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.

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.

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).

Transcriptome profiles of Streptomyces clavuligerus strains producing different titers of clavulanic acid.

Streptomyces clavuligerus NRRL 3585 is a native producer of clavulanic acid (CA), a clinically used ß-lactamase inhibitor, and is widely used as an industrial strain for the production of antibiotics. Selective random mutagenesis has successfully generated the improved CA-producing S. clavuligerus mutant strains as well as the strain with the loss of CA biosynthesis. To understand the molecular mechanisms associated with the improved CA-production potential, genome-scale RNA-sequencing-based transcriptional data were obtained for the wild-type S. clavuligerus strain and its three mutant strains. Total RNA samples for each strain were collected across four different growth stages, and all 32 sequencing data points exhibited an average Phred score of 36. The high-quality genome-scale transcriptional profile of S. clavuligerus strains with varied CA biosynthetic potential provides valuable insights and new opportunities for discovering efficient metabolic engineering strategies for the development of improved industrial strains.

Liver Imaging Reporting and Data System version 2018 for diagnosing hepatocellular carcinoma in alcoholic liver cirrhosis and virus-related cirrhosis.

PURPOSE: We aimed to evaluate and compare the diagnostic performance of Liver Imaging Reporting and Data System (LI-RADS) v2018 for hepatocellular carcinoma (HCC) ≤ 3.0 cm on gadoxetic acid-enhanced MRI according to the etiology of cirrhosis. METHODS: Thirty-eight patients with alcoholic liver cirrhosis (ALC) and 37 with hepatitis C virus-related cirrhosis (HCV) who underwent preoperative MRI and subsequent surgical resection or transplantation were included. For comparison groups, patients with hepatitis B virus-related cirrhosis (HBV) were included by 1:1 matching with HCV and ALC groups according to age, lesion size, and Child-Pugh classification. The imaging characteristics of background liver and focal lesions were analyzed. The diagnostic performance of LI-RADS was compared between HCV and HBV groups, and between ALC and HBV groups. RESULTS: ALC group showed significantly higher frequency of hepatic steatosis (25.8 % vs. 6.1 %, p =.04) and lower frequency of nonperipheral washout on portal venous-phase in HCC (63.2 % vs. 97.1 %, p <.001) compared with HBV group. ALC group showed significantly lower sensitivity than HBV group (52.6 % vs. 88.6 %, p<.001). No significant differences in diagnostic performance were found between HCV and HBV groups. In ALC group, hepatobiliary-phase hypointensity provided significantly higher sensitivity (76.3 % vs. 52.6 %, p =.008). CONCLUSION: The sensitivity of LI-RADS for diagnosing HCC ≤ 3.0 cm was significantly lower in the ALC group than in the HBV group.

Gene Regulatory Networks and Signaling Pathways in Palatogenesis and Cleft Palate: A Comprehensive Review.

Palatogenesis is a complex and intricate process involving the formation of the palate through various morphogenetic events highly dependent on the surrounding context. These events comprise outgrowth of palatal shelves from embryonic maxillary prominences, their elevation from a vertical to a horizontal position above the tongue, and their subsequent adhesion and fusion at the midline to separate oral and nasal cavities. Disruptions in any of these processes can result in cleft palate, a common congenital abnormality that significantly affects patient's quality of life, despite surgical intervention. Although many genes involved in palatogenesis have been identified through studies on genetically modified mice and human genetics, the precise roles of these genes and their products in signaling networks that regulate palatogenesis remain elusive. Recent investigations have revealed that palatal shelf growth, patterning, adhesion, and fusion are intricately regulated by numerous transcription factors and signaling pathways, including Sonic hedgehog (Shh), bone morphogenetic protein (Bmp), fibroblast growth factor (Fgf), transforming growth factor beta (Tgf-ß), Wnt signaling, and others. These studies have also identified a significant number of genes that are essential for palate development. Integrated information from these studies offers novel insights into gene regulatory networks and dynamic cellular processes underlying palatal shelf elevation, contact, and fusion, deepening our understanding of palatogenesis, and facilitating the development of more efficacious treatments for cleft palate.

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.

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.

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.

Functional Reaction Times of a Simulated Blocking Test among Para Taekwondo Athletes.

Para taekwondo is a combat sport martial art that requires fast reaction times for successful defense during fighting. The current classification system is based on the function and the effective length of the upper limbs, which affects the athlete's ability to block. Therefore, this study aimed to investigate the differences between the different classes in the athlete's ability to block and move around the ring. A total of 87 Para taekwondo (K42, K43, and K44) athletes' data were analyzed. Each participant engaged in the blocking reaction time test in a fighting stance with the left leg in front, the right leg in front, and the legs parallel in random order. A foot-stepping reaction test was performed to anlyze how the athletes moved in various directions. The results indicated no significant differences between the classes for the lower body foot stepping reaction times and the upper body blocking performance times. The stimulated blocking time of the Para taekwondo athletes ranged from 0.79 to 0.97 s Furthermore, the neurological group (0.86 ± 0.09 s) was significantly slower than the amputation/dysmelia group (0.81 ± 0.07 s). We thus concluded that the neurologically impaired athletes were disadvantaged and therefore belonged in a separate class.

New strategy for Liver Imaging Reporting and Data System category M to improve diagnostic performance of MRI for hepatocellular carcinoma ≤ 3.0 cm.

PURPOSE: We aimed to determine a new strategy for Liver Imaging Reporting and Data System category M (LR-M) criteria to improve the diagnosis of HCC ≤ 3.0 cm on magnetic resonance imaging (MRI). METHODS: A total of 463 pathologically confirmed hepatic observations ≤ 3.0 cm (375 HCCs, 32 other malignancies, 56 benignities) in 384 patients at risk of HCC who underwent gadoxetate-enhanced MRI were retrospectively analyzed. Two radiologists evaluated the presence of major, ancillary, and LR-M features according to LI-RADS v2018. Of the ten LR-M features, those significantly associated with non-HCC malignancy were identified using multivariable logistic regression analysis, and new LR-M criteria for improving the diagnosis of HCC were investigated. Generalized estimating equations were used to compare sensitivity and specificity of LR-5 for diagnosing HCC using the new LR-M criteria with values calculated using the original LR-M criteria. p < 0.05 was considered to indicate a significant difference. RESULTS: Of ten LR-M features, rim arterial-phase hyperenhancement, delayed central enhancement, targetoid restriction, and targetoid transitional-phase/hepatobiliary-phase appearance were independently significantly associated with non-HCC malignancy (adjusted odds ratio ≥ 6.2; p ≤ 0.02). Using the new LR-M criteria (two or more of these significant features), the sensitivity of LR-5 for diagnosing HCC was higher than that with the original LR-M criteria (69% [95% confidence interval 64-73%] vs. 65% [61-70%], p = 0.002), whereas the specificity was similar (90% [82-95%] vs. 92% [83-96%], p = 0.28). CONCLUSION: The new LR-M criteria (two or more significant features) can improve the sensitivity of LR-5 for diagnosing HCC ≤ 3.0 cm, without compromising specificity.

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.

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.

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.

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.

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.