Objectives: . Salivary gland tumors present a diagnostic challenge, with preoperative false-negative results frequently leading to an unexpected diagnosis of malignancy after parotidectomy. This study was conducted to explore the clinical utility of preoperative core needle biopsy (CNB) in diagnosing malignancies before primary parotidectomy and to assess the prognostic implications of CNB for parotid gland cancers. Methods: . This retrospective cohort study included 615 patients who underwent preoperative CNB and parotidectomy for primary parotid tumors from 2003 to 2023 at a tertiary referral hospital. Among these patients, 102 who were diagnosed with primary parotid malignancy following parotidectomy were examined regarding survival outcomes. Disease-free survival (DFS) and predictive factors were assessed through univariable and multivariable analyses. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of CNB were determined. These metrics were then compared to those of a separate cohort of 547 patients who underwent ultrasound-guided fine needle aspiration (FNA) and parotidectomy within the same timeframe. Results: . In the CNB group, the 5-year predicted DFS was 86.9% (95% CI, 79.2%–95.3%). Multivariable analysis identified male sex (hazard ratio [HR], 8.48; 95% CI, 1.05–68.76) and a CNB finding of malignancy (HR, 8.20; 95% CI, 1.01–66.15) as factors significantly associated with decreased DFS. CNB demonstrated significantly higher sensitivity (89.0%; 95% CI, 81.2%–94.4%) and NPV (97.6%; 95% CI, 95.7%–98.8%) compared to FNA, which had a sensitivity of 45.2% (95% CI, 33.5%–57.3%) and an NPV of 90.8% (95% CI, 87.7%–93.3%). Conclusion . Preoperative CNB may be predictive of parotid cancer prognosis. Patients receiving a diagnosis of malignancy on preoperative CNB demonstrated a worse prognosis compared to those with a “less-than-malignant” diagnosis. Additionally, CNB exhibited higher sensitivity than FNA in identifying malignancies of the parotid gland.

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/Aims: Hepatocellular carcinoma (HCC) exhibits high de novo recurrence rates post-resection. Current post-surgery recurrence prediction methods are limited, emphasizing the need for reliable biomarkers to assess recurrence risk. We aimed to develop methylation-based markers for classifying HCC patients and predicting their risk of de novo recurrence post-surgery. Methods: In this retrospective cohort study, we analyzed data from HCC patients who underwent surgical resection in Korea, excluding those with recurrence within one year post-surgery. Using the Infinium Methylation EPIC array on 140 samples in the discovery cohort, we classified patients into low- and high-risk groups based on methylation profiles. Distinctive markers were identified through random forest analysis. These markers were validated in the cancer genome atlas (n=217), Validation cohort 1 (n=63) and experimental Validation using a methylation-sensitive high-resolution melting (MS-HRM) assay in Validation cohort 1 and Validation cohort 2 (n=63). Results: The low-risk recurrence group (methylation group 1; MG1) showed a methylation average of 0.73 (95% confidence interval [CI] 0.69–0.77) with a 23.5% recurrence rate, while the high-risk group (MG2) had an average of 0.17 (95% CI 0.14–0.20) with a 44.1% recurrence rate (P<0.03). Validation confirmed the applicability of methylation markers across diverse populations, showing high accuracy in predicting the probability of HCC recurrence risk (area under the curve 96.8%). The MS-HRM assay confirmed its effectiveness in predicting de novo recurrence with 95.5% sensitivity, 89.7% specificity, and 92.2% accuracy. Conclusions Methylation markers effectively classified HCC patients by de novo recurrence risk, enhancing prediction accuracy and potentially offering personalized management strategies.

Background: Infantile hemangioma (IH) is a common benign vascular tumor that occurs during infancy. Oral propranolol is used as a first-line treatment. However, standardized guidelines for evaluating treatment efficacy, particularly the appropriate timing and parameters for Doppler ultrasound (US), have not been established. This study reports on the evaluation of therapeutic efficacy of oral propranolol solution in IH patients using Doppler US, and aims to propose the appropriate timing and parameters for using Doppler US based on this experience. Methods: A retrospective analysis was conducted on 120 patients with IH who were treated with oral propranolol solution and maintained for over 6 months from May 2017 to April 2023. Doppler US evaluation of IH was performed at diagnosis, 1-2 and 6-12 months after treatment initiation, and 6 months post-therapy cessation. A complete response (CR) was identified as a reduction in vascularity along with a decrease in longest diameter (LD) or thickness of 50% or more. Recurrence was evaluated based on increased vascularity or size 6 months after treatment discontinuation. Results: Of 120 patients with IH, 82 females and 38 males were analyzed. IH was first detected at a median age of 12 days (range, 1-240 days), and treatment began at 76 days (range, 27-570 days), continuing for an average of 10.4 months (range, 5-24 months). Initial Doppler US measurements showed an LD of 2.65±1.52 cm and a thickness of 0.79±0.55 cm, with prominent vascularity. After 1-2 months of treatment, LD and thickness decreased by 12.9% and 25.9%, respectively. By 6-12 months, reductions reached 37.2% and 53.6%. CR occurred in 77 patients (64.2%) after 6-12 months of treatment. Eleven patients (9.2%) experienced a recurrence. Conclusion Doppler US is a valuable modality for evaluating the characteristics, treatment response, and recurrence of IH treated with oral propranolol.

Background: To identify the optimal surgical technique for single-level anterior cervical discectomy and fusion (ACDF), this study compared surgical outcomes and incidence of adjacent segment degeneration (ASD) in patients undergoing single-level ACDF using cage alone single-level fusion and plate fixation techniques. Methods: This single-center retrospective study (2003–2018) included patients who underwent single-level ACDF with either plate fixation (PLATE) or cage (CAGE) alone. The radiologic and clinical outcomes between the 2 surgical groups were compared over a 4-year follow-up period. Outcomes of interest included parameters related to range of motion, sagittal alignment, as well as fusion, subsidence, and ASD rates. Clinical outcomes were evaluated using the Neck Disability Index (NDI) and visual analog scale (VAS) for pain. Dysphagia and hoarseness rates were estimated based on medical records. Results: Forty-seven patients were included (n=17 in CAGE group). In the CAGE group, 94.1% of the patients had Bridwell grade 1 or 2, compared to 83.3% in the PLATE group (p = 0.396). Subsidence occurred in 12.5% and 3.6% of the CAGE and PLATE cases, respectively (p = 0.543). Segmental kyphosis progressed in the CAGE group compared to the PLATE group at 12, 24, and 48 months (p < 0.001). Radiographic ASD was observed in 41.2% and 30.0% of patients in the CAGE and PLATE groups, respectively, with a higher incidence in the upper segments for both groups. Preoperative NDI scores were similar between the groups; however, postoperatively, the CAGE group had significantly lower NDI scores (3.50 ± 2.74 vs. 8.00 ± 5.81) at 4 years (p = 0.020). Neck pain VAS scores also showed significant improvement in the CAGE group (2.33 ± 2.94) compared with that in the PLATE group (3.07 ± 2.31) at 4 years (p = 0.045). Both groups showed comparable arm pain VAS scores at 2 and 4 years postoperatively. Postoperative dysphagia occurred in 1 patient in the PLATE group, resolving almost completely by 1 year. Conclusions Single-level ACDF using a cage alone technique demonstrated favorable radiologic and clinical outcomes overall compared to plate-augmented ACDF. However, plate augmentation is recommended for patients with severe cervical kyphosis or those at high risk of subsidence.

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.

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Background: Antithyroid drug (ATD) treatment is the preferred initial treatment for Graves’ disease (GD) in South Korea, despite higher treatment failure rates than radioactive iodine (RAI) therapy or thyroidectomy. This study aimed to evaluate the incidence of treatment failure associated with the primary modalities for GD treatment in real-world practice. Methods: We included 452,001 patients diagnosed with GD between 2004 and 2020 from the Korean National Health Insurance Service-National Health Information Database. Treatment failure was defined as switching from ATD, RAI, or thyroidectomy treatments, and for ATD specifically, inability to discontinue medication for over 2 years. Results: Mean age was 46.2 years, with females constituting 70.8%. Initial treatments for GD included ATDs (98.0%), thyroidectomy (1.3%), and RAI (0.7%), with a noted increment in ATD application from 96.2% in 2004 to 98.8% in 2020. During a median follow- up of 8.5 years, the treatment failure rates were 58.5% for ATDs, 21.3% for RAI, and 2.1% for thyroidectomy. Multivariate analysis indicated that the hazard ratio for treatment failure with ATD was 2.81 times higher than RAI. RAI treatments ≥10 mCi had 37% lower failure rates than doses <10 mCi. Conclusion ATDs are the most commonly used for GD in South Korea, followed by thyroidectomy and RAI. Although the risk of treatment failure for ATD is higher than that of RAI therapy, initial RAI treatment in South Korea is relatively limited compared to that in Western countries. Further studies are required to evaluate the cause of low initial RAI treatment rates in South Korea.

Background/Aims: The Korean guidelines for Helicobacter pylori treatment were revised in 2020, however, the extent of adherence to these guidelines in clinical practice remains unclear. Herein, we initiated a prospective, nationwide, multicenter registry study in 2021 to evaluate the current management of H.pylori infection in Korea. Methods: This interim report describes the adherence to the revised guidelines and their impact on firstline eradication rates. Data on patient demographics, diagnoses, treatments, and eradication outcomes were collected using a web-based electronic case report form. Results: A total of 7,261 patients from 66 hospitals who received first-line treatment were analyzed.The modified intention-to-treat eradication rate for first-line treatment was 81.0%, with 80.4% of the prescriptions adhering to the revised guidelines. The most commonly prescribed regimen was the 14-day clarithromycin-based triple therapy (CTT; 42.0%), followed by tailored therapy (TT; 21.2%), 7-day CTT (14.1%), and 10-day concomitant therapy (CT; 10.1%). Time-trend analysis demonstrated significant increases in guideline adherence and the use of 10-day CT and TT, along with a decrease in the use of 7-day CTT (all p<0.001). Multivariate logistic regression analysis revealed that guideline adherence was significantly associated with first-line eradication success (odds ratio, 2.03; 95% confidence interval, 1.61 to 2.56; p<0.001). Conclusions The revised guidelines for the treatment of H. pylori infection have been increasingly adopted in routine clinical practice in Korea, which may have contributed to improved first-line eradication rates. Notably, the 14-day CTT, 10-day CT, and TT regimens are emerging as the preferred first-line treatment options among Korean physicians.