1.Combination of CT/MRI LI-RADS With Second-Line Contrast-Enhanced Ultrasound Using Sulfur Hexafluoride or Perfluorobutane for Diagnosing Hepatocellular Carcinoma in High-Risk Patients
Yu LI ; Sheng LI ; Qing LI ; Kai LI ; Jing HAN ; Siyue MAO ; Xiaohong XU ; Zhongzhen SU ; Yanling ZUO ; Shousong XIE ; Hong WEN ; Xuebin ZOU ; Jingxian SHEN ; Lingling LI ; Jianhua ZHOU
Korean Journal of Radiology 2025;26(4):346-359
Objective:
The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB).
Materials and Methods:
This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB.
Results:
In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%).
Conclusion
The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.
2.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
3.Feasibility and safety study of ultra-hypofractionated neoadjuvant radiotherapy to margins-at-risk in retroperitoneal sarcoma
Ru-Xin WONG ; Valerie Shi Wen YANG ; Clarame Shulyn CHIA ; Wen Shen LOOI ; Wen Long NEI ; Chin-Ann Johnny ONG
Radiation Oncology Journal 2025;43(1):6-12
Purpose:
Retroperitoneal sarcomas (RPS) are rare tumors that present unique challenges, often due to late presentation, and the proximity of critical organs makes complete surgical resection challenging. This study aimed to assess the feasibility of neoadjuvant short-course radiotherapy (SCRT) targeting margins-at-risk and to assess its potential impact on outcomes.
Materials and Methods:
This is a single-center, prospective, non-randomized feasibility study. SCRT was administered via image-guided volumetric modulated arc therapy, consisting of 5 fractions of daily radiotherapy followed by immediate surgery. As a starting dose, patients were prescribed 25 Gy in 5 fractions. For the escalation stage, patients were prescribed 30 Gy in 5 fractions. Only the presumed threatened surgical margins were delineated for large tumors.
Results:
Patients with either primary or recurrent RPS were recruited. Eight patients underwent SCRT but one patient did not have a resection as planned. Seven patients underwent surgical resection, of whom one passed away 3 months postoperative from a cardiac event. After a median follow-up of 20.5 months for the six postoperative survivors, there were no overt long-term toxicities and one patient relapsed out-of-radiotherapy-field.
Conclusion
SCRT to RPS with a margin boost followed by immediate surgery is worth investigating. A starting dose of 30 Gy in 5 fractions is recommended for further studies. Longer-term follow-up is necessary.
4.Bone marrow mesenchymal stem cells improve bone cancer pain by inhibiting p38MAPK phosphorylation and microglia activation
Houming KAN ; Jinzhao HUANG ; Xiaodie GUI ; Wendi TIAN ; Lijun FAN ; Xuetai CHEN ; Xiaotong DING ; Liping CHEN ; Wen SHEN
The Korean Journal of Pain 2025;38(2):116-127
Background:
Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment.
Methods:
We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs.
Results:
Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4.
Conclusions
Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.
5.Research on the effectiveness of health information dissemination via the “Shanghai CDC” WeChat public account
Ying GUO ; Xiaoxuan WANG ; Wen XIA ; Xiaoyan HUANG ; Xuanmeng HU ; Qi SHEN ; Chen DONG
Shanghai Journal of Preventive Medicine 2025;37(2):179-183
ObjectiveTo explore the effectiveness of health information dissemination and its influencing factors using the "Shanghai CDC" WeChat public account as a case study, providing references for public health institutions to optimize the use of official new media platforms for effective publicity. MethodsA total of 1 030 headline articles published on the "Shanghai CDC" WeChat public account between 2016 and 2019 were analyzed using content analysis and non-parametric tests to examine the impact of factors such as titles and content categories. ResultsFrom 2016 to 2019, the number of WeChat public account followers increased by 280 000, with the articles accumulating over 8.8 million views. The median (P25, P75) open rate of articles was 5.90% (3.69%, 10.31%), and the median (P25, P75) sharing and forwarding rate was 6.60% (4.25%, 9.17%). Factors such as the use of first- and second-person pronouns, degree adverbs, negative adverbs, explicit viewpoints, and title length all significantly affected the open rate of articles, with OR (95%CI) values of 0.175 (0.041‒0.756), 32.606 (2.350‒452.432), 4.079 (1.093‒15.230), 0.106 (0.028‒0.409), and 1.184 (1.063‒1.319),respectively (all P<0.05). In terms of content, statistical significant differences in dissemination effectiveness were observed across article categories and themes (P<0.05). In terms of article categories, articles related to news hotspots and service information had higher open rates of 9.58% and 14.00%, respectively. These two types of articles also obtained higher sharing and forwarding rates of 7.65% and 9.16%, respectively. In terms of article topics, compared with healthy life and health products, among the top four topics in terms of publication volume, the open rates of articles about infectious diseases and disease-causing biology and immunization programs were higher, accounting for 7.88% and 6.88%, respectively, with no significant difference in sharing and forwarding rates. ConclusionThe "Shanghai CDC" WeChat public account demonstrated good dissemination effectiveness. Enhancing article titles by increasing informational content and degree adverbs (e.g., "highly," "most," and "extremely") and negative adverbs (e.g., "no") can improve dissemination reach. Public health WeChat accounts should incorporate news hotspots or service information in their articles. While maintaining their strengths in disseminating knowledge on infectious diseases and immunization programs, they should also enhance public education in other professional fields within their scope of responsibility to improve the overall dissemination impact of health information.
6.Mechanisms of Zhuyuwan in Treating both Intrahepatic Cholestasis and Ulcerative Colitis Based on Homotherapy for Heteropathy
Jun HAN ; Yueqiang WEN ; Zongying XU ; Dan LUO ; Li ZHOU ; Xueyi LI ; Yufan DAI ; Lele YANG ; Tao SHEN ; Han YU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):46-53
ObjectiveThe theory of homotherapy for heteropathy is one of the classical rules in traditional Chinese medicine. Taking this theory as a breakthrough point, this study employed gas chromatography-mass spectrometry (GC-MS) to elucidate the mechanism underlying the therapeutic effects of Zhuyuwan on both intrahepatic cholestasis (IC) and ulcerative colitis (UC) from the viewpoint of serum metabolic homeostasis. MethodsThe rat models of α-naphthylisothiocyanate (ANIT)-induced cholestasis and 2,4,6-trinitro-benzenesulfonic acid (TNBS)-induced UC were treated with low (0.6 g·kg-1) and high (1.2 g·kg-1) doses of Zhuyuwan by gavage. In the experiment regarding IC, 24 Sprague-Dawley (SD) rats were randomly assigned into four groups: normal, ANIT model, low-dose Zhuyuwan, and high-dose Zhuyuwan. In the experiment regarding UC, 24 SD rats were randomly allocated into four groups: normal, TNBS model, low-dose Zhuyuwan, and high-dose Zhuyuwan. Firstly, the two disease models and the intervention effects of Zhuyuwan on the two diseases were evaluated based on serum levels of biochemical indicators [alanine aminotransferase (ALT), aspartate transaminase (AST), γ-glutamyltranspeptidase (γ-GT), and total bile acid (TBA)], colon damage score, colon weight index, disease activity index, and histopathological changes in rats. Secondly, the rat serum samples were analyzed by gas chromatography-mass spectrometry (GC-MS) to screen the common core pathways of the two disease models, and the expression of core genes in the pathways was determined by Real-time PCR, on the basis of which the biological mechanism of the treatment of the two disease models by Zhuyuwan was ultimately elucidated. ResultsThe results of the experiment regarding IC showed that the ANIT model group had higher ALT, AST, γ-GT, and TBA levels than the normal group (P<0.01). Compared with the ANIT model group, the low-dose Zhuyuwan group showed declined ALT and TBA levels (P<0.01) and the high-dose Zhuyuwan group showed lowered ALT, TBA, AST, and γ-GT levels (P<0.01). The results of the experiment regarding UC showed that compared with the normal group, the TNBS model group presented increases in the colonic damage score, colon weight index, and disease activity index (P<0.01). Compared with the TNBS model group, the low-dose Zhuyuwan group showcased declines in colon weight index (P<0.01) and disease activity index (P<0.05), and the high-dose Zhuyuwan group showed reductions in the colon damage score, colon weight index, and disease activity index (P<0.01). GC-MS metabolomics analysis combined with qRT-PCR demonstrated that Zhuyuwan had a similar inverse regulatory effect on arginine metabolism disruption in the above two disease models. ConclusionZhuyuwan exhibited definite therapeutic effects on both IC and UC, and the regulation of arginine biosynthesis pathway is the core mechanism for the treatment of both diseases by Zhuyuwan.
7.Mechanism of Ethoxysanguinarine in Regulating IRE1/RIDD Signaling Pathway to Inhibit Endoplasmic Reticulum Stress and Alleviate Cardiomyocyte Apoptosis
Zucheng SHANG ; Hongzheng LI ; Mengfan LI ; Wen SUN ; Guosheng LIN ; Aling SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):141-148
ObjectiveTo investigate the effects of ethoxysanguinarine (ETH) on angiotensin Ⅱ (Ang Ⅱ)-mediated cardiomyocyte apoptosis and its regulatory effects of inositol-requiring enzyme 1 (IRE1)/regulated IRE1-dependent decay (RIDD) signaling pathway and endoplasmic reticulum stress. MethodsWestern blot was used to detect the establishment of the H9c2 model via Ang Ⅱ stimulation, which was identified as a cardiomyocyte apoptosis model. Subsequently, the inhibitory effect of ETH on cell proliferation was assessed using the cell counting Kit-8 (CCK-8) to determine the optimal effective dose of ETH. H9c2 cardiomyocytes were divided into a blank group, a model group (Ang Ⅱ, 1 mmol·L-1), and low-, medium-, and high-dose ETH groups (1.25, 2.5, and 5 mmol·L-1). Morphological changes in cardiomyocytes induced by Ang Ⅱ were detected using phalloidin staining. Cardiomyocyte apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick and labeling (TUNEL) staining. The apoptosis cycle was detected by Annexin V/PI flow cytometry. Western blot was used to detect the expression levels of apoptosis-related proteins, endoplasmic reticulum stress, and IRE1/RIDD pathway-related proteins. ResultsWestern blot results showed that 1 mmol/mL Ang Ⅱ stimulation significantly increased the protein expression levels of Bip, p-IRE1, and Bid in H9c2 cells (P<0.05, P<0.01), indicating the induction of endoplasmic reticulum stress, activation of the IRE1/RIDD signaling pathway, and initiation of the apoptosis process. Compared with the blank group, the model group showed a significant increase in the surface area of H9c2 cells and the apoptosis rate of cardiomyocytes, as well as in both early and late apoptosis rates (P<0.01). The expression levels of Bid, Bax, cleaved-Caspase-3, and cleaved-Caspase-8 proteins were significantly increased, while the expression level of Bcl-2 protein was significantly decreased (P<0.01). The expression levels of Bip, p-IRE1, and p-RIDD proteins were significantly increased (P<0.05, P<0.01). Compared with those in the model group, the surface area of cardiomyocytes and the apoptosis rate of cardiomyocytes in all ETH groups were significantly decreased after drug intervention. Both early and late apoptosis rates were significantly decreased. The expression level of cleaved-Caspase-8 was significantly decreased in the low-dose ETH group (P<0.05). The expression levels of Bid, Bax, and cleaved-Caspase-8 were significantly decreased in the medium-dose ETH group (P<0.05, P<0.01). The high-dose ETH group significantly reduced the expression levels of Bid, Bax, cleaved-Caspase-3, and cleaved-Caspase-8 (P<0.05, P<0.01) and significantly increased the expression level of Bcl-2 (P<0.05). The level of p-IRE1 protein in the medium-dose ETH group was significantly decreased (P<0.01). The expression levels of Bip, p-IRE1, and p-RIDD proteins in the high-dose ETH group were significantly decreased (P<0.05, P<0.01). ConclusionETH can alleviate Ang Ⅱ-mediated cardiomyocyte apoptosis by inhibiting the IRE1/RIDD signaling pathway and further alleviate the cardiac injury caused by hypertension.
8.Mechanisms of Zhuyuwan in Treating both Intrahepatic Cholestasis and Ulcerative Colitis Based on Homotherapy for Heteropathy
Jun HAN ; Yueqiang WEN ; Zongying XU ; Dan LUO ; Li ZHOU ; Xueyi LI ; Yufan DAI ; Lele YANG ; Tao SHEN ; Han YU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):46-53
ObjectiveThe theory of homotherapy for heteropathy is one of the classical rules in traditional Chinese medicine. Taking this theory as a breakthrough point, this study employed gas chromatography-mass spectrometry (GC-MS) to elucidate the mechanism underlying the therapeutic effects of Zhuyuwan on both intrahepatic cholestasis (IC) and ulcerative colitis (UC) from the viewpoint of serum metabolic homeostasis. MethodsThe rat models of α-naphthylisothiocyanate (ANIT)-induced cholestasis and 2,4,6-trinitro-benzenesulfonic acid (TNBS)-induced UC were treated with low (0.6 g·kg-1) and high (1.2 g·kg-1) doses of Zhuyuwan by gavage. In the experiment regarding IC, 24 Sprague-Dawley (SD) rats were randomly assigned into four groups: normal, ANIT model, low-dose Zhuyuwan, and high-dose Zhuyuwan. In the experiment regarding UC, 24 SD rats were randomly allocated into four groups: normal, TNBS model, low-dose Zhuyuwan, and high-dose Zhuyuwan. Firstly, the two disease models and the intervention effects of Zhuyuwan on the two diseases were evaluated based on serum levels of biochemical indicators [alanine aminotransferase (ALT), aspartate transaminase (AST), γ-glutamyltranspeptidase (γ-GT), and total bile acid (TBA)], colon damage score, colon weight index, disease activity index, and histopathological changes in rats. Secondly, the rat serum samples were analyzed by gas chromatography-mass spectrometry (GC-MS) to screen the common core pathways of the two disease models, and the expression of core genes in the pathways was determined by Real-time PCR, on the basis of which the biological mechanism of the treatment of the two disease models by Zhuyuwan was ultimately elucidated. ResultsThe results of the experiment regarding IC showed that the ANIT model group had higher ALT, AST, γ-GT, and TBA levels than the normal group (P<0.01). Compared with the ANIT model group, the low-dose Zhuyuwan group showed declined ALT and TBA levels (P<0.01) and the high-dose Zhuyuwan group showed lowered ALT, TBA, AST, and γ-GT levels (P<0.01). The results of the experiment regarding UC showed that compared with the normal group, the TNBS model group presented increases in the colonic damage score, colon weight index, and disease activity index (P<0.01). Compared with the TNBS model group, the low-dose Zhuyuwan group showcased declines in colon weight index (P<0.01) and disease activity index (P<0.05), and the high-dose Zhuyuwan group showed reductions in the colon damage score, colon weight index, and disease activity index (P<0.01). GC-MS metabolomics analysis combined with qRT-PCR demonstrated that Zhuyuwan had a similar inverse regulatory effect on arginine metabolism disruption in the above two disease models. ConclusionZhuyuwan exhibited definite therapeutic effects on both IC and UC, and the regulation of arginine biosynthesis pathway is the core mechanism for the treatment of both diseases by Zhuyuwan.
9.Mechanism of Ethoxysanguinarine in Regulating IRE1/RIDD Signaling Pathway to Inhibit Endoplasmic Reticulum Stress and Alleviate Cardiomyocyte Apoptosis
Zucheng SHANG ; Hongzheng LI ; Mengfan LI ; Wen SUN ; Guosheng LIN ; Aling SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):141-148
ObjectiveTo investigate the effects of ethoxysanguinarine (ETH) on angiotensin Ⅱ (Ang Ⅱ)-mediated cardiomyocyte apoptosis and its regulatory effects of inositol-requiring enzyme 1 (IRE1)/regulated IRE1-dependent decay (RIDD) signaling pathway and endoplasmic reticulum stress. MethodsWestern blot was used to detect the establishment of the H9c2 model via Ang Ⅱ stimulation, which was identified as a cardiomyocyte apoptosis model. Subsequently, the inhibitory effect of ETH on cell proliferation was assessed using the cell counting Kit-8 (CCK-8) to determine the optimal effective dose of ETH. H9c2 cardiomyocytes were divided into a blank group, a model group (Ang Ⅱ, 1 mmol·L-1), and low-, medium-, and high-dose ETH groups (1.25, 2.5, and 5 mmol·L-1). Morphological changes in cardiomyocytes induced by Ang Ⅱ were detected using phalloidin staining. Cardiomyocyte apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick and labeling (TUNEL) staining. The apoptosis cycle was detected by Annexin V/PI flow cytometry. Western blot was used to detect the expression levels of apoptosis-related proteins, endoplasmic reticulum stress, and IRE1/RIDD pathway-related proteins. ResultsWestern blot results showed that 1 mmol/mL Ang Ⅱ stimulation significantly increased the protein expression levels of Bip, p-IRE1, and Bid in H9c2 cells (P<0.05, P<0.01), indicating the induction of endoplasmic reticulum stress, activation of the IRE1/RIDD signaling pathway, and initiation of the apoptosis process. Compared with the blank group, the model group showed a significant increase in the surface area of H9c2 cells and the apoptosis rate of cardiomyocytes, as well as in both early and late apoptosis rates (P<0.01). The expression levels of Bid, Bax, cleaved-Caspase-3, and cleaved-Caspase-8 proteins were significantly increased, while the expression level of Bcl-2 protein was significantly decreased (P<0.01). The expression levels of Bip, p-IRE1, and p-RIDD proteins were significantly increased (P<0.05, P<0.01). Compared with those in the model group, the surface area of cardiomyocytes and the apoptosis rate of cardiomyocytes in all ETH groups were significantly decreased after drug intervention. Both early and late apoptosis rates were significantly decreased. The expression level of cleaved-Caspase-8 was significantly decreased in the low-dose ETH group (P<0.05). The expression levels of Bid, Bax, and cleaved-Caspase-8 were significantly decreased in the medium-dose ETH group (P<0.05, P<0.01). The high-dose ETH group significantly reduced the expression levels of Bid, Bax, cleaved-Caspase-3, and cleaved-Caspase-8 (P<0.05, P<0.01) and significantly increased the expression level of Bcl-2 (P<0.05). The level of p-IRE1 protein in the medium-dose ETH group was significantly decreased (P<0.01). The expression levels of Bip, p-IRE1, and p-RIDD proteins in the high-dose ETH group were significantly decreased (P<0.05, P<0.01). ConclusionETH can alleviate Ang Ⅱ-mediated cardiomyocyte apoptosis by inhibiting the IRE1/RIDD signaling pathway and further alleviate the cardiac injury caused by hypertension.
10.Combination of CT/MRI LI-RADS With Second-Line Contrast-Enhanced Ultrasound Using Sulfur Hexafluoride or Perfluorobutane for Diagnosing Hepatocellular Carcinoma in High-Risk Patients
Yu LI ; Sheng LI ; Qing LI ; Kai LI ; Jing HAN ; Siyue MAO ; Xiaohong XU ; Zhongzhen SU ; Yanling ZUO ; Shousong XIE ; Hong WEN ; Xuebin ZOU ; Jingxian SHEN ; Lingling LI ; Jianhua ZHOU
Korean Journal of Radiology 2025;26(4):346-359
Objective:
The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB).
Materials and Methods:
This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB.
Results:
In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%).
Conclusion
The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

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