Upregulation of the ERRγ-VDAC1 axis underlies the molecular pathogenesis of pancreatitis.

Emerging evidence suggest that transcription factors play multiple roles in the development of pancreatitis, a necroinflammatory condition lacking specific therapy. Estrogen-related receptor γ (ERRγ), a pleiotropic transcription factor, has been reported to play a vital role in pancreatic acinar cell (PAC) homeostasis. However, the role of ERRγ in PAC dysfunction remains hitherto unknown. Here, we demonstrated in both mice models and human cohorts that pancreatitis is associated with an increase in ERRγ gene expression via activation of STAT3. Acinar-specific ERRγ haploinsufficiency or pharmacological inhibition of ERRγ significantly impaired the progression of pancreatitis both in vitro and in vivo. Using systematic transcriptomic analysis, we identified that voltage-dependent anion channel 1 (VDAC1) acts as a molecular mediator of ERRγ. Mechanistically, we showed that induction of ERRγ in cultured acinar cells and mouse pancreata enhanced VDAC1 expression by directly binding to specific site of the Vdac1 gene promoter and resulted in VDAC1 oligomerization. Notably, VDAC1, whose expression and oligomerization were dependent on ERRγ, modulates mitochondrial Ca2+ and ROS levels. Inhibition of the ERRγ-VDAC1 axis could alleviate mitochondrial Ca2+ accumulation, ROS formation and inhibit progression of pancreatitis. Using two different mouse models of pancreatitis, we showed that pharmacological blockade of ERRγ-VDAC1 pathway has therapeutic benefits in mitigating progression of pancreatitis. Likewise, using PRSS1R122H-Tg mice to mimic human hereditary pancreatitis, we demonstrated that ERRγ inhibitor also alleviated pancreatitis. Our findings highlight the importance of ERRγ in pancreatitis progression and suggests its therapeutic intervention for prevention and treatment of pancreatitis.

Maximizing Photoelectrochemical Performance in Metal-Oxide Hybrid Composites via Amorphous Exsolution-A New Exsolution Mechanism for Heterogeneous Catalysis.

Exsolution generates metal nanoparticles anchored within crystalline oxide supports, ensuring efficient exposure, uniform dispersion, and strong nanoparticle-perovskite interactions. Increased doping level in the perovskite is essential for further enhancing performance in renewable energy applications; however, this is constrained by limited surface exsolution, structural instability, and sluggish charge transfer. Here, hybrid composites are fabricated by vacuum-annealing a solution containing SrTiO3 photoanode and Co cocatalyst precursors for photoelectrochemical water-splitting. In situ transmission electron microscopy identifies uniform, high-density Co particles exsolving from amorphous SrTiO3 films, followed by film-crystallization at elevated temperatures. This unique process extracts entire Co dopants with complete structural stability, even at Co doping levels exceeding 30%, and upon air exposure, the Co particles embedded in the film oxidize to CoO, forming a Schottky junction at the interface. These conditions maximize photoelectrochemical activity and stability, surpassing those achieved by Co post-deposition and Co exsolution from crystalline oxides. Theoretical calculations demonstrate in the amorphous state, dopant─O bonds become weaker while Ti─O bonds remain strong, promoting selective exsolution. As expected from the calculations, nearly all of the 30% Fe dopants exsolve from SrTiO3 in an H2 environment, despite the strong Fe─O bond's low exsolution tendency. These analyses unravel the mechanisms driving the amorphous exsolution.

Intraindividual comparison of prognostic imaging features of HCCs between MRIs with extracellular and hepatobiliary contrast agents.

BACKGROUND & AIMS: Accumulating evidence suggests that certain imaging features of hepatocellular carcinoma (HCC) may have prognostic implications. This study aimed to intraindividually compare MRIs with extracellular contrast agent (ECA-MRI) and hepatobiliary agent (HBA-MRI) for prognostic imaging features of HCC and to compare the prediction of microvascular invasion (MVI) and early recurrence between the two MRIs. METHODS: The present study included 102 prospectively enrolled at-risk patients (median age, 61.0 years; 83 men) with surgically resected single HCC with both preoperative ECA-MRI and HBA-MRI between July 2019 and June 2023. The McNemar test was used to compare each prognostic imaging feature between the two MRIs. Significant imaging features associated with MVI were identified by multivariable logistic regression analysis, and early recurrence rates (<2 years) were compared between the two MRIs. RESULTS: The frequencies of prognostic imaging features were not significantly different between the two MRIs (p = .07 to >.99). Non-smooth tumour margin (ECA-MRI, odds ratio [OR] = 5.30; HBA-MRI, OR = 7.07) and peritumoral arterial phase hyperenhancement (ECA-MRI, OR = 4.26; HBA-MRI, OR = 4.43) were independent factors significantly associated with MVI on both MRIs. Two-trait predictor of venous invasion (presence of internal arteries and absence of hypoattenuating halo) on ECA-MRI (OR = 11.24) and peritumoral HBP hypointensity on HBA-MRI (OR = 20.42) were other predictors of MVI. Early recurrence rates of any two or more significant imaging features (49.8% on ECA-MRI vs 51.3% on HBA-MRI, p = .75) were not significantly different between the two MRIs. CONCLUSION: Prognostic imaging features of HCC may be comparable between ECA-MRI and HBA-MRI.

Prediction of tumor recurrence after surgical resection of ampullary adenocarcinoma using magnetic resonance imaging.

OBJECTIVES: To predict tumor recurrence in patients who underwent surgical resection of ampullary adenocarcinoma using preoperative magnetic resonance (MR) imaging findings combined with clinical findings. METHODS: In this multicenter study, a total of 113 patients (mean age, 62.9 ± 9.8 years; 58 men and 55 women) with ampullary adenocarcinoma who underwent preoperative MR imaging and surgery with margin-negative resection between 2006 and 2017 were retrospectively included. The MR imaging findings were evaluated by two radiologists. Preoperative clinical findings were obtained. Cox proportional regression analyses were used to identify the independent prognostic factors for recurrence-free survival (RFS). A nomogram was created based on the multivariable analysis and was internally validated. RESULTS: Multivariable analysis revealed that presence of infiltrative tumor margin (hazard ratio [HR]: 2.18, p = 0.019), adjacent organ invasion (HR: 3.31, p = 0.006), adjacent vessel invasion (HR: 5.42, p = 0.041), peripancreatic lymph node enlargement (HR: 2.1, p = 0.019), and jaundice (HR: 1.93, p = 0.043) were significantly associated with worse RFS of ampullary adenocarcinoma after surgical resection. These MR imaging and clinical findings were used to construct a nomogram. On internal validation, the calibration plots showed excellent agreement between the predicted probabilities and the actual rates of tumor recurrence, with Harrell's c-index of 0.746. CONCLUSIONS: Combination of preoperative MR imaging and clinical findings can be useful for predicting tumor recurrence after surgical resection of ampullary adenocarcinoma. Identifying these features before surgery may aid in better treatment planning and management of these patients. CLINICAL RELEVANCE STATEMENT: A predictive nomogram using preoperative MR imaging and clinical findings can be useful in estimating the recurrence-free survival after surgical resection of ampullary adenocarcinoma. KEY POINTS: • Presently, tumor size on imaging is the only non-invasive factor that correlates with recurrence-free survival from ampullary adenocarcinoma; other factors are obtained postoperatively. • Infiltrative tumor margin, adjacent organ invasion, adjacent vessel invasion, peripancreatic lymph node enlargement on MRI, and jaundice are significant predictors for recurrence. • A nomogram incorporating significant MR imaging and clinical findings showed good performance in predicting recurrence-free survival, which can help in treatment planning.

Sargachromenol Attenuates Inflammatory Responses by Regulating NF-κB and Nrf2 Pathways in RAW 264.7 Cells and LPS-treated Mice.

This study aims to explore the anti-inflammatory mechanisms of sargachromenol in both RAW 264.7 cells and lipopolysaccharide (LPS)-treated mice, as previous reports have suggested that sargachromenol possesses anti-aging, anti-inflammatory, antioxidant, and neuroprotective properties. Although the precise mechanism behind its anti-inflammatory activity remains unclear, pretreatment with sargachromenol effectively reduced the production of nitric oxide, prostaglandin E2, and interleukin (IL)-1ß in LPS-stimulated RAW 264.7 cells by inhibiting cyclooxygenase-2. Moreover, sargachromenol inhibited the activation of nuclear factor-κB (NF-κB) by preventing the degradation of the inhibitor of κB-α (IκB-α) and inhibiting protein kinase B (Akt) phosphorylation in LPS-stimulated cells. We also found that sargachromenol induced the production of heme oxygenase-1 (HO-1) by activating the nuclear transcription factor erythroid-2-related factor 2 (Nrf2). In LPS-treated mice, oral administration of sargachromenol effectively reduced the levels of IL-1ß, IL-6, and tumor necrosis factor-α (TNF-α) in the serum, suggesting its ability to suppress the production of inflammatory mediators by inhibiting the Akt/NF-κB pathway and upregulating the Nrf2/HO-1 pathway.

Inhibition of pyruvate dehydrogenase kinase 4 ameliorates kidney ischemia-reperfusion injury by reducing succinate accumulation during ischemia and preserving mitochondrial function during reperfusion.

Ischemia-reperfusion (IR) injury, a leading cause of acute kidney injury (AKI), is still without effective therapies. Succinate accumulation during ischemia followed by its oxidation during reperfusion leads to excessive reactive oxygen species (ROS) and severe kidney damage. Consequently, the targeting of succinate accumulation may represent a rational approach to the prevention of IR-induced kidney injury. Since ROS are generated primarily in mitochondria, which are abundant in the proximal tubule of the kidney, we explored the role of pyruvate dehydrogenase kinase 4 (PDK4), a mitochondrial enzyme, in IR-induced kidney injury using proximal tubule cell-specific Pdk4 knockout (Pdk4ptKO) mice. Knockout or pharmacological inhibition of PDK4 ameliorated IR-induced kidney damage. Succinate accumulation during ischemia, which is responsible for mitochondrial ROS production during reperfusion, was reduced by PDK4 inhibition. PDK4 deficiency established conditions prior to ischemia resulting in less succinate accumulation, possibly because of a reduction in electron flow reversal in complex II, which provides electrons for the reduction of fumarate to succinate by succinate dehydrogenase during ischemia. The administration of dimethyl succinate, a cell-permeable form of succinate, attenuated the beneficial effects of PDK4 deficiency, suggesting that the kidney-protective effect is succinate-dependent. Finally, genetic or pharmacological inhibition of PDK4 prevented IR-induced mitochondrial damage in mice and normalized mitochondrial function in an in vitro model of IR injury. Thus, inhibition of PDK4 represents a novel means of preventing IR-induced kidney injury, and involves the inhibition of ROS-induced kidney toxicity through reduction in succinate accumulation and mitochondrial dysfunction.

Steatotic hepatocellular carcinoma: Association of MRI findings to underlying liver disease and clinicopathological characteristics.

BACKGROUND & AIMS: Fatty change is commonly observed in hepatocellular carcinoma (HCC); however, the characteristics of steatotic and steatohepatitic HCCs are not well understood. METHODS: This retrospective study included patients with HCCs who underwent resection between January 2014 and December 2019 to evaluate clinicopathological and magnetic resonance imaging features. Tumours were categorized as magnetic resonance imaging-steatotic, pathology-steatotic and steatohepatitic HCCs and were defined as HCCs with ≥50% steatosis on in-and-oppose phase images, ≥34% tumour cells with lipid droplets and ≥50% tumour areas with steatohepatitic features on light microscopy respectively. RESULTS: Of 465 HCCs, 38 (8%), 23 (5%) and 15 (3%) were diagnosed as magnetic resonance imaging-steatotic, pathology-steatotic and steatohepatitic HCCs respectively. These HCC variants were less likely to be associated with hepatitis B virus infections than with type 2 diabetes mellitus, metabolic syndrome, non-tumour liver steatosis and steatohepatitis. Moreover, microvascular invasion was less likely to be associated with them than either tumour size or differentiation. Type 2 diabetes and non-tumour steatosis were independent risk factors for magnetic resonance imaging-steatotic HCCs. Pathology-steatotic HCCs and steatohepatitic HCCs were significantly associated with magnetic resonance imaging-steatotic HCCs. A targetoid appearance in the transitional or hepatobiliary phase was also more prevalent in steatohepatitic-HCCs than in non-steatohepatitic-HCCs. When magnetic resonance imaging-steatotic HCCs were combined with one or more ancillary features, the sensitivity and specificity were 60% and 97% respectively. CONCLUSION: Underlying fatty liver disease and metabolic syndrome are strongly associated with both steatotic and steatohepatitic HCCs. Clinicoradiological characteristics help identify steatohepatitic HCC with high specificity.

Preoperative computed tomography assessment of circumferential resection margin in retroperitonealized colon cancer predicts disease-free survival.

OBJECTIVES: The aim of this retrospective study was to predict circumferential resection margin (CRM) involvement on preoperative CT, and prognostic impact of CRM assessment by CT (ctCRM) in patients with retroperitonealized colon cancer. METHODS: This study included patients who underwent resection for ascending or descending colon cancer between July 2010 and February 2013. Positive ctCRM was defined as tumor distance to the retromesenteric plane of ≤ 1 mm. The origin of positive CRM was divided into primary tumor or other tumor components including lymph nodes, tumor deposits, or extramural venous invasions. Logistic regression analysis was performed to identify preoperative factors to predict pathologic CRM (pCRM). A Cox proportional hazards model was used in multivariable analysis to determine the preoperative factors affecting disease-free survival (DFS). RESULTS: A total of 274 patients (mean age, 64.0 years ± 11.0 [standard deviation]; 157 men) with retroperitonealized colon cancer were evaluated. Of 274 patients, 67 patients (24.5%) had positive CRM on surgical pathology. The accuracy of preoperative CT in predicting pCRM was 79.6% (218/274). Among preoperative factors, only CRM assessment on CT was independently associated with pCRM (p < 0.001). Positive ctCRM by primary tumor was an independent factor for DFS (HR, 3.362 [1.714-6.593]) and systemic recurrence (HR, 3.715 [1.787-7.724], but not for local recurrence on multivariable analyses. CONCLUSIONS: Preoperative CT can accurately predict pCRM, and positive ctCRM by primary tumor is an independent risk factor for DFS and systemic recurrence, but not for local recurrence in retroperitonealized colon cancer. KEY POINTS: • Preoperative CT can predict pathologic circumferential resection margin (CRM) with approximately 80% of accuracy in patients with retroperitonealized colon cancer. • Positive CRM by a primary tumor on preoperative CT is a poor prognostic factor for disease-free survival and systemic recurrence in patients with retroperitonealized colon cancer. • CRM involvement on CT was not associated with local recurrence in patients with retroperitonealized colon cancer.

Validation of the simplified magnetic resonance index of activity by using DWI without gadolinium enhancement to evaluate bowel inflammation in Crohn's disease.

OBJECTIVES: To validate the modified simplified magnetic resonance index of activity (sMARIA) score using DWI on non-contrast magnetic resonance enterography (MRE) to evaluate active inflammation in patients with Crohn's disease (CD), compared to the original sMARIA scoring system, with and without contrast enhancement. METHODS: This retrospective study included 275 bowel segments from 55 CD patients who underwent ileocolonoscopy and MRE within a 2-week period. Two blinded radiologists evaluated original sMARIA on both conventional MRE (CE-sMARIA) and non-contrast MRE (T2-sMARIA). Modified sMARIA was then evaluated using non-contrast MRE, replacing ulcerations with DWI grades. Three scoring systems were compared for diagnostic accuracy of active inflammation, correlation with simple endoscopic score (SES)-CD, and interobserver reproducibility. RESULTS: The AUC of modified sMARIA for detecting active inflammation (0.863, 95% confidence interval [0.803-0.923]) was significantly higher than T2-sMARIA (0.827 [0.773-0.881], p = 0.017), and comparable to CE-sMARIA (0.908 [0.857-0.959], p = 0.122). CE-sMARIA, T2-sMARIA, and modified sMARIA all showed moderate correlation with SES-CD (r = 0.795, 0.722, and 0.777, respectively). Interobserver reproducibility of diffusion restriction (κ, 0.686 [0.602-0.770]) was significantly better than ulcers on conventional MRE (κ, 0.382 [0.212-0.552]; p = 0.001) and T2-weighted image (κ, 0.312 [0.034-0.590]; p = 0.012). CONCLUSIONS: Modified sMARIA using DWI can improve the diagnostic performance of sMARIA on non-contrast MRE, showing comparable performance to sMARIA using contrast-enhanced MRE. KEY POINTS: • DWI can improve the diagnostic performance of non-contrast magnetic resonance enterography (MRE) for assessing active inflammation in patients with Crohn's disease. • Modified simplified magnetic resonance index of activity (sMARIA) using DWI grades in place of ulcers showed comparable diagnostic performance to sMARIA using conventional MRE with contrast-enhanced sequences.

Comparison of imaging findings of macrotrabecular-massive hepatocellular carcinoma using CT and gadoxetic acid-enhanced MRI.

OBJECTIVES: To investigate the imaging findings of macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) on CT and MRI, and examine their diagnostic performance and prognostic significance. METHODS: We retrospectively enrolled 220 consecutive patients who underwent hepatic resection between June 2009 and December 2013 for single treatment-naïve HCC, who have preoperative CT and gadoxetic acid-enhanced MRI. Independent reviews of histopathology and imaging were performed by two reviewers. Previously reported imaging findings, LI-RADS category, and CT attenuation of MTM-HCC were investigated. The diagnostic performance of the MTM-HCC diagnostic criteria was compared across imaging modalities. RESULTS: MTM-HCC was associated with ≥ 50% arterial phase hypovascular component, intratumoral artery, arterial phase peritumoral enhancement, and non-smooth tumor margin on CT and MRI (p < .05). Arterial phase hypovascular components were less commonly observed on MRI subtraction images than on CT or MRI, while non-rim arterial phase hyperenhancement and LR-5 were more commonly observed on MRI subtraction images than on MRI (p < .05). MTM-HCC showed lower tumor attenuation in the CT arterial phase (p = .01). Rhee's criteria, defined as ≥ 50% hypovascular component and ≥ 2 ancillary findings (intratumoral artery, arterial phase peritumoral enhancement, and non-smooth tumor margin), showed similar diagnostic performance for MRI (sensitivity, 41%; specificity, 97%) and CT (sensitivity, 31%; specificity, 94%). Rhee's criteria on CT were independent prognostic factors for overall survival. CONCLUSION: The MRI diagnostic criteria for MTM-HCC are applicable on CT, showing similar diagnostic performance and prognostic significance. For MTM-HCC, arterial phase subtraction images can aid in the HCC diagnosis by depicting subtle arterial hypervascularity. KEY POINTS: • MTM-HCC on CT demonstrated previously described MRI findings, including arterial phase hypovascular component, intratumoral artery, arterial phase peritumoral enhancement, and necrosis. • The MRI diagnostic criteria for MTM-HCC were also applicable to CT, showing comparable diagnostic performance and prognostic significance. • On arterial phase subtraction imaging, MTM-HCC more frequently demonstrated non-rim enhancement and LR-5 and less frequently LR-M than MRI arterial phase, which may aid in the diagnosis of HCC.

Optimal imaging criteria and modality to determine Milan criteria for the prediction of post-transplant HCC recurrence after locoregional treatment.

OBJECTIVES: We aimed to investigate the optimal radiologic method to determine Milan criteria (MC) for the prediction of recurrence in patients who underwent locoregional treatment (LRT) for hepatocellular carcinoma (HCC) and subsequent liver transplantation (LT). METHODS: This retrospective study included 121 HCC patients who underwent LRT and had both liver dynamic CT and MRI. They were classified with MC using four cross combinations of two imaging modalities (CT and MRI) and two diagnostic criteria (modified Response Evaluation Criteria in Solid Tumors [mRECIST] and Liver Imaging Reporting and Data System treatment response algorithm [LI-RADS TRA]). Competing risk regression was performed to analyze the time to recurrence after LT. The predictive abilities of the four methods for recurrence were evaluated using the time-dependent area under the curve (AUC). RESULTS: Competing risk regression analyses found that beyond MC determined by MRI with mRECIST was independently associated with recurrence (hazard ratio, 6.926; p = 0.001). With mRECIST, MRI showed significantly higher AUCs than CT at 3 years and 5 years after LT (0.597 vs. 0.756, p = 0.012 at 3 years; and 0.588 vs. 0.733, p = 0.024 at 5 years). Using the pathologic reference standard, MRI with LI-RADS TRA showed higher sensitivity (61.5%) than CT with LI-RADS TRA (30.8%, p < 0.001) or MRI with mRECIST (38.5%, p < 0.001). CONCLUSIONS: MRI with mRECIST was the optimal radiologic method to determine MC for the prediction of post-LT recurrence in HCC patients with prior LRT. KEY POINTS: • MRI with modified RECIST (mRECIST) is the optimal preoperative method to determine Milan criteria for the prediction of post-transplant HCC recurrence in patients with prior locoregional treatment. • With mRECIST, MRI was better than CT for the prediction of post-transplant recurrence.

The Role of Macrophage Populations in Skeletal Muscle Insulin Sensitivity: Current Understanding and Implications.

Insulin resistance is a crucial factor in the development of type 2 diabetes mellitus (T2DM) and other metabolic disorders. Skeletal muscle, the body's largest insulin-responsive tissue, plays a significant role in the pathogenesis of T2DM due to defects in insulin signaling. Recently, there has been growing evidence that macrophages, immune cells essential for tissue homeostasis and injury response, also contribute to the development of skeletal muscle insulin resistance. This review aims to summarize the current understanding of the role of macrophages in skeletal muscle insulin resistance. Firstly, it provides an overview of the different macrophage populations present in skeletal muscle and their specific functions in the development of insulin resistance. Secondly, it examines the underlying mechanisms by which macrophages promote or alleviate insulin resistance in skeletal muscle, including inflammation, oxidative stress, and altered metabolism. Lastly, the review discusses potential therapeutic strategies targeting macrophages to improve skeletal muscle insulin sensitivity and metabolic health.

CT/MRI and CEUS LI-RADS Major Features Association with Hepatocellular Carcinoma: Individual Patient Data Meta-Analysis.

Background The Liver Imaging Reporting and Data System (LI-RADS) assigns a risk category for hepatocellular carcinoma (HCC) to imaging observations. Establishing the contributions of major features can inform the diagnostic algorithm. Purpose To perform a systematic review and individual patient data meta-analysis to establish the probability of HCC for each LI-RADS major feature using CT/MRI and contrast-enhanced US (CEUS) LI-RADS in patients at high risk for HCC. Materials and Methods Multiple databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus) were searched for studies from January 2014 to September 2019 that evaluated the accuracy of CT, MRI, and CEUS for HCC detection using LI-RADS (CT/MRI LI-RADS, versions 2014, 2017, and 2018; CEUS LI-RADS, versions 2016 and 2017). Data were centralized. Clustering was addressed at the study and patient levels using mixed models. Adjusted odds ratios (ORs) with 95% CIs were determined for each major feature using multivariable stepwise logistic regression. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) (PROSPERO protocol: CRD42020164486). Results A total of 32 studies were included, with 1170 CT observations, 3341 MRI observations, and 853 CEUS observations. At multivariable analysis of CT/MRI LI-RADS, all major features were associated with HCC, except threshold growth (OR, 1.6; 95% CI: 0.7, 3.6; P = .07). Nonperipheral washout (OR, 13.2; 95% CI: 9.0, 19.2; P = .01) and nonrim arterial phase hyperenhancement (APHE) (OR, 10.3; 95% CI: 6.7, 15.6; P = .01) had stronger associations with HCC than enhancing capsule (OR, 2.4; 95% CI: 1.7, 3.5; P = .03). On CEUS images, APHE (OR, 7.3; 95% CI: 4.6, 11.5; P = .01), late and mild washout (OR, 4.1; 95% CI: 2.6, 6.6; P = .01), and size of at least 20 mm (OR, 1.6; 95% CI: 1.04, 2.5; P = .04) were associated with HCC. Twenty-five studies (78%) had high risk of bias due to reporting ambiguity or study design flaws. Conclusion Most Liver Imaging Reporting and Data System major features had different independent associations with hepatocellular carcinoma; for CT/MRI, arterial phase hyperenhancement and washout had the strongest associations, whereas threshold growth had no association. © RSNA, 2021 Online supplemental material is available for this article.

Incorporation of Ancillary MRI Features Into the LI-RADS Treatment Response Algorithm: Impact on Diagnostic Performance After Locoregional Treatment of Hepatocellular Carcinoma.

BACKGROUND. The LI-RADS treatment response algorithm may lack sufficient sensitivity for viable tumor after locoregional treatment (LRT) for hepatocellular carcinoma (HCC). OBJECTIVE. The purpose of our study was to evaluate the impact of incorporation of ancillary MRI features on the diagnostic performance of the LI-RADS treatment response algorithm after LRT for HCC. METHODS. This retrospective study included 141 patients (114 men, 27 women; median age, 56 years) who underwent gadoxetic acid-enhanced MRI after LRT for HCC between October 2005 and January 2020 and subsequent liver surgery. Two readers assessed lesions for LI-RADS features of viability for ancillary MRI features (transitional phase [TP] hypointensity, hepatobiliary phase [HBP] hypointensity, DWI hyperintensity or low ADC, and mild-to-moderate T2 hyperintensity). Interobserver agreement was assessed before reaching consensus. Significant ancillary features were identified using random forest analysis. The impact of incorporation of significant ancillary features on diagnostic performance for incomplete pathologic necrosis (IPN; pathologically viable tumor > 0 mm) was assessed using McNemar tests. RESULTS. Complete pathologic necrosis (CPN) was observed in 88 of 181 (48.6%) lesions. Interreader agreement was almost perfect for LI-RADS features of viability (κ = 0.92-0.97) and was substantial to almost perfect for ancillary features (κ = 0.73-0.94). Random forest analysis identified TP hypointensity (present in 8.0%, 25.0%, and 75.3% of lesions with CPN, viable tumor < 10 mm, and viable tumor ≥ 10 mm, respectively) and HBP hypointensity (9.2%, 25.0%, and 74.0%, respectively) as significant ancillary features. For detecting IPN, LR-TR (treatment response) Viable or LR-TR Equivocal had higher sensitivity than LR-TR Viable (71.0% vs 57.0%, respectively; p = .001) but had lower specificity (86.4% vs 94.3%, p = .02). However, LR-TR Viable or LR-TR Equivocal and TP hypointensity showed higher sensitivity than LR-TR Viable (64.5% vs 57.0%, p = .02) without a significantly different specificity (90.9% vs 94.3%, p = .25). LR-TR Viable or LR-TR Equivocal and HBP hypointensity also showed higher sensitivity than LR-TR Viable (65.6% vs 57.0%, p = .01) without a significantly different specificity (90.8% vs 94.3%, p = .25). CONCLUSION. TP hypointensity and HBP hypointensity increase the sensitivity of LI-RADS treatment response algorithm for viable tumor without lowering specificity. CLINICAL IMPACT. The two identified ancillary features may improve tumor viability assessment and planning of additional therapies after LRT for HCC.

Comparison of Sensitivity Encoding (SENSE) and Compressed Sensing-SENSE for Contrast-Enhanced T1-Weighted Imaging in Patients With Crohn Disease Undergoing MR Enterography.

BACKGROUND. Long acquisition times for breath-hold contrast-enhanced (CE) T1-weighted imaging in MR enterography (MRE) protocols result in reduced image quality. OBJECTIVE. The purpose of this study was to compare CE T1-weighted imaging performed using sensitivity encoding (SENSE) and compressed sensing-SENSE (CS-SENSE) in terms of image quality and diagnostic performance for active inflammation in Crohn disease (CD). METHODS. This retrospective study included 41 patients (31 men, 10 women; mean age, 34 ± 12 [SD] years) who underwent MRE for known or suspected CD between June 2020 and September 2020. MRE was performed in one of two scanning rooms depending on scheduling availability. Per institutional protocol, in one room, the enteric phase was acquired using SENSE (acceleration factor, 3) and the portal phase was acquired using CS-SENSE (acceleration factor, 5); this order was reversed in the other room. Two radiologists independently assessed sequences for subjective image quality measures at the patient level and for active inflammation at the bowel-segment level. Mean image quality scores between readers were computed. Diagnostic performance for active inflammation was compared between SENSE and CS-SENSE using generalized estimating equations; a separate experienced radiologist reviewed the full MRE protocol to establish the reference standard. RESULTS. The mean acquisition time of CE T1-weighted imaging was 17.2 ± 1.1 seconds for SENSE versus 11.5 ± 0.8 seconds for CS-SENSE (p < .001). CS-SENSE scored significantly better than SENSE in overall image quality (4.2 ± 0.7 vs 3.7 ± 1.1; p = .02), motion artifacts (4.0 ± 0.8 vs 3.6 ± 1.2; p = .006), and aliasing artifacts (4.8 ± 0.4 vs 4.2 ± 0.6; p < .001). CS-SENSE scored significantly worse than SENSE in synthetic appearance (4.6 ± 0.5 vs 4.8 ± 0.4; p = .003). Contrast, sharpness, and blurring were not different between sequences (p > .05). For reader 1, CS-SENSE, compared with SENSE, showed a sensitivity of 86% versus 81% (p = .09), specificity of 88% versus 83% (p = .08), and accuracy of 87% versus 82% (p = .56). For reader 2, CS-SENSE, compared with SENSE, showed a sensitivity of 92% versus 79% (p = .006), specificity of 90% versus 98% (p = .16), and accuracy of 91% versus 86% (p = .002). CONCLUSION. Use of CS-SENSE for CE T1-weighted imaging in MRE protocols results in reduced scan times with reduced artifact and improved image quality. CLINICAL IMPACT. The benefits of CS-SENSE in MRE protocols may improve the diagnostic performance for active inflammation in CD.

Potential Beneficial Effects of Sargassum spp. in Skin Aging.

Seaweeds are receiving much attention as a rich source of bioactive compounds with cosmeceutical potential. Recent studies have revealed that Sargassum spp., a genus of brown algae in the family Sargassaceae, has multiple functions in preventing and improving skin aging. Sargassum spp. contains many bioactive compounds, such as fucoidan, fucoxanthin, terpenoids, flavonoids, and meroterpenoids. These Sargassum spp. extracts and derivative compounds have excellent potential for skincare, as they exhibit skin health-promoting properties, including antioxidants, anti-inflammation, whitening, skin barrier repair, and moisturizing. Therefore, searching for bioactive compounds in marine resources such as Sargassum spp. could be an attractive approach to preventing and improving skin aging. The current review focused on the various biological abilities of Sargassum extracts or derived compounds for anti-skin aging.

Gadoxetic acid-enhanced MRI of macrotrabecular-massive hepatocellular carcinoma and its prognostic implications.

BACKGROUND & AIMS: Despite the clinical and genetic significance of macrotrabecular-massive hepatocellular carcinoma (MTM-HCC), its characteristics on imaging have not been described. This study aimed to characterise MTM-HCC on gadoxetic acid-enhanced MRI and to evaluate the diagnostic accuracy and prognostic value of these imaging characteristics. METHODS: We enrolled 3 independent cohorts from 2 tertiary care centres. The 3 cohorts consisted of a total of 476 patients who underwent gadoxetic acid-enhanced MRI and surgical resection for treatment-naïve single HCCs. Independent review of histopathology and MRI by 2 reviewers was performed for each cohort, and inter-reader agreement was evaluated. Based on the result of MRI review in the training cohort (cohort 1), we developed 2 diagnostic criteria for MTM-HCC and evaluated their prognostic significance. The diagnostic performance and prognostic significance were validated in 2 validation cohorts (cohorts 2 and 3). RESULTS: We developed 2 diagnostic MRI criteria (MRIC) for MTM-HCC: MRIC-1, ≥20% arterial phase hypovascular component; MRIC-2, ≥50% hypovascular component and 2 or more ancillary findings (intratumoural artery, arterial phase peritumoural enhancement, and non-smooth tumour margin). MRIC-1 showed high sensitivity and negative predictive value (88% and 95% in the training cohort, and 88% and 97% in the pooled validation cohorts, respectively), whereas MRIC-2 demonstrated moderate sensitivity and high specificity (47% and 94% in the training cohort, and 46% and 96% in the pooled validation cohorts, respectively). MRIC-2 was an independent poor prognostic factor for overall survival in both training and pooled validation cohorts. CONCLUSIONS: Using gadoxetic acid-enhanced MRI findings, including an arterial phase hypovascular component, we could stratify the probability of MTM-HCC and non-invasively obtain prognostic information. LAY SUMMARY: Macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) is a histopathologic subtype of HCC characterised by aggressive biological behaviour and poor prognosis. We developed imaging criteria based on liver MRI that could be used for the non-invasive diagnosis of MTM-HCC. HCCs showing imaging findings of MTM-HCC were associated with poor outcomes after hepatic resection.

Characteristics and Early Recurrence of Hepatocellular Carcinomas Categorized as LR-M: Comparison with Those Categorized as LR-4 or 5.

BACKGROUND: According to the Liver Imaging Reporting and Data System (LI-RADS), the LI-RADS category M (LR-M), which are probably or definitely malignant but are not specific for hepatocellular carcinomas (HCCs), does not exclude HCCs. A gap in knowledge remains, including their characteristics and recurrence of HCCs categorized as LR-M. PURPOSE: To compare the characteristics of HCCs categorized as LR-M with HCCs categorized as LR-4 or LR-5 (LR-4/5) using the LI-RADS version 2018 and evaluate the relationship of these categories with the risk of early recurrence after curative resections of single HCCs. STUDY TYPE: Retrospective. SUBJECTS: Two hundred and eighty-one patients (mean age, 57 years; 191 men and 90 women) who underwent curative resections for single HCCs and preoperative contrast-enhanced MRI between 2015 and 2017. FIELD STRENGTH/SEQUENCE: 3T Dual gradient-echo T1 WI with in- and opposed-phase, turbo spin-echo T2 WI, diffusion-weighted echo-planar images, and three-dimensional gradient-echo T1 WI before and after administration of contrast agent. ASSESSMENT: MRI features according to the LI-RADS version 2018 were evaluated and LI-RADS category were assigned for each observation. Clinical, imaging, and histopathological features were compared based on LI-RADS categorization. Early recurrence rates (<2 years) and associated factors were also evaluated. STATISTICAL TESTS: Fisher's exact test, two-sample t test after satisfying assumption of normality through Shapiro-Wilk test, Fleiss κ coefficient, Cox proportional hazards regression analysis, Kaplan-Meier method, and log-rank test. RESULTS: Forty-one HCCs (14.6%) were categorized as LR-M and 240 HCCs (85.4%) were categorized as LR-4/5. LR-M HCCs showed poorer differentiation than LR-4/5 HCCs. In the multivariate analysis, the LR-M category was an independent predictor for early recurrence (hazard ratio, 1.904; 95% confidence interval, 1.024-3.542; P < 0.05). Early recurrence rates were significantly higher in patients with LR-M HCCs than in patients with LR-4/5 HCCs (32.0% vs. 18.4%, respectively, P < 0 05). DATA CONCLUSION: Compared to LR-4/5 HCCs, LR-M HCCs were associated with poorer tumor differentiation and higher early recurrence rates after curative resections of single HCCs. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 2.

Prognostic factors of gadoxetic acid-enhanced MRI for postsurgical outcomes in multicentric hepatocellular carcinoma.

OBJECTIVES: The primary aim of this study was to determine the clinical and histopathological prognostic factors for patients who underwent surgical resection of multiple hepatocellular carcinomas (HCCs) of multicentric occurrence. The secondary aim of this study was to evaluate whether specific imaging-related factors, including arterial phase hyperenhancement (APHE) and the LI-RADS category of each lesion on gadoxetic acid-enhanced MRI, would provide additional prognostic information about multicentric HCCs. METHODS: In this retrospective study, 54 patients with 120 multicentric HCCs were diagnosed by surgical resection at a single tertiary hospital between 2009 and 2014. Two independent readers evaluated patients' preoperative gadoxetic acid-enhanced MR images and recorded APHE and LI-RADS category for each HCC, with discrepancies resolved through consensus sessions if necessary. Potential clinicopathologic and imaging parameters for predicting disease-free survival (DFS) and overall survival (OS) were analyzed using Cox regression analysis. RESULTS: Presence of microvascular invasion (MVI) (p = 0.003) and of three or more HCCs (p = 0.013) were both independent predictors of a shorter DFS. Patients with concurrent MVI and three or more HCCs had the shortest DFS. MVI was the only statistically significant parameter (p = 0.023) predicting OS. The number of HCCs with APHE or LR-5/M category was not associated with survival. CONCLUSIONS: Presence of MVI and of three or more HCCs were associated with poorer outcomes after surgical resection of multicentric HCCs. Imaging parameters on gadoxetic acid-enhanced MRI such as APHE or LI-RADS category were not associated with postsurgical outcomes. KEY POINTS: • Patients with three or more hepatocellular carcinomas showed worse disease-free survival than those with two hepatocellular carcinomas after surgical resection. • Microvascular invasion was the only significant factor to affect both the disease-free and overall survivals of patients after surgical resection of multicentric hepatocellular carcinomas. • Preoperative MRI findings related to multicentric hepatocellular carcinomas such as arterial phase hyperenhancement and LI-RADS category of lesions did not provide significant prognostic information.

Application of Liver Imaging Reporting and Data System version 2018 ancillary features to upgrade from LR-4 to LR-5 on gadoxetic acid-enhanced MRI.

OBJECTIVES: The current LR-5 criteria of Liver Imaging Reporting and Data System (LI-RADS) determined by only major features provide high specificity, but unsatisfactorily low sensitivity for the noninvasive diagnosis of hepatocellular carcinoma (HCC). This study aimed to identify significant ancillary features (AFs) in LI-RADS version 2018 and develop the upgraded LR-5 criteria to improve diagnostic performance on gadoxetic acid-enhanced magnetic resonance imaging (MRI). METHODS: This retrospective study included 280 patients (366 observations including 281 HCCs) at high-risk for HCC who underwent gadoxetic acid-enhanced MRI between 2015 and 2017. Two readers evaluated major features and AFs for each observation and assigned a LI-RADS category. Independently significant AFs were identified through logistic regression analysis. Upgraded LR-5 criteria were developed by combining independently significant AFs with LR-4 assigned by major features alone. Sensitivities and specificities of the diagnostic criteria were compared using McNemar's test. RESULTS: Two of the AFs favoring malignancy in general (mild-moderate T2 hyperintensity and hepatobiliary phase hypointensity) and two of the AFs favoring HCC in particular (nonenhancing "capsule" and mosaic architecture) were independently significant features for diagnosing HCC. By using the upgraded LR-5 criteria (LR-4 by major features alone + each aforementioned AF), sensitivities were significantly increased (69.4-76.9%) compared with the standard LR-5 (66.2%; all, p ≤ 0.004), whereas specificities (95.3-96.5%) were not significantly different (96.5%; all, p > 0.999). CONCLUSIONS: Independently significant AFs may be used to upgrade from LR-4 to LR-5 to improve sensitivity without impairing specificity on gadoxetic acid-enhanced MRI. KEY POINTS: • Independently significant AFs for HCC on gadoxetic acid-enhanced MRI were mild-moderate T2 hyperintensity, hepatobiliary phase hypointensity, nonenhancing "capsule," and mosaic architecture. • When LR-4 criteria by major features alone in combination with significant AFs were upgraded to LR-5, sensitivities were higher than the standard LR-5, without impairing specificity. • Independently significant ancillary features in Liver Imaging Reporting and Data System version 2018 may be used to upgrade from LR-4 to LR-5 to improve sensitivity without impairing specificity on gadoxetic acid-enhanced MRI.