MBD2 couples DNA methylation to transposable element silencing during male gametogenesis.

DNA methylation is an essential component of transposable element (TE) silencing, yet the mechanism by which methylation causes transcriptional repression remains poorly understood1-5. Here we study the Arabidopsis thaliana Methyl-CpG Binding Domain (MBD) proteins MBD1, MBD2 and MBD4 and show that MBD2 acts as a TE repressor during male gametogenesis. MBD2 bound chromatin regions containing high levels of CG methylation, and MBD2 was capable of silencing the FWA gene when tethered to its promoter. MBD2 loss caused activation at a small subset of TEs in the vegetative cell of mature pollen without affecting DNA methylation levels, demonstrating that MBD2-mediated silencing acts strictly downstream of DNA methylation. TE activation in mbd2 became more significant in the mbd5 mbd6 and adcp1 mutant backgrounds, suggesting that MBD2 acts redundantly with other silencing pathways to repress TEs. Overall, our study identifies MBD2 as a methyl reader that acts downstream of DNA methylation to silence TEs during male gametogenesis.

ACD15, ACD21, and SLN regulate the accumulation and mobility of MBD6 to silence genes and transposable elements.

DNA methylation mediates silencing of transposable elements and genes in part via recruitment of the Arabidopsis MBD5/6 complex, which contains the methyl-CpG binding domain (MBD) proteins MBD5 and MBD6, and the J-domain containing protein SILENZIO (SLN). Here, we characterize two additional complex members: α-crystalline domain (ACD) containing proteins ACD15 and ACD21. We show that they are necessary for gene silencing, bridge SLN to the complex, and promote higher-order multimerization of MBD5/6 complexes within heterochromatin. These complexes are also highly dynamic, with the mobility of MBD5/6 complexes regulated by the activity of SLN. Using a dCas9 system, we demonstrate that tethering the ACDs to an ectopic site outside of heterochromatin can drive a massive accumulation of MBD5/6 complexes into large nuclear bodies. These results demonstrate that ACD15 and ACD21 are critical components of the gene-silencing MBD5/6 complex and act to drive the formation of higher-order, dynamic assemblies at CG methylation (meCG) sites.

ACD15, ACD21 and SLN regulate accumulation and mobility of MBD6 to silence genes and transposable elements.

DNA methylation mediates silencing of transposable elements and genes in part via recruitment of the Arabidopsis MBD5/6 complex, which contains the methyl-CpG-binding domain (MBD) proteins MBD5 and MBD6, and the J-domain containing protein SILENZIO (SLN). Here we characterize two additional complex members: α-crystalline domain containing proteins ACD15 and ACD21. We show that they are necessary for gene silencing, bridge SLN to the complex, and promote higher order multimerization of MBD5/6 complexes within heterochromatin. These complexes are also highly dynamic, with the mobility of complex components regulated by the activity of SLN. Using a dCas9 system, we demonstrate that tethering the ACDs to an ectopic site outside of heterochromatin can drive massive accumulation of MBD5/6 complexes into large nuclear bodies. These results demonstrate that ACD15 and ACD21 are critical components of gene silencing complexes that act to drive the formation of higher order, dynamic assemblies.

The Epidemiological and Clinical Characteristics of the Largest Outbreak of Enterohemorrhagic Escherichia coli in Korea.

BACKGROUND: The largest outbreak of enterohemorrhagic Escherichia coli (EHEC) O157:H7 occurred at a preschool in South Korea from June 12 to 29, 2020. This study aimed to analyze the epidemiological and clinical characteristics of EHEC infection in this outbreak. METHODS: Epidemiological investigation was performed on all 184 children and 19 workers at the preschool using a standard questionnaire to assess symptoms, food intake, attendance, and special activity history. Pulsed-field gel electrophoresis analysis of confirmed cases was performed to determine genetic relevance. RESULTS: During this outbreak, 103 children were affected, whereas only one infection was identified in adults. Of the 103 pediatric patients, 85 had symptoms (82.5%), including diarrhea, abdominal pain, bloody stool, fever, and vomiting. Thirty-two patients (31.1%) were hospitalized, 15 (14.6%) were diagnosed with hemolytic uremic syndrome, and 4 (3.9%) received dialysis treatment. Pulsed-field gel electrophoresis analysis identified 4 genotypes with high genetic relevance (92.3%). Epidemiological investigation revealed that this outbreak might have occurred from ingesting foods stored in a refrigerator with a constant temperature above 10°C, which was conducive to bacterial growth. Despite several measures after outbreak recognition, new infections continued to appear. Therefore, the preschool was forced to close on June 19 to prevent further person-to-person transmission. CONCLUSION: Our findings from the response to the largest outbreak will help prepare countermeasures against future EHEC outbreak.

Age at menarche of adolescent girls and the neighbourhood socioeconomic status of their school area.

PURPOSE: To assess the association between abnormal timing of menarche among adolescent girls and neighbourhood socioeconomic status of their school area. MATERIALS AND METHODS: Our analysis included 187,024 girls aged 15-18 years from the Korea Youth Risk Behaviour Web-Based Survey (KYRBS) from 2007 to 2015. Early and late menarche were defined as menarche before 11 years and no menarche by age 14 years, respectively. The deprivation index values for the areas where the schools were located were used as an indicator of neighbourhood socioeconomic status based on the 2005 national census data. We calculated odds ratios (OR) for early and late menarche using a multinomial logistic regression model. Covariates included body mass index, parental education, single or stepparents, siblings, household wealth, year of birth, survey year, and urbanisation. RESULTS: Mean age at menarche was 12 years. The overall proportions of early and late menarche were 11.3% and 3.3%, respectively. When divided into four quartile groups based on the socioeconomic deprivation index, 11.3% of girls in the most deprived quartile and 10.6% in the least deprived area showed early menarche. The prevalence of late menarche did not differ across the deprivation index quartiles of school area. Attendance at schools located in highly deprived areas was associated with up to 10% higher risk of early menarche. This positive association was not evident for late menarche. CONCLUSION: Among contemporary Korean girls, socioeconomic deprivation of the school area was associated with earlier puberty. This finding highlights the potential role of the socioeconomic environment of schools in women's lifetime health.

Single-nucleus RNA-seq reveals that MBD5, MBD6, and SILENZIO maintain silencing in the vegetative cell of developing pollen.

Silencing of transposable elements (TEs) drives the evolution of numerous redundant mechanisms of transcriptional regulation. Arabidopsis MBD5, MBD6, and SILENZIO act as TE repressors downstream of DNA methylation. Here, we show, via single-nucleus RNA-seq of developing male gametophytes, that these repressors are critical for TE silencing in the pollen vegetative cell, a companion cell important for fertilization that undergoes chromatin decompaction. Instead, other silencing mutants (met1, ddm1, mom1, morc) show loss of silencing in all pollen nucleus types and somatic cells. We show that TEs repressed by MBD5/6 gain chromatin accessibility in wild-type vegetative nuclei despite remaining silent, suggesting that loss of DNA compaction makes them sensitive to loss of MBD5/6. Consistently, crossing mbd5/6 to histone 1 mutants, which have decondensed chromatin in leaves, reveals derepression of MBD5/6-dependent TEs in leaves. MBD5/6 and SILENZIO thus act as a silencing system particularly important when chromatin compaction is compromised.

A Comparative Analysis of Influenza-Associated Disease Burden with Different Influenza Vaccination Strategies for the Elderly Population in South Korea.

Influenza affects all age groups, but the risk of hospitalization and death due to influenza is strongly age-related and is at its highest among the elderly aged 65 years and older. The objective of this study is to compare the differences in influenza-associated disease burden under three different influenza vaccination strategies-the standard-dose quadrivalent influenza vaccine (QIV), high-dose QIV (HD-QIV), and MF59®-adjuvanted QIV (aQIV)-for the elderly population aged 65 years and older in South Korea. A one-year decision-tree model was developed to compare influenza disease burdens. The input data for the model were obtained from published literature reviews and surveillance data from the Korea Disease Control and Prevention Agency (KDCA). The analysis indicated that aQIV is more effective than QIV, preventing 35,390 influenza cases, 1602 influenza-associated complications, 709 influenza-associated hospitalizations, and 145 influenza-associated deaths annually. Additionally, aQIV, when compared to HD-QIV, also reduced the influenza-associated burden of disease, preventing 7247 influenza cases, 328 influenza-associated complications, 145 influenza-associated hospitalizations, and 30 influenza-associated deaths annually. Switching the vaccination strategy from QIV to aQIV is predicted to reduce the influenza-associated disease burden for the elderly in South Korea. The public health gains from aQIV and HD-QIV are expected to be comparable. Future studies comparing the effectiveness of the vaccines will further inform future vaccination strategies for the elderly in South Korea.

Cost-Effectiveness of Influenza Vaccination Strategies in Adults: Older Adults Aged ≥65 Years, Adults Aged 50-64 Years, and At-Risk Adults Aged 19-64 Years.

The high disease burden of influenza in elderly and chronically ill adults may be due to the suboptimal effectiveness and mismatch of the conventional trivalent influenza vaccine (TIV). This study evaluated the cost-effectiveness of quadrivalent (QIV), adjuvanted trivalent (ATIV), and high-dose quadrivalent (HD-QIV) vaccines versus TIV used under the current Korean National Immunization Program (NIP) in older adults aged ≥65 years. We also evaluated the cost-effectiveness of programs for at-risk adults aged 19-64 and adults aged 50-64. A one-year static population model was used to compare the costs and outcomes of alternative vaccination programs in each targeted group. Influenza-related parameters were derived from the National Health Insurance System claims database; other inputs were extracted from the published literature. Incremental cost-effectiveness ratios (ICERs) were assessed from a societal perspective. In the base case analysis (older adults aged ≥65 years), HD-QIV was superior, with the lowest cost and highest utility. Compared with TIV, ATIV was cost-effective (ICER $34,314/quality-adjusted life-year [QALY]), and QIV was not cost-effective (ICER $46,486/QALY). The cost-effectiveness of HD-QIV was robust for all parameters except for vaccine cost. The introduction of the influenza NIP was cost-effective or even cost-saving for the remaining targeted gr3oups, regardless of TIV or QIV.

Trends in recent waterborne and foodborne disease outbreaks in South Korea, 2015-2019.

OBJECTIVE: This study analyzed trends in foodborne and waterborne diseases in South Korea between 2015 and 2019. METHODS: The data consisted of information on outbreaks of waterborne and foodborne infectious diseases reported through the Korea Centers for Disease Control and Prevention (KCDC) system. We analyzed the trends and epidemiological aspects of outbreaks by month, place of occurrence, and causative pathogens in this observational study. RESULTS: The number of outbreaks has steadily increased over the last 5 years, but the number of cases per outbreak has followed a decreasing trend. Incidence at daycare centers and preschools has been steadily increasing over consecutive years. CONCLUSION: The steady number of patients and decreasing number of cases per outbreak, even as the number of outbreaks has been increasing, suggest that the KCDC's professional management system is operating effectively. It is necessary to continue improving the objectivity and efficiency of the management system and to carefully examine the increasing number of outbreaks in smaller-scale group catering facilities, such as daycare centers and preschools. Outbreaks can be prevented by closely examining those caused by unidentified pathogens and group outbreaks caused by other diseases, identifying problems, and supplementing the management system.

Impact of Media Coverage on Influenza Vaccine Coverage in Elderly Individuals from 2020 to 2021 in the Republic of Korea.

Increased awareness of adverse events following immunization (AEFI) can disrupt vaccination programs. In South Korea, a report of alleged influenza vaccine-related deaths attracted significant media attention in 2020. We retrieved the vaccination coverage and AEFI data to determine their association with media coverage. Between 2015 and 2019, the vaccination coverage rate ranged between 80.5% and 83.3%; however, the vaccination coverage rate declined significantly from 2020 to 2021 to 73.6% (p < 0.0001). During the 43rd week of 2020, following a large amount of media coverage on vaccine safety issues, the number of cases with AEFI reached 60. Between 2015 and 2020, the mortality rate ratios for influenza vaccines and non-vaccines ranged between 0.1296 (95% confidence interval (CI), 0.1262-0.1331, p < 0.0001) and 0.1608 (95% CI, 0.1572-0.1644, p < 0.0001). Vaccine safety surveillance should be continued in conjunction with investigation and transparent risk communication to maintain public trust in vaccines and vaccinations.

Association of Early Menarche with Adolescent Health in the Setting of Rapidly Decreasing Age at Menarche.

STUDY OBJECTIVE: This study aimed to investigate the association between age at menarche (AAM) and adverse health indicators in adolescent girls. DESIGN: A retrospective cohort study. SETTING: Population-based survey data. PARTICIPANTS: A total of 319,437 female participants aged 12-18 years from the Korea Youth Risk Behaviour Web-based Survey. INTERVENTIONS AND MAIN OUTCOME MEASURES: We assessed associations between AAM (categorized as ≤10, 11, and ≥12) and health indicators (poor self-rated health, high psychological stress, unhappiness, sexual initiation, and pregnancy). Covariates were individual-level (bodyweight, living with family, parent's education, household wealth, and presence of parents and siblings) and community-level factors (year of birth, single-sex education and level of school, urbanization level of school area, year of survey, and regional deprivation). Odds ratios (ORs) for each adverse health indicator were examined by each AAM group using multivariable regression analyses. For pregnancy, we calculated relative risks (RRs) using a log-binomial regression model. RESULTS: Age at menarche was <12 in 42% of our study population. Nearly one-half of the girls born in the early 2000s went through menarche before the age of 12 years, whereas only one-third of girls born in the early 1990s went through menarche before the age of 12 years. Girls who experienced menarche at age ≤10 or age 11 years were more likely to show self-rated poor health (AAM ≤ 10: OR, 1.28; 95% confidence intervals [CI], 1.22-1.34; AAM = 11: OR, 1.16; 95% CI, 1.12-1.21), high stress (OR, 1.19; 95% CI, 1.14-1.23, and OR, 1.10; 95% CI, 1.06-1.14), and sexual initiation (OR, 2.21; 95% CI, 2.05-2.38, and OR, 1.32; 95% CI, 1.23-1.41) compared to those with AAM ≥12 years when data were adjusted for all covariates. AAM ≤10 years was associated with consistently higher odds for poor health than AAM ≥12 years. The ORs of sexual initiation increased with earlier AAM. Risk of pregnancy was similar across AAM groups when individual- and community-level covariates were controlled for. CONCLUSION: Early menarche, defined as <12 years, can be still a useful indicator in adolescent health interventions to identify high-risk groups in the setting of declining AAM.

Cost-effectiveness of influenza vaccine strategies for the elderly in South Korea.

OBJECTIVES: Despite a high vaccine uptake rate of over 80% in South Korea, the disease burden of influenza is still high among the elderly, which may be due to low effectiveness of vaccines. Therefore, the cost-effectiveness of use among the elderly was analyzed in order to compare the current trivalent influenza vaccine (TIV) with a quadrivalent influenza vaccine (QIV) or MF59-adjuvanted trivalent influenza vaccine (ATIV). METHODS: A static lifetime Markov model was used. It was assumed that the model would be repeated until individuals reached the age of 100. Cost-effectiveness was analyzed across three age groups (65-74 years, 75-84 years, and ≥85 years), and the at-risk group was studied. RESULTS: Compared to the TIV, the QIV was expected to reduce the number of influenza infections by 342,873, complications by 17,011, hospitalizations by 8,568, and deaths by 2,031. The QIV was highly cost-effective when compared to the TIV, with a base case incremental cost-effectiveness ratio (ICER) estimated at USD 17,699/QALY (1USD = 1,151KRW), and the ICER decreased with age and was USD 3,431/QALY in the group aged 85 and above. Sensitivity analysis revealed that the ICER was sensitive to the QIV price, the proportion of influenza B, and vaccine mismatching. On the other hand, the ATIV was expected to reduce the number of influenza cases and complications by 1,812,395 and 89,747, respectively, annually, yielding cost-saving among all ages. ATIV price and vaccine efficacy were the most influential parameters for the ICER of ATIV. CONCLUSIONS: The QIV and ATIV strategies were considered more cost-effective in comparison to the TIV for vaccination strategies implemented for the elderly. However, owing to a lack of data on the effectiveness of ATIV among the elderly, a large-scale effectiveness study is required.

Clinical Application of Targeted Deep Sequencing in Solid-Cancer Patients and Utility for Biomarker-Selected Clinical Trials.

Molecular profiling of actionable mutations in refractory cancer patients has the potential to enable "precision medicine," wherein individualized therapies are guided based on genomic profiling. The molecular-screening program was intended to route participants to different candidate drugs in trials based on clinical-sequencing reports. In this screening program, we used a custom target-enrichment panel consisting of cancer-related genes to interrogate single-nucleotide variants, insertions and deletions, copy number variants, and a subset of gene fusions. From August 2014 through April 2015, 654 patients consented to participate in the program at Samsung Medical Center. Of these patients, 588 passed the quality control process for the 381-gene cancer-panel test, and 418 patients were included in the final analysis as being eligible for any anticancer treatment (127 gastric cancer, 122 colorectal cancer, 62 pancreatic/biliary tract cancer, 67 sarcoma/other cancer, and 40 genitourinary cancer patients). Of the 418 patients, 55 (12%) harbored a biomarker that guided them to a biomarker-selected clinical trial, and 184 (44%) patients harbored at least one genomic alteration that was potentially targetable. This study demonstrated that the panel-based sequencing program resulted in an increased rate of trial enrollment of metastatic cancer patients into biomarker-selected clinical trials. Given the expanding list of biomarker-selected trials, the guidance percentage to matched trials is anticipated to increase. IMPLICATIONS FOR PRACTICE: This study demonstrated that the panel-based sequencing program resulted in an increased rate of trial enrollment of metastatic cancer patients into biomarker-selected clinical trials. Given the expanding list of biomarker-selected trials, the guidance percentage to matched trials is anticipated to increase.

Forecasting Cause-Specific Mortality in Korea up to Year 2032.

Forecasting cause-specific mortality can help estimate the future burden of diseases and provide a clue for preventing diseases. Our objective was to forecast the mortality for causes of death in the future (2013-2032) based on the past trends (1983-2012) in Korea. The death data consisted of 12 major causes of death from 1983 to 2012 and the population data consisted of the observed and estimated populations (1983-2032) in Korea. The modified age-period-cohort model with an R-based program, nordpred software, was used to forecast future mortality. Although the age-standardized rates for the world standard population for both sexes are expected to decrease from 2008-2012 to 2028-2032 (males: -31.4%, females: -32.3%), the crude rates are expected to increase (males: 46.3%, females: 33.4%). The total number of deaths is also estimated to increase (males: 52.7%, females: 41.9%). Additionally, the largest contribution to the overall change in deaths was the change in the age structures. Several causes of death are projected to increase in both sexes (cancer, suicide, heart diseases, pneumonia and Alzheimer's disease), while others are projected to decrease (cerebrovascular diseases, liver diseases, diabetes mellitus, traffic accidents, chronic lower respiratory diseases, and pulmonary tuberculosis). Cancer is expected to be the highest cause of death for both the 2008-2012 and 2028-2032 time periods in Korea. To reduce the disease burden, projections of the future cause-specific mortality should be used as fundamental data for developing public health policies.

Cancer Mortality Projections in Korea up to 2032.

Predicting cancer mortality is important to estimate the needs of cancer-related services and to prevent cancer. Despite its significance, a long-term future projection of cancer mortality has not been conducted; therefore, our objective was to estimate future cancer mortality in Korea by cancer site through 2032. The specially designed Nordpred software was used to estimate cancer mortality. The cancer death data from 1983 to 2012 and the population projection data from 1983 to 2032 were obtained from the Korean National Statistics Office. Based on our analysis, age-standardized rates with the world standard population of all cancer deaths were estimated to decline from 2008-2012 to 2028-2032 (men: -39.8%, women: -33.1%). However, the crude rates are predicted to rise (men: 29.8%, women: 24.4%), and the overall number of the cancer deaths is also estimated to increase (men: 35.5%, women: 32.3%). Several cancer deaths are projected to increase (lung, liver and gallbladder, colon and rectum, pancreas and leukemia in both sexes; prostate cancer in men; and breast and ovarian cancer in women), whereas other cancer deaths are expected to decrease (stomach, esophagus and larynx in both sexes and cervical cancer in women). The largest contribution to increasing cancer deaths is due to the aging of the Korean population. In conclusion, a strategy for primary prevention, early detection, and early treatment to cope with the rapidly increasing death of cancer due to population aging is urgently required.

Regional Deprivation Index and Socioeconomic Inequalities Related to Infant Deaths in Korea.

Deprivation indices have been widely used to evaluate neighborhood socioeconomic status and therefore examine individuals within their regional context. Although some studies on the development of deprivation indices were conducted in Korea, additional research is needed to construct a more valid and reliable deprivation index. Therefore, a new deprivation index, named the K index, was constructed using principal component analysis. This index was compared with the Carstairs, Townsend and Choi indices. A possible association between infant death and deprivation was explored using the K index. The K index had a higher correlation with the infant mortality rate than did the other three indices. The regional deprivation quintiles were unequally distributed throughout the country. Despite the overall trend of gradually decreasing infant mortality rates, inequalities in infant deaths according to the deprivation quintiles persisted and widened. Despite its significance, the regional deprivation variable had a smaller effect on infant deaths than did individual variables. The K index functions as a deprivation index, and we may use this index to estimate the regional socioeconomic status in Korea. We found that inequalities in infant deaths according to the time trend persisted. To reduce the health inequalities among infants in Korea, regional deprivation should be considered.

Effects of the temporary placement of a self-expandable metallic stent in benign pyloric stenosis.

BACKGROUND/AIMS: The use of self-expandable metallic stents (SEMS) is an established palliative treatment for malignant stenosis in the gastrointestinal tract; therefore, its application to benign stenosis is expected to be beneficial because of the more gradual and sustained dilatation in the stenotic portion. We aimed in this prospective observational study to evaluate the efficacy and safety of temporary SEMS placement in benign pyloric stenosis. METHODS: Twenty-two patients with benign stenosis of the prepylorus, pylorus, and duodenal bulb were enrolled and underwent SEMS placement. We assessed symptom improvement, defined as an increase of at least 1 degree in the gastric-outlet-obstruction scoring system after stent insertion. RESULTS: No major complications were observed during the procedures. After stent placement, early symptom improvement was achieved in 18 of 22 patients (81.8%). During the follow-up period (mean 10.2 months), the stents remained in place successfully for 6 to 8 weeks in seven patients (31.8%). Among the 15 patients (62.5%) with stent migration, seven (46.6%) showed continued symptomatic improvement without recurrence of obstructive symptoms. CONCLUSIONS: Despite the symptomatic improvement, temporary SEMS placement is premature as an effective therapeutic tool for benign pyloric stenosis unless a novel stent is developed to prevent migration.

Prevalence and endoscopic features of eosinophilic esophagitis in patients with esophageal or upper gastrointestinal symptoms.

OBJECTIVE: This study was aimed to evaluate the prevalence of eosinophilic esophagitis (EoE) among patients with esophageal or upper gastrointestinal (UGI) symptoms. METHODS: Patients with esophageal or UGI symptoms including dysphagia food impaction, acid regurgitation, heartburn, chest pain, epigastric pain, nausea and/or vomiting were prospectively collected. The enrolled patients responded to a symptomatic questionnaire and underwent an esophagogastroduodenoscopy and esophageal biopsies. Supportive endoscopic findings of EoE (ring-like appearance, liner furrows, whitish papules, shearing or friability) were recorded. EoE was diagnosed if patients had chronic UGI or esophageal symptoms, the esophageal biopsy showed ≥15 eosinophils/high-power field and were unresponsive to 2-3 weeks of proton pump inhibitors. RESULTS: A total of 122 patients were enrolled and supportive endoscopic findings were found in 31 (25.4%) patients [whitish papules: 19 (15.6%), ring-like appearance: 8 (6.6%), linear furrows: 5 (4.1%)]. One patient had a simultaneous ring-like appearance and linear furrows. EoE was diagnosed in 8 (6.6%) patients and supportive endoscopic findings and past history of gastroesophageal reflux disease, allergic rhinitis and atopic dermatitis were more common in EoE positive than EoE negative patients. The diagnostic yield of endoscopic findings was 40.0% (2/5) in linear furrows, 25.0% (2/8) in ring-like appearance and 15.8% (3/19) in whitish papules. CONCLUSION: Prevalence of EoE among patients with esophageal or UGI symptoms was 6.6%. Linear furrows and ring-like appearance had a relatively high diagnostic value.

[Clinicopathologic characteristics of patients who underwent curative additional gastrectomy after endoscopic submucosal dissection for early gastric cancer or adenoma].

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) has been widely performed. However, procedure related-complications and the risk of tumor recurrence are limitations. We analyzed the clinicopathological characteristics of patients who underwent curative additional gastrectomy (gastrectomy) after ESD. METHODS: The clinical characteristics of cases underwent gastrectomy after ESD were retrospectively analyzed. RESULTS: Between January 2002 and August 2010, 1,512 cases underwent ESD for early gastric cancer (n=511) or adenoma (n=1,001). Thirty-two cases (2.1%) underwent gastrectomy after ESD. Thirty cases (2.0%) were EGC and 2 cases (0.1%) were adenoma. Extended indication, larger tumor size and piecemeal resection were risk factors for gastrectomy after ESD. According to the causes of gastrectomy, 13 cases underwent gastrectomy due to complications (40.6%; bleeding in 9, perforation in 4), and 19 cases based on pathological results (incomplete resection in 13, lymphatic invasion in 6). In cases with incomplete resection, the rate of residual tumor and lymph node metastasis after gastrectomy was 69.2% (75% lateral margin, 60% deep and 75% both) and 7.7%, respectively. Three (50%) of the 6 cases with lymphatic invasion had lymph node metatstasis. CONCLUSIONS: The causes of gastrectomy after ESD were the procedure-related complications, the incomplete resection and lymphatic invasion. For complete and curative ESD, endoscopists should try to minimize complications and determine the depth of invasion accurately before ESD.

[Clinicopathologic features of cases with negative pathologic results after endoscopic submucosal dissection].

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) is accepted as a standard treatment of early gastric cancer (EGC) and gastric adenoma. Occasionally, tumorous lesion is not found and pathologic discrepancies can occur after ESD. The aim of this study was to analyze the factors affecting the negative pathologic results after ESD. METHODS: We retrospectively reviewed the data from all patients with gastric neoplasm (276 EGC and 516 gastric adenomas) who were treated with ESD during past 3 years and enrolled the patients who had negative pathologic results. RESULTS: Out of 792 patients treated with ESD, 27 patients (3.4%) were eligible for inclusion. Among the 27 patients, factors affecting the negative pathologic results were, most commonly, the focal lesion (n=13, 48.2%) which was small enough to be removed completely during pre-ESD biopsy, followed by pathologic discrepancies (n=11, 40.7%) between pathologists and lastly the operator factor (n=3, 11.1%) dissecting incorrect lesions. Of the focal lesions, the initial pathologic diagnoses were adenocarcinoma in 11 cases (84.6%). In cases with pathologic discrepancies, all the pretreatment diagnoses were adenoma with low grade dysplasia. In cases caused by operator factors, intestinal metaplasia was accompanied by elevated adenoma in all cases. CONCLUSIONS: To decrease negative pathologic results after ESD, an endoscopist should perform ESD after sufficient communication with pathologists, especially for adenoma with low grade dysplasia, and choose correct lesion, especially located at the antrum and associated with intestinal metaplasia. The possibility of total removal of small lesions even by forcep biopsy should be considered.