 56.3 years) with 64 recurrent iCCAs (median diameter, 1.5 cm) who underwent percutaneous RFA between 1999 and 2019 were retrospectively analyzed. Patients were included if they had three or fewer metastases, a maximum tumor diameter of 5 cm or less, and disease confined to the liver. RESULTS. Technical success was achieved in all patients, with no procedure-related mortality. During follow-up, local progression of treated lesions was observed in 31.3% of tumors. The median OS and 5-year survival rate from initial RFA were 26.6 months and 18.3%, respectively. Multivariable analysis showed that a larger tumor diameter (> 2 cm, p = .004) was significantly associated with reduced LTP-free survival and that both a larger tumor diameter and less than 1 year from surgery to recurrence (p = .005 and .006, respectively) were statistically significant predictors of reduced OS after RFA. CONCLUSION. Percutaneous RFA may offer a well-tolerated and successful approach to local tumor control in patients with recurrent iCCA after curative surgery. Patients with a small-diameter tumor (≤ 2 cm) and late hepatic recurrence (≥ 1 year after curative resection) benefited most from RFA treatment.

Enhanced production of clavulanic acid by improving glycerol utilization using reporter-guided mutagenesis of an industrial Streptomyces clavuligerus strain.

Clavulanic acid (CA) produced by Streptomyces clavuligerus is a clinically important ß-lactamase inhibitor. It is known that glycerol utilization can significantly improve cell growth and CA production of S. clavuligerus. We found that the industrial CA-producing S. clavuligerus strain OR generated by random mutagenesis consumes less glycerol than the wild-type strain; we then developed a mutant strain in which the glycerol utilization operon is overexpressed, as compared to the parent OR strain, through iterative random mutagenesis and reporter-guided selection. The CA production of the resulting S. clavuligerus ORUN strain was increased by approximately 31.3% (5.21 ± 0.26 g/l) in a flask culture and 17.4% (6.11 ± 0.36 g/l) in a fermenter culture, as compared to that of the starting OR strain. These results confirmed the important role of glycerol utilization in CA production and demonstrated that reporter-guided mutant selection is an efficient method for further improvement of randomly mutagenized industrial strains.

Anatomic variations of the intrathoracic nerves and the neural connections of the second and third thoracic sympathetic ganglia to the brachial plexus.

INTRODUCTION: This study investigated morphological variations of the intrathoracic nerves and the neural connections of the second and third thoracic sympathetic ganglia to the brachial plexus based on the existence of the intrathoracic nerves and the rami communicantes. MATERIALS AND METHODS: Fifty thoracic sympathetic trunks from 26 Korean adult cadavers were used. RESULTS: The first intrathoracic nerve connecting the first and second thoracic nerves was observed on 36 sides (72%), and the second intrathoracic nerve connecting the second and third thoracic nerves was found on three sides (6%). There were either one (62%) or two (10%) first intrathoracic nerves, and only one second intrathoracic nerve (6%). The neural connections of the second and third thoracic sympathetic ganglia to the first thoracic nerve were classified into three types based on the existence of the intrathoracic nerves: Type I (68%) had only the first intrathoracic nerve, Type II (26%) had no intrathoracic nerve, and Type III (6%) had both the first and second intrathoracic nerves. Types I, II, and III were further subdivided into 10, 6, and 3 types, respectively, according to the types of the rami communicantes arising from the second and third thoracic sympathetic ganglia. CONCLUSIONS: Improved knowledge of the variations in intrathoracic nerves and upper thoracic sympathetic ganglia will be helpful to thoracic surgeons when they are disrupting the sympathetic supply to the hand for treating palmar hyperhidrosis, and contribute to successful diagnoses and treatments.

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

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.

Liver imaging reporting and data system category M: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The Liver Imaging Reporting and Data System (LI-RADS) category M (LR-M) was introduced to preserve the high specificity of LI-RADS algorithm for diagnosing hepatocellular carcinoma (HCC). We aimed to systematically determine the probability of the LR-M for HCC and non-HCC malignancy, and to determine the sources of heterogeneity between reported results. METHODS: Original studies reporting the probability of LR-M for HCC and non-HCC malignancy on magnetic resonance imaging (MRI) were identified in MEDLINE and EMBASE. The meta-analytic pooled percentages of HCC and non-HCC in LR-M were calculated. Meta-regression analysis was performed to explore study heterogeneity. The meta-analytic frequency of each LR-M imaging feature was determined. RESULTS: We found 10 studies reporting the diagnostic performance of LR-M (1819 lesions in 1631 patients), and six reporting the frequency of LR-M imaging features. The pooled percentages of HCC and non-HCC malignancy for LR-M were 28.2% (95% confidence interval [CI], 23.8%-33.1%; I2  = 83%) and 69.6% (95% CI, 64.6%-74.1%; I2  = 83%) respectively. The study type and MRI scanner field strength were significantly associated with study heterogeneity (P ≤ .04). Of the seven imaging features, rim arterial phase hyperenhancement showed the highest frequency in both non-HCC (48.9%; 95% CI, 43.0%-54.8%) and HCC groups (9.8%; 95% CI, 6.9%-13.6%). CONCLUSIONS: The LR-M category most commonly included non-HCC malignancy but also included 28.2% of HCC. Substantial study heterogeneity was noted, and it was significantly associated with study type and MRI scanner field strength. In addition, the frequency of LR-M imaging features was variable.

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

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.