Changes in spatial clusters of cancer incidence and mortality over 15 years in South Korea: Implication to cancer control.

BACKGROUND: The temporal investigation of high-risk areas of cancer incidence and mortality can provide practical implications in cancer control. We aimed to investigate the changes in spatial clusters of incidence and mortality from 1999 through 2013 by major cancer types in South Korea. METHODS: We applied flexible scan statistics to identify spatial clusters of cancer incidence and mortality by three 5-year periods and seven major cancer types using the counts of new cases and deaths and population in 244 districts during 1999-2013. Then, we compared the changes across three periods in the locations of primary clusters of incidence and mortality by cancer types. To explore the determinants that possibly affect cancer cluster areas, we compared geographic characteristics between clustered and non-clustered areas. RESULTS: While incidence clusters for lung, stomach, and liver cancer remained in the same areas over 15 years, mortality clusters were relocated to the areas similar to those of incidence clusters. In contrast, colorectal, breast, cervical, and prostate cancer displayed consistently different locations of clusters over time, indicating the disappearance of existing clusters and the appearance of new clusters. Cluster areas tended to show higher portions of older population, unemployment, smoking, and cancer screening compared to non-cluster areas particularly for mortality. CONCLUSIONS: Our findings of diverse patterns of changes in cancer incidence and mortality clusters over 15 years can indicate the degree of effectiveness in cancer prevention and treatment depending on the area and suggest the need for area-specific applications of different cancer control programs.

Chiral separation and molecular modeling study of decursinol and its derivatives using polysaccharide-based chiral stationary phases.

Plant-based bioactive substances have long been used to treat inflammatory ailments, owing to their low toxicity and cost-effectiveness. To enhance plant treatment by eliminating undesirable isomers, optimizing the chiral separation techniques in pharmaceutical and clinical studies is important. This study reported a simple and effective method for chiral separation of decursinol and its derivatives, which are pyranocoumarin compounds with anti-cancer and anti-inflammatory properties. Baseline separation (Rs >1.5) was achieved using five different polysaccharide-based chiral stationary phases (CSPs) that differed in chiral origin, chiral selector chemistry, and preparation technique. To separate all six enantiomers simultaneously, n-hexane and three alcohol modifiers (ethanol, isopropanol, and n-butanol) were used as mobile phases in the normal-phase mode. The chiral separation ability of each column with various mobile phase compositions was compared and discussed. As a result, amylose-based CSPs with linear alcohol modifiers demonstrated superior resolution. Three cases of elution order reversal caused by modifications of CSPs and alcohol modifiers were observed and thoroughly analyzed. To elucidate the chiral recognition mechanism and enantiomeric elution order (EEO) reversal phenomenon, detailed molecular docking simulations were conducted. The R- and S-enantiomers of decursinol, epoxide, and CGK012 exhibited binding energies of -6.6, -6.3, -6.2, -6.3, -7.3, and -7.5 kcal/mol, respectively. The magnitude of the difference in binding energies was consistent with the elution order and enantioselectivity (α) of the analytes. The molecular simulation results demonstrated that hydrogen bonds, π-π interactions, and hydrophobic interactions have a significant impact on chiral recognition mechanisms. Overall, this study presented a novel and logical approach of optimizing chiral separation techniques in the pharmaceutical and clinical industries. Our findings could be further applied for screening and optimizing enantiomeric separation.

Mohs Micrographic Surgery With Digital Pathology Improves Surgical Quality and Efficiency: A Retrospective Cohort Study.

BACKGROUND: Mohs micrographic surgery, involving pathology of the surgical margin, has the lowest recurrence rate for skin cancer. Moreover, because of technological advances, digital pathology systems are gradually being adopted in hospitals. Yongin Severance Hospital was the first hospital to construct a fully digitalized pathology system in Korea. OBJECTIVE: To evaluate the efficiency and characteristics of the digital pathology system for Mohs micrographic surgery. METHODS: The medical records of 80 patients with skin cancer who underwent Mohs micrographic surgery from March 2020 to August 2022 were analyzed for the number of frozen margins, number of stages, operation time, and recurrence rate to compare cases based on the pathology system. RESULTS: Overall, 23 and 57 patients were examined using the conventional and digital pathology systems, respectively. The mean number of final stages was 0.494 lower ( p -value = .008), the time from the previous to the next stage was 0.687-fold shorter ( p = .002), and the rate of switching from positive to negative margins was 1.990 times higher ( p = .044) in the digital than the conventional group. LIMITATIONS: Retrospective single-center experience; short follow-up time. CONCLUSION: Digital pathology reduces operative time and increases accuracy in Mohs micrographic surgery.

Reasons for Initiation and Regular Use of Heated Tobacco Products among Current and Former Smokers in South Korea: Findings from the 2020 ITC Korea Survey.

South Korea is the world's second-largest heated tobacco product (HTP) market after Japan. HTP sales in South Korea have increased rapidly since May 2017, accounting for 10.6% of the total tobacco market in 2020. Despite this, little is known as to why HTP consumers who were current and former smokers started using HTPs and used them regularly. We analyzed cross-sectional data for 1815 adults (aged 19+) who participated in the 2020 International Tobacco Control (ITC) Korea Survey, of whom 1650 were HTP-cigarette consumers (those who reported smoking cigarettes and using HTPs ≥ weekly) and 165 were exclusive HTP consumers (using HTPs ≥ weekly) who were former or occasional smokers (smoking cigarette < weekly). Respondents were asked to report the reason(s) they used HTPs, with 25 possible reasons for HTP-cigarette consumers and 22 for exclusive HTP consumers. The most common reasons for initiating HTP use among all HTP consumers were out of curiosity (58.9%), family and friends use HTPs (45.5%), and they like the HTP technology (35.9%). The most common reasons for regularly using HTPs among all HTP consumers were that they were less smelly than cigarettes (71.3%), HTPs are less harmful to own health than cigarettes (48.6%), and stress reduction (47.4%). Overall, 35.4% of HTP-cigarette consumers reported using HTPs to quit smoking, 14.7% to reduce smoking but not to quit, and 49.7% for other reasons besides quitting or reducing smoking. In conclusion, several common reasons for initiating and regularly using HTPs were endorsed by all HTP consumers who were smoking, had quit smoking completely, or occasionally smoked. Notably, only about one-third of HTP-cigarette consumers said they were using HTPs to quit smoking, suggesting that most had no intention of using HTPs as an aid to quit smoking in South Korea.

A Standardized Pathology Report for Gastric Cancer: 2nd Edition.

The first edition of 'A Standardized Pathology Report for Gastric Cancer' was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.

A standardized pathology report for gastric cancer: 2nd edition.

The first edition of 'A Standardized Pathology Report for Gastric Cancer' was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.

Intra- and extra-capsular ganglia at the gastrocnemius origin and association with meniscal tears and severity of osteoarthritis of the knee joint.

BACKGROUND: The association between size of ganglia or type of ganglia (intra-articular or extra-articular) and meniscal tears or severity of the osteoarthritis (OA) is not evaluated. PURPOSE: To evaluate the prevalence, size, and location of intra- and extra-capsular ganglia at the gastrocnemius origin and to assess their associations with meniscal injury and grades of OA. MATERIAL AND METHODS: This study included 301 consecutive patients who had knee pain and had undergone magnetic resonance imaging (MRI) of the knee. We evaluated presence of ganglia at the gastrocnemius muscle origin site and diagnosed whether it was an intra-capsular located or mixed-capsular located (intra-capsular and extra-capsular) and then measured the diameter of each ganglion. After two weeks, we evaluated whether articular cartilage injury existed. The presence of a meniscal tear was also recorded. RESULTS: A total of 186 patients (93%) had intra- and extra-capsular ganglia. Intra-capsular ganglia were found in 183 cases (91%) and mixed-capsular ganglia were found in 16 cases (8%). In cases with intra- and extra-capsular ganglia, more meniscal tears were found (P = 0.029). Intra-capsular ganglia showed more meniscal tears (P = 0.021). Intra-capsular ganglia were more likely to have high-grade OA (P = 0.043). Patients who had a meniscal tear displayed larger-sized ganglia, especially of the intra-capsular type (P = 0.044). CONCLUSION: Patients with intra- and extra-capsular ganglia, especially of the intra-capsular type, are more likely to have meniscal injury and more severe OA. Patients with a meniscal tear or OA are more likely to have larger intra- and extra-capsular ganglia, especially of the intra-capsular type.

Changes in Expenditures of the National Health Insurance of Korea during the COVID-19 Pandemic and the Financial Implications Thereof.

As the number of coronavirus disease 2019 (COVID-19) patients increased rapidly, the Korean government decided to pay most of the related medical expenses with finances from the National Health Insurance (NHI). We aimed to document changes in NHI medical expenses during the COVID-19 pandemic period. We also sought to compare how Japan and Taiwan, neighboring countries with NHI systems, responded to COVID-19 and to discuss policy implications.

Awareness of and practice toward cancer prevention recommendations: results of the Korean National Cancer Prevention Awareness and Practice Survey in 2021.

OBJECTIVES: This study reports data regarding the awareness and practice of cancer prevention among Koreans in 2021 and behavioral changes during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We collected Cancer Prevention Awareness and Practice Survey data through face-to-face interview surveys using a structured questionnaire completed by 4,000 randomly selected men and women aged between 20 years and 74 years in 17 provinces. We examined the awareness and practice of 10 cancer prevention recommendations and evaluated their associations with potential risk factors through multiple logistic regression analysis adjusted for age, gender, residence, marital status, education, and income. RESULTS: Eighty percent of participants knew that cancer is preventable, while 45% practiced cancer prevention. Cancer prevention practice tended to be more common among older participants (adjusted odds ratio [aOR], 1.39 per 10-year increment; 95% confidence interval [CI], 1.29 to 1.49) and less common among rural inhabitants (aOR, 0.66; 95% CI, 0.51 to 0.86) than among urban residents and among single people (aOR, 0.55; 95% CI, 0.45 to 0.66) than among married people. Practices were the highest for avoiding burned or charred foods (87.6%) and lowest for vaccination against human papillomavirus (14.5%). Refusal to follow recommendations was most common for avoiding alcohol consumption (7.9%). The most difficult recommendations to follow were (1) regular exercise (57.7%); (2) maintaining a healthy body weight (46.1%); and (3) avoiding alcohol (40.1%). The most significant COVID-19-related changes were less exercise (32.5%) and increased body weight (25.6%). CONCLUSIONS: The awareness of cancer prevention was high, but the practice was low. Recommendations targeting awareness and practice need to be further promoted.

Clinicopathologic characteristics of early-onset colorectal cancer.

PURPOSE: The aim of this study was to analysis of the clinicopathological characteristics and prognosis of colorectal cancer (CRC) under the age of 50 years. METHODS: Between January 2009 and December 2018, 1,126 primary CRC patients were included from National Health Insurance Service Ilsan Hospital. The patients were divided into group 1 (n=111, ≤50 years) and group 2 (n=1,015, >50 years). The clinicopathologic features and prognostic outcomes were compared. In addition, to analyze whether there were any differences of those characteristics in 3 groups, patients aged under 50 years were divided into their 20s, 30s, and 40s. RESULTS: Group 1 had a slightly higher distribution in the left colon and rectum, lower T stage I and higher T stage IV rate, and a significantly higher distribution in stage N2 than group 2 (30.6%:16.3%, P<0.001). Poor histological differentiation of tumors was significantly high in group 1 (P=0.003). The 5-year survival rate for those in their 30s (69.2%) and 40s (91.6%) was higher than those in their 20s who died immediately after surgery (P<0.001). The 5-year disease-free survival rate was also confirmed to be meaningful for each age group, with 0% in their 20s, 53.8% in their 30s, 79.2% in their 40s (P<0.001). CONCLUSION: Although the age was not an independent prognostic factor for overall survival in this study, the early onset group of CRCs is more advanced at the time of diagnosis and has a more aggressive histologic type.

Familial Risk of Renal Cell Cancer and Interaction with Obesity and Hyperglycemia: A Population-Based Study.

PURPOSE: We quantified the familial risk of renal cell cancer (RCC) among first-degree relatives (FDRs) on a population level, and examined interactions between family history and body mass index or blood glucose. MATERIALS AND METHODS: Using the National Health Insurance database, which covers the entire Korean population, and the National Health Screening Program, we constructed a cohort of 5,524,403 individuals with blood-related FDRs and their lifestyle factors from 2002 to 2018. We calculated familial risk using incidence risk ratios (IRRs) with 95% confidence intervals, which compares the risk of individuals with and without FDR. The combined effect and interaction of a given risk factor and family history of RCC were measured by the relative excess risk due to interaction. RESULTS: Individuals with affected FDRs showed a 2.29-fold (95% CI 1.68-3.13) increased risk of disease. Familial risk adjusted for lifestyle factors showed minimal attenuation (IRR 2.25; 95% CI: 1.65-3.08), suggesting that genetic predisposition is the main contributor in the familial aggregation of RCC. Individuals with both a positive family history and overweight/obesity (IRR 3.71, 95% CI 2.50-4.92) or hyperglycemia (IRR 4.52, 95% CI 2.59-6.45) had a significantly higher risk that exceeded the sum of their individual risks, suggesting an interaction that was statistically significant (relative excess risk due to interaction 95% CI: 0.91, -0.21-2.12; 2.21, 0.28-4.14). CONCLUSIONS: Our findings suggest an interaction between genetic and environmental factors, namely obesity and hyperglycemia. Individuals with both factors should be considered a high-risk group and advised to undergo genetic counseling.

Digital Dermatopathology and Its Application to Mohs Micrographic Surgery.

Digital pathology is being gradually adopted in hospitals due to technological advances. We propose that digital pathology can be used in Mohs micrographic surgery (Mohs surgery) to precisely check residual tumor cells in frozen tumor margin tissues. This would aid surgeons and pathologists in accurately recording tumor margins and give patients the benefit of shorter operation time.

Association Between Sleep Duration and Intelligence Quotient in 6-Year-Old Children.

BACKGROUND: Sufficient sleep during childhood is important for cognitive functions such as learning and successful school performance. This study aimed to investigate the effects of sleep duration on the intelligence quotient (IQ) of 6-year-old children and aimed to analyze whether these effects differed by sex. METHODS: The IQ of 538 6-year-old Korean participants from the cohort study, "The Environment and Development of Children," was measured during follow-up using the Korean Educational Developmental Institute's Wechsler Intelligence Scale for Children. The total, verbal, and performance IQ scores were evaluated. The relationship between sleep duration and IQ scores after adjusting for maternal age, maternal educational level, maternal occupation, maternal IQ, exposure to secondhand smoking, gestational age, and monthly age and birth season was also assessed. RESULTS: Longer sleep duration was significantly associated with improved verbal IQ measures (ß 0.55; p value 0.030). After stratifying participants by sex, a significant association was observed between sleep duration and total, verbal, and performance IQ scores in boys (total IQ 2.49, p value 0.012; verbal IQ 0.75, p value: 0.037; performance IQ 0.73, p value 0.048), but not in girls. CONCLUSIONS: The results indicated that only boys show a significant association between IQ scores and sleep duration. These findings support the hypothesis that sleep duration is associated with IQ, in a sex dependent manner. Future studies are needed for a thorough evaluation of the connection between sleep duration and health outcome in young children.

2021 Korean Thyroid Imaging Reporting and Data System and Imaging-Based Management of Thyroid Nodules: Korean Society of Thyroid Radiology Consensus Statement and Recommendations.

Incidental thyroid nodules are commonly detected on ultrasonography (US). This has contributed to the rapidly rising incidence of low-risk papillary thyroid carcinoma over the last 20 years. The appropriate diagnosis and management of these patients is based on the risk factors related to the patients as well as the thyroid nodules. The Korean Society of Thyroid Radiology (KSThR) published consensus recommendations for US-based management of thyroid nodules in 2011 and revised them in 2016. These guidelines have been used as the standard guidelines in Korea. However, recent advances in the diagnosis and management of thyroid nodules have necessitated the revision of the original recommendations. The task force of the KSThR has revised the Korean Thyroid Imaging Reporting and Data System and recommendations for US lexicon, biopsy criteria, US criteria of extrathyroidal extension, optimal thyroid computed tomography protocol, and US follow-up of thyroid nodules before and after biopsy. The biopsy criteria were revised to reduce unnecessary biopsies for benign nodules while maintaining an appropriate sensitivity for the detection of malignant tumors in small (1-2 cm) thyroid nodules. The goal of these recommendations is to provide the optimal scientific evidence and expert opinion consensus regarding US-based diagnosis and management of thyroid nodules.

Root Bark of Morus alba L. and Its Bioactive Ingredient, Ursolic Acid, Suppress the Proliferation of Multiple Myeloma Cells by Inhibiting Wnt/ß-Catenin Pathway.

The root bark of Morus alba L. has cytotoxic activity against several types of cancer cells. However, little is known about its chemopreventive mechanisms and bioactive metabolites. In this study, we showed that M. alba L. root bark extracts (MRBE) suppressed ß-catenin response transcription (CRT), which is aberrantly activated in various cancers, by promoting the degradation of ß-catenin. In addition, MRBE repressed the expression of the ß-catenin/T-cell factor (TCF)-dependent genes, cmyc and cyclin D1, thus inhibiting the proliferation of RPMI-8226 multiple myeloma (MM) cells. MRBE induced apoptosis in MM cells, as evidenced by the increase in the population of annexin VFITC- positive cells and caspase-3/7 activity. We identified ursolic acid in MRBE through LC/mass spectrum (MS) and observed that it also decreased intracellular ß-catenin, c-myc, and cyclin D1 levels. Furthermore, it suppressed the proliferation of RPMI-8226 cells by stimulating cell cycle arrest and apoptosis. These findings suggest that MRBE and its active ingredient, ursolic acid, exert antiproliferative activity by promoting the degradation of ß-catenin and may have significant chemopreventive potential against MM.

The Decursin Analog, CYJ-27, Suppresses Inflammation Via the Downregulation of NF-κB and STAT-1.

CYJ-27, a synthetic analog of decursin, prevents the generation of proinflammatory cytokines and oxidative stress. In this study, the effects of CYJ-27 on the regulation of inducible nitric oxide synthase (iNOS), heme oxygenase (HO)-1, and cyclooxygenase (COX-)2 were characterized in lipopolysaccharide (LPS)-treated human umbilical vein endothelial cells (HUVECs). In addition, the effects of CYJ-27 on the production of iNOS and representative proinflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1ß, were tested in the lung tissues of LPS-treated mice. CYJ-27 promoted the expression of HO-1, suppressed NF-κB-luciferase activity, and reduced COX-2/PGE2 and iNOS/NO, resulting in a diminution in phosphorylated-STAT-1. Furthermore, CYJ-27 promoted the nuclear translocation of Nrf2, enhanced the combination of Nrf2 to antioxidant response elements, and diminished IL-1ß production in LPS-activated HUVECs. CYJ-27-downregulated iNOS/NO expression was rescued after the RNAi suppression of HO-1. In LPS-treated mice, CYJ-27 significantly diminished iNOS production in the lung tissues and TNF-α expression in the bronchoalveolar lavage fluid. These findings indicate that CYJ-27 exerts anti-inflammatory activities by regulating iNOS through downregulation of both NF-κB activation and phosphorylated-STAT-1. Hence, it can act as a template for the development of novel substances to treat inflammatory diseases.

Environmental and Genetic Risk Factors of Congenital Anomalies: an Umbrella Review of Systematic Reviews and Meta-Analyses.

BACKGROUND: The prevalence of congenital anomalies in newborns in South Korea was 272.9 per 100,000 in 2005, and 314.7 per 100,000 in 2006. In other studies, the prevalence of congenital anomalies in South Korea was equivalent to 286.9 per 10,000 livebirths in 2006, while it was estimated 446.3 per 10,000 births during the period from 2008 to 2014. Several systematic reviews and meta-analyses analyzing the factors contributing to congenital anomalies have been reported, but comprehensive umbrella reviews are lacking. METHODS: We searched PubMed, Google Scholar, Cochrane, and EMBASE databases up to July 1, 2019, for systematic reviews and meta-analyses that investigated the effects of environmental and genetic factors on any type of congenital anomalies. We categorized 8 subgroups of congenital anomalies classified according to the 10th revision of the International Statistical Classification of Diseases (ICD-10). Two researchers independently searched the literature, retrieved the data, and evaluated the quality of each study. RESULTS: We reviewed 66 systematic reviews and meta-analyses that investigated the association between non-genetic or genetic risk factors and congenital anomalies. Overall, 269 associations and 128 associations were considered for environmental and genetic risk factors, respectively. Congenital anomalies based on congenital heart diseases, cleft lip and palate, and others were associated with environmental risk factors based on maternal exposure to environmental exposures (air pollution, toxic chemicals), parental smoking, maternal history (infectious diseases during pregnancy, pregestational and gestational diabetes mellitus, and gestational diabetes mellitus), maternal obesity, maternal drug intake, pregnancy through artificial reproductive technologies, and socioeconomic factors. The association of maternal alcohol or coffee consumption with congenital anomalies was not significant, and maternal folic acid supplementation had a preventive effect on congenital heart defects. Genes or genetic loci associated with congenital anomalies included MTHFR, MTRR and MTR, GATA4, NKX2-5, SRD5A2, CFTR, and 1p22 and 20q12 anomalies. CONCLUSION: This study provides a wide perspective on the distribution of environmental and genetic risk factors of congenital anomalies, thus suggesting future studies and providing health policy implications.

Reply to Brzozek et al. Comment on "Choi et al. Cellular Phone Use and Risk of Tumors: Systematic Review and Meta-Analysis. Int. J. Environ. Res. Public Health 2020, 17, 8079".

We appreciate Christopher Brzozek and his colleagues' interest [...].

WNT5A from the fetal liver vascular niche supports human fetal liver hematopoiesis.

The human fetal liver is a critical organ for prenatal hematopoiesis, the study of which offers insights into niche signals that regulate the fates of hematopoietic stem and progenitor cells (HSPCs) during fetal development. Here, we demonstrate that human fetal liver endothelium uniquely supports the maturation and expansion of multilineage HSPCs. Specifically, co-culture of fetal liver-derived immature CD43+CD45- hematopoietic cells with human fetal liver endothelial cells (ECs) led to a profound increase in the numbers of phenotypic CD45+CD34+ HSPCs and multilineage colony-forming progenitors generated in vitro, when compared to co-culture with ECs derived from other organs. We further identified a supportive role for EC-derived WNT5A in this process via gain- and loss-of-function studies within ECs. Our study emphasizes the importance of the organ-specific endothelial niche in supporting hematopoietic development and provides novel insight into signals that may facilitate HSPC expansion in vitro for clinical applications.

Reply to Comment on Choi, Y.-J., et al. Cellular Phone Use and Risk of Tumors: Systematic Review and Meta-Analysis. Int. J. Environ. Res. Public Health 2020, 17, 8079.

We appreciate Frank de Vocht and Martin Röösli's interest [...].