Purpose: To identify US findings suggestive of malignancy in thyroid nodules with follicular lesions of undetermined significance (FLUS) or follicular neoplasm (FN) on fine-needle aspiration cytology (FNAC) and evaluate the diagnostic performance. Materials and Methods: Seventy FLUS (n = 57) or FN (n = 13) nodules on FNAC that underwent surgical excision between February 2018 and November 2020 were selected. US findings were retrospectively reviewed. Orientation, margin, echogenicity, calcification, additional findings of the rim, echogenicity, heterogeneity of the solid portion, and the ratio of anterior posterior diameter to lateral diameter (criteria) were assessed. The diagnostic performances of US findings, criteria, and the Korean Society of Thyroid Radiology Thyroid Imaging Reporting and Data System (K-TIRADS) were evaluated using logistic regression analysis. Results: Microcalcification, homogeneous solid echotexture, and thickened rims were suggestive of malignancy. Our criteria showed a highest area under the ROC curve (AUC) value of 0.771, sensitivity of 97.14%, accuracy of 77.14%, positive predictive value of 93.33%, negative predictive value of 95.24%, and specificity of 97.14%. The criteria showed a significantly higher AUC value than K-TIRADS. Conclusion US findings of homogenous solid portions, thick rims, and microcalcifications suggested malignancy in nodules with FLUS or FN on FNAC. These additional US findings could improve the diagnostic performance of K-TIRADS.

Purpose: To identify US findings suggestive of malignancy in thyroid nodules with follicular lesions of undetermined significance (FLUS) or follicular neoplasm (FN) on fine-needle aspiration cytology (FNAC) and evaluate the diagnostic performance. Materials and Methods: Seventy FLUS (n = 57) or FN (n = 13) nodules on FNAC that underwent surgical excision between February 2018 and November 2020 were selected. US findings were retrospectively reviewed. Orientation, margin, echogenicity, calcification, additional findings of the rim, echogenicity, heterogeneity of the solid portion, and the ratio of anterior posterior diameter to lateral diameter (criteria) were assessed. The diagnostic performances of US findings, criteria, and the Korean Society of Thyroid Radiology Thyroid Imaging Reporting and Data System (K-TIRADS) were evaluated using logistic regression analysis. Results: Microcalcification, homogeneous solid echotexture, and thickened rims were suggestive of malignancy. Our criteria showed a highest area under the ROC curve (AUC) value of 0.771, sensitivity of 97.14%, accuracy of 77.14%, positive predictive value of 93.33%, negative predictive value of 95.24%, and specificity of 97.14%. The criteria showed a significantly higher AUC value than K-TIRADS. Conclusion US findings of homogenous solid portions, thick rims, and microcalcifications suggested malignancy in nodules with FLUS or FN on FNAC. These additional US findings could improve the diagnostic performance of K-TIRADS.

Purpose: To identify US findings suggestive of malignancy in thyroid nodules with follicular lesions of undetermined significance (FLUS) or follicular neoplasm (FN) on fine-needle aspiration cytology (FNAC) and evaluate the diagnostic performance. Materials and Methods: Seventy FLUS (n = 57) or FN (n = 13) nodules on FNAC that underwent surgical excision between February 2018 and November 2020 were selected. US findings were retrospectively reviewed. Orientation, margin, echogenicity, calcification, additional findings of the rim, echogenicity, heterogeneity of the solid portion, and the ratio of anterior posterior diameter to lateral diameter (criteria) were assessed. The diagnostic performances of US findings, criteria, and the Korean Society of Thyroid Radiology Thyroid Imaging Reporting and Data System (K-TIRADS) were evaluated using logistic regression analysis. Results: Microcalcification, homogeneous solid echotexture, and thickened rims were suggestive of malignancy. Our criteria showed a highest area under the ROC curve (AUC) value of 0.771, sensitivity of 97.14%, accuracy of 77.14%, positive predictive value of 93.33%, negative predictive value of 95.24%, and specificity of 97.14%. The criteria showed a significantly higher AUC value than K-TIRADS. Conclusion US findings of homogenous solid portions, thick rims, and microcalcifications suggested malignancy in nodules with FLUS or FN on FNAC. These additional US findings could improve the diagnostic performance of K-TIRADS.

Chimeric antigen receptor (CAR)-T cell therapy, which has demonstrated remarkable efficacy in hematologic malignancies, is being extended to the treatment of refractory solid tumors, including brain tumors. Lymphodepletion (LD) is an essential preconditioning process that enhances CAR-T efficacy by promoting CAR-T cell expansion and persistence in the body, and has become a standard regimen for hematologic cancers. Recent clinical results of CAR-T therapy for solid tumors, including brain tumors, have shown that cyclophosphamide/fludarabine-based preconditioning has potential benefits and is gradually becoming adopted in solid tumor CAR-T trials. Furthermore, some CAR-T trials for solid tumors are attempting to develop LD regimens optimized specifically for solid tumors, distinct from the standard LD regimens used in hematologic cancers. In contrast, CAR-T therapy targeting brain tumors frequently employs locoregionally repeated administration in tumors or cerebrospinal fluid, resulting in less frequent use of LD compared to other solid tumors. Nevertheless, several clinical studies suggest that LD may still provide potential benefits for CAR-T expansion and improvement in clinical responses in systemic CAR-T administration. The studies presented in this review suggest that while LD can be beneficial for enhancing CAR-T efficacy, considerations must be made regarding its compatibility with the CAR-T administration route, potential excessive activation based on CAR-T structural characteristics, and target expression in normal organs. Additionally, given the unique characteristics of brain tumors, optimized selection of LD agents, as well as dosing and regimens, may be required, highlighting the need for further research.

Purpose: Over the past decade, interest in exosomes as therapeutics has surged. In particular, stem-cell–derived exosomes may be more effective as a treatment for liver disease than the stem cells themselves. We have previously developed human chemically derived hepatic progenitors (hCdHs) from human hepatocytes. hCdHs can differentiate into hepatocytes and cholangiocytes, regenerating the liver in mouse models. In this study, we evaluated the mitigating effects of hCdHs-derived exosomes (hCdHs-exo) on liver damage and compared them with those of exosomes from bone marrow mesenchymal stem cells (BMMSCs-exo). Methods: Exosomes were isolated from hCdHs and BMMSCs by culturing cells in large quantities and separating the exosomes from the culture medium using ultracentrifugation. Isolated exosomes were characterized by various methods before experimental use. In vitro, the ability of exosomes to inhibit activation of hepatic stellate cells (HSCs) by transforming growth factor beta 1 was evaluated. In vivo, exosomes were injected into mice with carbon tetrachloride (CCl4 )-induced liver damage, and their effectiveness in mitigating liver damage was assessed by histological staining and biochemical analysis. Results: The analyses confirmed the successful isolation of exosomes from both cell types. In vitro, hCdHs-exo significantly reduced the levels of transcription factors and activation markers in induced HSCs. In vivo, hCdHs-exo effectively alleviated liver damage caused by CCl4 . Furthermore, both in vitro and in vivo studies confirmed that hCdHs-exo had a greater effect in alleviating liver damage than did BMMSCs-exo. Conclusion These results demonstrate that hCdHs-exo, similarly to hCdHs, have superior efficacy in alleviating liver damage compared with BMMSCs-exo.

Purpose: Over the past decade, interest in exosomes as therapeutics has surged. In particular, stem-cell–derived exosomes may be more effective as a treatment for liver disease than the stem cells themselves. We have previously developed human chemically derived hepatic progenitors (hCdHs) from human hepatocytes. hCdHs can differentiate into hepatocytes and cholangiocytes, regenerating the liver in mouse models. In this study, we evaluated the mitigating effects of hCdHs-derived exosomes (hCdHs-exo) on liver damage and compared them with those of exosomes from bone marrow mesenchymal stem cells (BMMSCs-exo). Methods: Exosomes were isolated from hCdHs and BMMSCs by culturing cells in large quantities and separating the exosomes from the culture medium using ultracentrifugation. Isolated exosomes were characterized by various methods before experimental use. In vitro, the ability of exosomes to inhibit activation of hepatic stellate cells (HSCs) by transforming growth factor beta 1 was evaluated. In vivo, exosomes were injected into mice with carbon tetrachloride (CCl4 )-induced liver damage, and their effectiveness in mitigating liver damage was assessed by histological staining and biochemical analysis. Results: The analyses confirmed the successful isolation of exosomes from both cell types. In vitro, hCdHs-exo significantly reduced the levels of transcription factors and activation markers in induced HSCs. In vivo, hCdHs-exo effectively alleviated liver damage caused by CCl4 . Furthermore, both in vitro and in vivo studies confirmed that hCdHs-exo had a greater effect in alleviating liver damage than did BMMSCs-exo. Conclusion These results demonstrate that hCdHs-exo, similarly to hCdHs, have superior efficacy in alleviating liver damage compared with BMMSCs-exo.

Chimeric antigen receptor (CAR)-T cell therapy, which has demonstrated remarkable efficacy in hematologic malignancies, is being extended to the treatment of refractory solid tumors, including brain tumors. Lymphodepletion (LD) is an essential preconditioning process that enhances CAR-T efficacy by promoting CAR-T cell expansion and persistence in the body, and has become a standard regimen for hematologic cancers. Recent clinical results of CAR-T therapy for solid tumors, including brain tumors, have shown that cyclophosphamide/fludarabine-based preconditioning has potential benefits and is gradually becoming adopted in solid tumor CAR-T trials. Furthermore, some CAR-T trials for solid tumors are attempting to develop LD regimens optimized specifically for solid tumors, distinct from the standard LD regimens used in hematologic cancers. In contrast, CAR-T therapy targeting brain tumors frequently employs locoregionally repeated administration in tumors or cerebrospinal fluid, resulting in less frequent use of LD compared to other solid tumors. Nevertheless, several clinical studies suggest that LD may still provide potential benefits for CAR-T expansion and improvement in clinical responses in systemic CAR-T administration. The studies presented in this review suggest that while LD can be beneficial for enhancing CAR-T efficacy, considerations must be made regarding its compatibility with the CAR-T administration route, potential excessive activation based on CAR-T structural characteristics, and target expression in normal organs. Additionally, given the unique characteristics of brain tumors, optimized selection of LD agents, as well as dosing and regimens, may be required, highlighting the need for further research.

Purpose: Over the past decade, interest in exosomes as therapeutics has surged. In particular, stem-cell–derived exosomes may be more effective as a treatment for liver disease than the stem cells themselves. We have previously developed human chemically derived hepatic progenitors (hCdHs) from human hepatocytes. hCdHs can differentiate into hepatocytes and cholangiocytes, regenerating the liver in mouse models. In this study, we evaluated the mitigating effects of hCdHs-derived exosomes (hCdHs-exo) on liver damage and compared them with those of exosomes from bone marrow mesenchymal stem cells (BMMSCs-exo). Methods: Exosomes were isolated from hCdHs and BMMSCs by culturing cells in large quantities and separating the exosomes from the culture medium using ultracentrifugation. Isolated exosomes were characterized by various methods before experimental use. In vitro, the ability of exosomes to inhibit activation of hepatic stellate cells (HSCs) by transforming growth factor beta 1 was evaluated. In vivo, exosomes were injected into mice with carbon tetrachloride (CCl4 )-induced liver damage, and their effectiveness in mitigating liver damage was assessed by histological staining and biochemical analysis. Results: The analyses confirmed the successful isolation of exosomes from both cell types. In vitro, hCdHs-exo significantly reduced the levels of transcription factors and activation markers in induced HSCs. In vivo, hCdHs-exo effectively alleviated liver damage caused by CCl4 . Furthermore, both in vitro and in vivo studies confirmed that hCdHs-exo had a greater effect in alleviating liver damage than did BMMSCs-exo. Conclusion These results demonstrate that hCdHs-exo, similarly to hCdHs, have superior efficacy in alleviating liver damage compared with BMMSCs-exo.

Chimeric antigen receptor (CAR)-T cell therapy, which has demonstrated remarkable efficacy in hematologic malignancies, is being extended to the treatment of refractory solid tumors, including brain tumors. Lymphodepletion (LD) is an essential preconditioning process that enhances CAR-T efficacy by promoting CAR-T cell expansion and persistence in the body, and has become a standard regimen for hematologic cancers. Recent clinical results of CAR-T therapy for solid tumors, including brain tumors, have shown that cyclophosphamide/fludarabine-based preconditioning has potential benefits and is gradually becoming adopted in solid tumor CAR-T trials. Furthermore, some CAR-T trials for solid tumors are attempting to develop LD regimens optimized specifically for solid tumors, distinct from the standard LD regimens used in hematologic cancers. In contrast, CAR-T therapy targeting brain tumors frequently employs locoregionally repeated administration in tumors or cerebrospinal fluid, resulting in less frequent use of LD compared to other solid tumors. Nevertheless, several clinical studies suggest that LD may still provide potential benefits for CAR-T expansion and improvement in clinical responses in systemic CAR-T administration. The studies presented in this review suggest that while LD can be beneficial for enhancing CAR-T efficacy, considerations must be made regarding its compatibility with the CAR-T administration route, potential excessive activation based on CAR-T structural characteristics, and target expression in normal organs. Additionally, given the unique characteristics of brain tumors, optimized selection of LD agents, as well as dosing and regimens, may be required, highlighting the need for further research.

Background/Aims: To investigate the risk of metabolic syndrome and fatty liver diseases in gastric cancer survivors compared to non-cancer subjects. Methods: The data from the health screening registry of the Gangnam Severance Hospital from 2014–2019 was used. Ninety-one gastric cancer survivors and a propensity-score-matching 445 non-cancer subjects were analyzed. Gastric cancer survivors were divided into those with surgical treatment (OpGC, n=66) and non-surgical treatment (non-OpGC, n=25). Metabolic syndrome, fatty liver by ultrasonography, and metabolic dysfunction-associated fatty liver disease (MAFLD) were assessed. Results: Metabolic syndrome was in 15.4% of gastric cancer survivors (OpGC; 13.6%, non-OpGC; 20.0%). Fatty liver by ultrasonography was in 35.2% in gastric cancer survivors (OpGC; 30.3%, non-OpGC: 48.0%). MAFLD was in 27.5% of gastric cancer survivor (OpGC; 21.2%, non-OpGC; 44.0%). After adjusting for age, sex, smoking, and alcohol, the risk of metabolic syndrome was lower in OpGC than in non-cancer subjects (OR, 0.372; 95% CI, 0.176-0.786, p=0.010). After adjusting, OpGC showed lower risks of fatty liver by ultrasonography (OR, 0.545; 95% CI, 0.306-0.970, p=0.039) and MAFLD (OR, 0.375; 95% CI, 0.197-0.711, p=0.003) than did non-cancer subjects. There were no significant differences in the risks of metabolic syndrome and fatty liver diseases between non-OpGC and non-cancer subjects. Conclusions OpGC showed lower risks of metabolic syndrome, fatty liver by ultrasonography, and MAFLD than non-cancer subjects, but there were no significant differences in the risks between non-OpGC and non-cancer subjects. Further studies on metabolic syndrome and fatty liver diseases in gastric cancer survivors are warranted.