Background: Studies on predictive markers of insulin resistance (IR) and elevated liver transaminases in children and adolescents are limited. We evaluated the predictive capabilities of the single-point insulin sensitivity estimator (SPISE) index, metabolic score for insulin resistance (METS-IR), homeostasis model assessment of insulin resistance (HOMA-IR), the triglyceride (TG)/ high-density lipoprotein cholesterol (HDL-C) ratio, and the triglyceride-glucose index (TyG) for IR and alanine aminotransferase (ALT) elevation in this population. Methods: Data from 1,593 participants aged 10 to 18 years were analyzed using a nationwide survey. Logistic regression analysis was performed with IR and ALT elevation as dependent variables. Receiver operating characteristic (ROC) curves were generated to assess predictive capability. Proportions of IR and ALT elevation were compared after dividing participants based on parameter cutoff points. Results: All parameters were significantly associated with IR and ALT elevation, even after adjusting for age and sex, and predicted IR and ALT elevation in ROC curves (all P<0.001). The areas under the ROC curve of SPISE and METS-IR were higher than those of TyG and TG/HDL-C for predicting IR and were higher than those of HOMA-IR, TyG, and TG/HDL-C for predicting ALT elevation. The proportions of individuals with IR and ALT elevation were higher among those with METS-IR, TyG, and TG/ HDL-C values higher than the cutoff points, whereas they were lower among those with SPISE higher than the cutoff point. Conclusion SPISE and METS-IR are superior to TG/HDL-C and TyG in predicting IR and ALT elevation. Thus, this study identified valuable predictive markers for young individuals.

Purpose: This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea. Materials and Methods: Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response. Results: Thirteen of the 29 patients (44.8%) achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression. Conclusion This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles.

Background/Aims: Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC. Methods: We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data. Results: Tumors predominantly exhibited TERT-pro mutations (26.0% vs. 0%) and HBV-TERT integration (37.0% vs. 3.0%) compared to non-tumorous tissues. While TERT-pro mutations increased with age in both sexes, younger males (≤60 years) showed marked predominance compared to younger females. Males had significantly more HBV integrations at younger ages, while females initially had fewer integrations that gradually increased with age. Younger males' integrations showed significantly greater enrichment in the TERT locus compared to younger females, alongside a preference for promoters, PreS/S regions, and CpG islands. Overall, TERT genetic alterations were significantly sex-differential in younger individuals (75.3% in males vs. 23.1% in females) but not in older individuals (76.9% vs. 83.3%, respectively). These alterations were associated with increased TERT expression. The skewed TERT abnormalities in younger males were further corroborated by independent scRNA-seq data. Conclusions Our findings highlight the critical role of TERT alterations and HBV integration patterns in the male predominance of HCC incidence among younger HBV carriers, offering insights for future exploration to optimize sex-specific patient care and HCC surveillance strategies.

Purpose: This study evaluated the postoperative quality of life (QoL) after various types of gastrectomy for gastric cancer. Materials and Methods: A multicenter prospective observational study was conducted in Korea using the Korean Quality of Life in Stomach Cancer Patients Study (KOQUSS)-40, a new QoL assessment tool focusing on postgastrectomy syndrome. Overall, 496 patients with gastric cancer were enrolled, and QoL was assessed at 5 time points: preoperatively and at 1, 3, 6, and 12 months after surgery. Results: Distal gastrectomy (DG) and pylorus-preserving gastrectomy (PPG) showed significantly better outcomes than total gastrectomy (TG) and proximal gastrectomy (PG) with regard to total score, indigestion, and dysphagia. DG, PPG, and TG also showed significantly better outcomes than PG in terms of dumping syndrome and worry about cancer. Postoperative QoL did not differ significantly according to anastomosis type in DG, except for Billroth I anastomosis, which achieved better bowel habit change scores than the others. No domains differed significantly when comparing double tract reconstruction and esophagogastrostomy after PG. The total QoL score correlated significantly with postoperative body weight loss (more than 10%) and extent of resection (P<0.05 for both).Reflux as assessed by KOQUSS-40 did not correlate significantly with reflux observed on gastroscopy 1 year postoperatively (P=0.064). Conclusions Our prospective observation using KOQUSS-40 revealed that DG and PPG lead to better QoL than TG and PG. Further study is needed to compare postoperative QoL according to anastomosis type in DG and PG.

Purpose: Developmentally regulated GTP-binding protein 2 (DRG2) regulates microtubule dynamics and G2/M arrest during docetaxel treatment. Poly ADP-ribose polymerase (PARP) acts as an important repair system for DNA damage caused by docetaxel treatment. This study investigated whether DRG2 expression affects response to PARP inhibitors (olaparib) using prostate cancer cell lines PC3, DU145, LNCaP-FGC, and LNCaP-LN3. Materials and Methods: The cell viability and DRG2 expression levels were assessed using colorimetric-based cell viability assay and western blot. Cells were transfected with DRG2 siRNA, and pcDNA6/V5-DRG2 was used to overexpress DRG2. Flow cytometry was applied for cell cycle assay and apoptosis analysis using the Annexing V cell death assay. Results: The expression of DRG2 was highest in LNCaP-LN3 and lowest in DU145 cells. Expressions of p53 in PC3, DU145, and the two LNCaP cell lines were null-type, high-expression, and medium-expression, respectively. In PC3 (DRG2 high, p53 null) cells, docetaxel increased G2/M arrest without apoptosis; however, subsequent treatment with olaparib promoted apoptosis. In DU145 and LNCaP-FGC (DRG2 low), docetaxel increased sub-G1 but not G2/M arrest and induced apoptosis, whereas olaparib had no additional effect. In LNCaP-LN3 (DRG2 high, p53 wild-type), docetaxel increased sub-G1 and G2/M arrest, furthermore olaparib enhanced cell death. Docetaxel and olaparib combination treatment had a slight effect on DRG2 knockdown PC3, but increased apoptosis in DRG2-overexpressed DU145 cells. Conclusions DRG2 and p53 expressions play an important role in prostate cancer cell lines treated with docetaxel, and DRG2 levels can predict the response to PARP inhibitors.

Background: Studies on predictive markers of insulin resistance (IR) and elevated liver transaminases in children and adolescents are limited. We evaluated the predictive capabilities of the single-point insulin sensitivity estimator (SPISE) index, metabolic score for insulin resistance (METS-IR), homeostasis model assessment of insulin resistance (HOMA-IR), the triglyceride (TG)/ high-density lipoprotein cholesterol (HDL-C) ratio, and the triglyceride-glucose index (TyG) for IR and alanine aminotransferase (ALT) elevation in this population. Methods: Data from 1,593 participants aged 10 to 18 years were analyzed using a nationwide survey. Logistic regression analysis was performed with IR and ALT elevation as dependent variables. Receiver operating characteristic (ROC) curves were generated to assess predictive capability. Proportions of IR and ALT elevation were compared after dividing participants based on parameter cutoff points. Results: All parameters were significantly associated with IR and ALT elevation, even after adjusting for age and sex, and predicted IR and ALT elevation in ROC curves (all P<0.001). The areas under the ROC curve of SPISE and METS-IR were higher than those of TyG and TG/HDL-C for predicting IR and were higher than those of HOMA-IR, TyG, and TG/HDL-C for predicting ALT elevation. The proportions of individuals with IR and ALT elevation were higher among those with METS-IR, TyG, and TG/ HDL-C values higher than the cutoff points, whereas they were lower among those with SPISE higher than the cutoff point. Conclusion SPISE and METS-IR are superior to TG/HDL-C and TyG in predicting IR and ALT elevation. Thus, this study identified valuable predictive markers for young individuals.

Purpose: This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea. Materials and Methods: Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response. Results: Thirteen of the 29 patients (44.8%) achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression. Conclusion This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles.

Background/Aims: Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC. Methods: We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data. Results: Tumors predominantly exhibited TERT-pro mutations (26.0% vs. 0%) and HBV-TERT integration (37.0% vs. 3.0%) compared to non-tumorous tissues. While TERT-pro mutations increased with age in both sexes, younger males (≤60 years) showed marked predominance compared to younger females. Males had significantly more HBV integrations at younger ages, while females initially had fewer integrations that gradually increased with age. Younger males' integrations showed significantly greater enrichment in the TERT locus compared to younger females, alongside a preference for promoters, PreS/S regions, and CpG islands. Overall, TERT genetic alterations were significantly sex-differential in younger individuals (75.3% in males vs. 23.1% in females) but not in older individuals (76.9% vs. 83.3%, respectively). These alterations were associated with increased TERT expression. The skewed TERT abnormalities in younger males were further corroborated by independent scRNA-seq data. Conclusions Our findings highlight the critical role of TERT alterations and HBV integration patterns in the male predominance of HCC incidence among younger HBV carriers, offering insights for future exploration to optimize sex-specific patient care and HCC surveillance strategies.

Background: Studies on predictive markers of insulin resistance (IR) and elevated liver transaminases in children and adolescents are limited. We evaluated the predictive capabilities of the single-point insulin sensitivity estimator (SPISE) index, metabolic score for insulin resistance (METS-IR), homeostasis model assessment of insulin resistance (HOMA-IR), the triglyceride (TG)/ high-density lipoprotein cholesterol (HDL-C) ratio, and the triglyceride-glucose index (TyG) for IR and alanine aminotransferase (ALT) elevation in this population. Methods: Data from 1,593 participants aged 10 to 18 years were analyzed using a nationwide survey. Logistic regression analysis was performed with IR and ALT elevation as dependent variables. Receiver operating characteristic (ROC) curves were generated to assess predictive capability. Proportions of IR and ALT elevation were compared after dividing participants based on parameter cutoff points. Results: All parameters were significantly associated with IR and ALT elevation, even after adjusting for age and sex, and predicted IR and ALT elevation in ROC curves (all P<0.001). The areas under the ROC curve of SPISE and METS-IR were higher than those of TyG and TG/HDL-C for predicting IR and were higher than those of HOMA-IR, TyG, and TG/HDL-C for predicting ALT elevation. The proportions of individuals with IR and ALT elevation were higher among those with METS-IR, TyG, and TG/ HDL-C values higher than the cutoff points, whereas they were lower among those with SPISE higher than the cutoff point. Conclusion SPISE and METS-IR are superior to TG/HDL-C and TyG in predicting IR and ALT elevation. Thus, this study identified valuable predictive markers for young individuals.

Purpose: This study evaluated the postoperative quality of life (QoL) after various types of gastrectomy for gastric cancer. Materials and Methods: A multicenter prospective observational study was conducted in Korea using the Korean Quality of Life in Stomach Cancer Patients Study (KOQUSS)-40, a new QoL assessment tool focusing on postgastrectomy syndrome. Overall, 496 patients with gastric cancer were enrolled, and QoL was assessed at 5 time points: preoperatively and at 1, 3, 6, and 12 months after surgery. Results: Distal gastrectomy (DG) and pylorus-preserving gastrectomy (PPG) showed significantly better outcomes than total gastrectomy (TG) and proximal gastrectomy (PG) with regard to total score, indigestion, and dysphagia. DG, PPG, and TG also showed significantly better outcomes than PG in terms of dumping syndrome and worry about cancer. Postoperative QoL did not differ significantly according to anastomosis type in DG, except for Billroth I anastomosis, which achieved better bowel habit change scores than the others. No domains differed significantly when comparing double tract reconstruction and esophagogastrostomy after PG. The total QoL score correlated significantly with postoperative body weight loss (more than 10%) and extent of resection (P<0.05 for both).Reflux as assessed by KOQUSS-40 did not correlate significantly with reflux observed on gastroscopy 1 year postoperatively (P=0.064). Conclusions Our prospective observation using KOQUSS-40 revealed that DG and PPG lead to better QoL than TG and PG. Further study is needed to compare postoperative QoL according to anastomosis type in DG and PG.