BACKGROUND/OBJECTIVES: This study aimed to use plasma metabolites to identify clusters of breast cancer survivors and to compare their dietary characteristics and health-related factors across the clusters using unsupervised machine learning. SUBJECTS/METHODS: A total of 419 breast cancer survivors were included in this crosssectional study. We considered 30 plasma metabolites, quantified by high-throughput nuclear magnetic resonance metabolomics. Clusters were obtained based on metabolites using 4 different unsupervised clustering methods: k-means (KM), partitioning around medoids (PAM), self-organizing maps (SOM), and hierarchical agglomerative clustering (HAC). The t-test, χ2 test, and Fisher’s exact test were used to compare sociodemographic, lifestyle, clinical, and dietary characteristics across the clusters. P-values were adjusted through a false discovery rate (FDR). RESULTS: Two clusters were identified using the 4 methods. Participants in cluster 2 had lower concentrations of apolipoprotein A1 and large high-density lipoprotein (HDL) particles and smaller HDL particle sizes, but higher concentrations of chylomicrons and extremely large very-low-density-lipoprotein (VLDL) particles and glycoprotein acetyls, a higher ratio of monounsaturated fatty acids to total fatty acids, and larger VLDL particle sizes compared with cluster 1. Body mass index was significantly higher in cluster 2 compared with cluster 1 (FDR adjusted-PKM < 0.001; PPAM = 0.001; PSOM < 0.001; and PHAC = 0.043). CONCLUSION The breast cancer survivors clustered on the basis of plasma metabolites had distinct characteristics. Further prospective studies are needed to investigate the associations between metabolites, obesity, dietary factors, and breast cancer prognosis.

BACKGROUND/OBJECTIVES: Isoflavones are estrogen-like compounds found in plants and their health effects remain equivocal. We investigated dietary isoflavone intake and its associated factors in Korean breast cancer survivors, with a comparison to cancer-free women. SUBJECTS/METHODS: The usual dietary intake of breast cancer survivors (n = 981, mean age 52 yrs) in 9 hospitals between 2012 and 2019 was assessed using 3-day food records or food frequency questionnaires (FFQs). They were age-matched to 2,943 cancer-free women who completed FFQs as part of a nationwide study conducted between 2012 and 2016. We used the flavonoid database of common Korean foods and the Phenol-Explorer database to estimate isoflavone intake. The contribution of each food or food group to the total isoflavone intake was calculated. The adjusted least-squares means of dietary isoflavone intake according to lifestyle and clinical factors were calculated using generalized linear models. RESULTS: Breast cancer survivors had a higher mean dietary isoflavone intake (23.59 mg/day) than cancer-free women (17.81 mg/day). Major food sources, including tofu, soybeans, and doenjang, contributed to over 70% of the isoflavone intake in both groups. When we estimated dietary isoflavone intake according to lifestyle characteristics, isoflavone intake increased with higher scores of adherence to the American Cancer Society dietary guidelines but decreased with increasing body mass index in both groups. Among cancer-free women, dietary isoflavone intake was higher among those who had never smoked and among dietary supplement users. Among breast cancer survivors, dietary isoflavone intakes did not vary with clinical characteristics, including time since surgery and estrogen receptor status. CONCLUSION Breast cancer survivors were more likely to consume isoflavones than agematched cancer-free women. Dietary isoflavone intake was associated with healthy lifestyle characteristics in women both with and without breast cancer. Further research is needed to understand the role of the higher isoflavone intake among breast cancer survivors compared to cancer-free women on their prognosis.

Background: The development of frailty at hospital discharge affects the clinical outcomes in severe coronavirus disease 2019 (COVID-19) survivors who had no frailty before hospitalization. We aimed to describe the prevalence of new frailty using the clinical frailty scale (CFS) and evaluate its associated factors in patients with severe COVID-19 without pre-existing frailty before hospitalization. Methods: We performed a secondary analysis of clinical data from a nationwide retrospective cohort collected from 22 hospitals between January 1, 2020 and August 31, 2021. The patients were at least 19 years old and survived until discharge after admission to the intensive care unit (ICU) because of severe COVID-19. Development of new frailty was defined as a CFS score ≥5 at hospital discharge. Results: Among 669 severe COVID-19 survivors without pre-existing frailty admitted to the ICU, the mean age was 65.2±12.8 years, 62.5% were male, and 50.2% received mechanical ventilation (MV). The mean CFS score at admission was 2.4±0.9, and new frailty developed in 27.8% (186/483). In multivariate analysis, older age, cardiovascular disease, CFS score of 3–4 before hospitalization, increased C-reactive protein level, longer duration of corticosteroid treatment, and use of MV and extracorporeal membrane oxygenation were identified as factors associated with new-onset frailty. Conclusion Our study suggests that new frailty is not uncommon and is associated with diverse factors in survivors of severe COVID-19 without pre-existing frailty.

Background: We investigated whether nutritional intake is associated with physical activity (PA) and handgrip strength (HGS) in individuals with airflow limitation. Methods: This study analyzed data from the 2014 and 2016 Korean National Health and Nutrition Examination Survey. We assessed total protein intake (g/day), caloric intake (kcal/day), and other nutritional intakes, using a 24-hour dietary recall questionnaire. HGS was measured three times for each hand using a digital grip strength dynamometer, and PA was assessed as health-enhancing PA. Airflow limitation was defined as a forced expiratory volume/forced vital capacity ratio of 0.7 in individuals over 40 years of age. Participants were categorized into groups based on their PA levels and HGS measurements: active aerobic PA vs. non-active aerobic PA, and normal HGS vs. low HGS. Results: Among the 622 individuals with airflow limitation, those involved in active aerobic PA and those with higher HGS had notably higher total food, calorie, water, protein, and lipid intake. The correlations between protein and caloric intake with HGS were strong (correlation coefficients=0.344 and 0.346, respectively). The forest plots show that higher intakes of food, water, calories, protein, and lipids are positively associated with active aerobic PA, while higher intakes of these nutrients are inversely associated with low HGS. However, in the multivariate logistic regression analysis, no significant associations were observed between nutritional intake and active aerobic PA or HGS. Conclusion Nutritional intake was found to not be an independent factor associated with PA and HGS. However, the observed correlations suggest potential indirect effects that warrant further investigation.

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: Sarcopenia, a multifactorial disorder involving metabolic disturbance, suggests potential for metabolite biomarkers. Carnitine (CN), essential for skeletal muscle energy metabolism, may be a candidate biomarker. We investigated whether CN metabolites are biomarkers for sarcopenia. Methods: Associations between the CN metabolites identified from an animal model of sarcopenia and muscle cells and sarcopenia status were evaluated in men from an age-matched discovery (72 cases, 72 controls) and a validation (21 cases, 47 controls) cohort. Results: An association between CN metabolites and sarcopenia showed in mouse and cell studies. In the discovery cohort, plasma C5-CN levels were lower in sarcopenic men (P=0.005). C5-CN levels in men tended to be associated with handgrip strength (HGS) (P=0.098) and were significantly associated with skeletal muscle mass (P=0.003). Each standard deviation increase in C5-CN levels reduced the odds of low muscle mass (odd ratio, 0.61; 95% confidence interval [CI], 0.42 to 0.89). The area under the receiver operating characteristic curve (AUROC) of CN score using a regression equation of C5-CN levels, for sarcopenia was 0.635 (95% CI, 0.544 to 0.726). In the discovery cohort, addition of CN score to HGS significantly improved AUROC from 0.646 (95% CI, 0.575 to 0.717; HGS only) to 0.727 (95% CI, 0.643 to 0.810; P=0.006; HGS+CN score). The improvement was confirmed in the validation cohort (AUROC=0.563; 95% CI, 0.470 to 0.656 for HGS; and AUROC=0.712; 95% CI, 0.569 to 0.855 for HGS+CN score; P=0.027). Conclusion C5-CN, indicative of low muscle mass, is a potential circulating biomarker for sarcopenia in men. Further studies are required to confirm these results and explore sarcopenia-related metabolomic changes.

Background/Aims: Early colorectal cancer (ECC) is commonly resected endoscopically. Perforation is a devastating complication of endoscopic resection. We aimed to identify the characteristics and predictive risk factors for perforation related to endoscopic resection of ECC. Methods: This nationwide retrospective multicenter study included patients with ECC who underwent endoscopic resection. We investigated the demographics, endoscopic findings at the time of treatment, and histopathological characteristics of the resected specimens. Logistic regression analysis was used to investigate the clinical factors associated with procedure-related perforations. Survival analysis was conducted to assess the impact of perforation on the overall survival of patients with ECC. Results: This study included 965 participants with a mean age of 63.4 years. The most common endoscopic treatment was conventional endoscopic mucosal resection (n=573, 59.4%), followed by conventional endoscopic submucosal dissection (n=259, 26.8%). Thirty-three patients (3.4%) experienced perforations, most of which were managed endoscopically (n=23/33, 69.7%). Patients who undergo endoscopic submucosal dissection-hybrid and precut endoscopic mucosal resection have a higher risk of perforation than those who undergo conventional endoscopic mucosal resection (odds ratio, 78.65 and 39.72, p<0.05). Procedure-related perforations were not associated with patient survival. Conclusions Perforation after endoscopic resection had no significant impact on the prognosis of ECC. The type of endoscopic resection was a crucial predictor of perforation. Large-scale prospective studies are needed to further investigate endoscopic resection of ECC.

Purpose: Cystic duct cancers (CDCs) have been classified as extrahepatic bile duct cancers or gallbladder cancers (GBCs); however, it is unclear whether their clinical behavior is similar to that of distal extrahepatic bile duct cancers (DBDCs) or GBCs. Materials and Methods: T category of the CDCs was classified using current T category scheme of the GBCs and DBDCs, and clinicopathological factors were compared among 38 CDCs, 345 GBCs, and 349 DBDCs. We modified Nakata’s classifications (type 1, confined within cystic duct [CD]; combined types 2-4, extension beyond CD) and compared them. Results: No significant overall survival (OS) difference was observed between the patients with CDC, GBC, and DBDC. The T category of GBC staging was more accurate at distinguishing OS in patients with CDC than the DBDC staging. Patients with T3 CDC and GBC showed a significant OS difference when using the T category for GBC staging, while those with T1-T2 CDC and GBC showed no significant difference. In contrast, the T category of DBDC staging did not show any significant OS difference between patients with T1-T2 CDC and DBDC or T3 CDC and DBDC. Patients with type 1 CDC had significantly better OS than those with combined types. Conclusion Unlike GBCs and DBDCs, CDCs exhibit distinct clinicopathological characteristics. The OS is better when the CDC confines within the CD, compared to when it extends beyond it. Therefore, we propose a new T category scheme (T1, confined to CD; T2, invaded beyond CD) for better classifying CDCs.

Purpose: Recent development in perioperative treatment of resectable non–small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection. Materials and Methods: Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee. Results: A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors. Conclusion Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.

BACKGROUND/OBJECTIVES: This study aimed to use plasma metabolites to identify clusters of breast cancer survivors and to compare their dietary characteristics and health-related factors across the clusters using unsupervised machine learning. SUBJECTS/METHODS: A total of 419 breast cancer survivors were included in this crosssectional study. We considered 30 plasma metabolites, quantified by high-throughput nuclear magnetic resonance metabolomics. Clusters were obtained based on metabolites using 4 different unsupervised clustering methods: k-means (KM), partitioning around medoids (PAM), self-organizing maps (SOM), and hierarchical agglomerative clustering (HAC). The t-test, χ2 test, and Fisher’s exact test were used to compare sociodemographic, lifestyle, clinical, and dietary characteristics across the clusters. P-values were adjusted through a false discovery rate (FDR). RESULTS: Two clusters were identified using the 4 methods. Participants in cluster 2 had lower concentrations of apolipoprotein A1 and large high-density lipoprotein (HDL) particles and smaller HDL particle sizes, but higher concentrations of chylomicrons and extremely large very-low-density-lipoprotein (VLDL) particles and glycoprotein acetyls, a higher ratio of monounsaturated fatty acids to total fatty acids, and larger VLDL particle sizes compared with cluster 1. Body mass index was significantly higher in cluster 2 compared with cluster 1 (FDR adjusted-PKM < 0.001; PPAM = 0.001; PSOM < 0.001; and PHAC = 0.043). CONCLUSION The breast cancer survivors clustered on the basis of plasma metabolites had distinct characteristics. Further prospective studies are needed to investigate the associations between metabolites, obesity, dietary factors, and breast cancer prognosis.