Background: The objective of this study is to evaluate the diagnostic accuracy of ¹⁸ F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in detecting recurrence in patients with differentiated thyroid cancer (DTC) who have negative whole-body scans (WBSs) but elevated serum thyroglobulin (Tg) or thyroglobulin antibody (TgAb) levels. Methods: This systematic review/meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Diagnostic Test Accuracy criteria (International Prospective Register of Systematic Reviews registration number: CRD42022340924). A comprehensive search of the MEDLINE, EMBASE, and Cochrane databases identified articles reporting the diagnostic accuracy of FDG PET/CT for the detection of recurrence in patients with DTC with negative WBS and elevated serum Tg or TgAb levels published between January 2012 and June 2023. Meta-analyses were performed to determine the diagnostic accuracy of FDG PET/CT on the total target population as well as on subgroups stratified by serum Tg or TgAb, and thyrotropin (TSH) stimulation status at the time of FDG PET/CT. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was applied to evaluate the quality of evidence and the strength of recommendations to facilitate translation of the meta-analysis results into practical recommendations for clinical guidelines. Results: A total of 24 studies involving 1988 patients were included for analysis. The overall pooled sensitivity and specificity values were 0.87 (95% confidence interval [CI] = 0.83–0.92; I ² = 75%) and 0.84 (CI = 0.80–0.89; I ² = 44%), respectively. Subgroup analyses revealed no significant differences in the diagnostic accuracy of FDG PET/CT in patients stratified by serum Tg or TgAb levels, and TSH stimulation status at the time of PET/CT. Treatment plans were changed following FDG PET/CT imaging in 40% (CI = 34–47%; I ² = 39%) of cases. The quality level of evidence for using FDG PET/CT was moderate in both sensitivity and specificity according to the GRADE system. Conclusion: There is moderate quality evidence demonstrating the high diagnostic accuracy of FDG PET/CT in detecting recurrence in patients with DTC with negative WBS and elevated serum Tg or TgAb levels. This evidence corroborates the current guidelines' endorsement of FDG PET/CT as a diagnostic tool in such patients.

Young Joo Park, Eun Kyung Lee, Young Shin Song, Bon Seok Koo, Hyungju Kwon, Keunyoung Kim, Mijin Kim, Bo Hyun Kim, Won Gu Kim, Won Bae Kim, Won Woong Kim, Jung-Han Kim, Hee Kyung Kim, Hee Young Na, Shin Je Moon, Jung-Eun Moon, Sohyun Park, Jun-Ook Park, Ji-In Bang, Kyorim Back, Youngduk Seo, Dong Yeob Shin, Su-Jin Shin, Hwa Young Ahn, So Won Oh, Seung Hoon Woo, Ho-Ryun Won, Chang Hwan Ryu, Jee Hee Yoon, Ka Hee Yi, Min Kyoung Lee, Sang-Woo Lee, Seung Eun Lee, Sihoon Lee, Young Ah Lee, Joon-Hyop Lee, Ji Ye Lee, Jieun Lee, Cho Rok Lee, Dong-Jun Lim, Jae-Yol Lim, Yun Kyung Jeon, Kyong Yeun Jung, Ari Chong, Yun Jae Chung, Chan Kwon Jung, Kwanhoon Jo, Yoon Young Cho, A Ram Hong, Chae Moon Hong, Ho-Cheol Kang, Sun Wook Kim, Woong Youn Chung, Do Joon Park, Dong Gyu Na, Korean Thyroid Association Guideline Committee on the Managements of Thyroid Nodule and Cancer. Int J Thyroidol 2024;17:1-20. https://doi.org/10.11106/ijt.2024.17.1.1

The alteration of the cellular metabolism is a hallmark of glioma. The high glycolytic phenotype is a critical factor in the pathogenesis of high-grade glioma, including glioblastoma multiforme (GBM). GBM has been stratified into three subtypes as the proneural, mesenchymal, and classical subtypes. High glycolytic activity was found in mesenchymal GBM relative to proneural GBM. NADPH oxidase 2 (NOX2) has been linked to cellular metabolism and epithelial-mesenchymal transition (EMT) in tumors. The role of NOX2 in the regulation of the high glycolytic phenotype and the gain of the mesenchymal subtype in glioma remain unclear. Here, our results show that the levels of NOX2 were elevated in patients with GBM. NOX2 induces hexokinase 2 (HK2)-dependent high glycolytic activity in U87MG glioma cells. High levels of NOX2 are correlated with high levels of HK2 and glucose uptake in patients with GBM relative to benign glioma. Moreover, NOX2 increases the expression of mesenchymal-subtype-related genes, including COL5A1 and FN1 in U87MG glioma cells. High levels of NOX2 are correlated with high levels of COL5A1 and the accumulation of extracellular matrix (ECM) in patients with GBM relative to benign glioma. Furthermore, high levels of HK2 are correlated with high levels of COL5A1 in patients with GBM relative to benign glioma. Our results suggest that NOX2-induced high glycolytic activity contributes to the gain of the COL5A1-mediated mesenchymal phenotype in GBM.

Mijin Kim, Ji-In Bang, Ho-Cheol Kang, Sun Wook Kim, Dong Gyu Na, Young Joo Park, Youngduk Seo, Young Shin Song, So Won Oh, Sang-Woo Lee, Eun Kyung Lee, Ji Ye Lee, Dong-Jun Lim, Ari Chong, Yun Jae Chung, Chae Moon Hong, Min Kyoung Lee, Bo Hyun Kim, Korean Thyroid Association Guideline Committee on the Managements of Thyroid Nodule and Cancer. Int J Thyroidol 2024;17:115-46. https://doi.org/10.11106/ijt.2024.17.1.115