BACKGROUND: Although there are controversies regarding the benefit of fluoropyrimidine-based adjuvant chemotherapy in patients with microsatellite instability-high (MSI-H) colorectal cancer (CRC), the pathologic features affecting postchemotherapeutic prognosis in these patients have not been fully identified yet. METHODS: A total of 26 histopathologic and immunohistochemical factors were comprehensively evaluated in 125 stage II or III MSI-H CRC patients who underwent curative resection followed by fluoropyrimidine-based adjuvant chemotherapy. We statistically analyzed the associations of these factors with disease-free survival (DFS). RESULTS: Using a Kaplan- Meier analysis with log-rank test, we determined that ulceroinfiltrative gross type (p=.003), pT4 (p<.001), pN2 (p=.002), perineural invasion (p=.001), absence of peritumoral lymphoid reaction (p=.041), signet ring cell component (p=.006), and cribriform comedo component (p=.004) were significantly associated with worse DFS in patients receiving oxaliplatin-based adjuvant chemotherapy (n=45). By contrast, pT4 (p<.001) and tumor budding-positivity (p=.032) were significant predictors of poor survival in patients receiving non-oxaliplatin-based adjuvant chemotherapy (n=80). In Cox proportional hazards regression model-based univariate and multivariate analyses, pT category (pT1-3 vs pT4) was the only significant prognostic factor in patients receiving non-oxaliplatin-based adjuvant chemotherapy, whereas pT category, signet ring cell histology and cribriform comedo histology remained independent prognostic factors in patients receiving oxaliplatin-based adjuvant chemotherapy. CONCLUSIONS: pT4 status is the most significant pathologic determinant of poor outcome after fluoropyrimidine-based adjuvant chemotherapy in patients with stage II/III MSI-H CRC.
Cellular Structures ; Chemotherapy, Adjuvant* ; Colorectal Neoplasms* ; Disease-Free Survival ; Humans ; Microsatellite Instability ; Microsatellite Repeats ; Multivariate Analysis ; Pathology ; Prognosis*

BACKGROUND: There is a recent trend of increased use of the gel test for the detection of unexpected antibodies (Abs) because of its simplicity and ease with which definitive interpretation can be made. However, because of the low insurance payments in Korea, only the LISS/Coombs card is used and thus the detection rate of the cold Abs has decreased. We have studied the detection rates of the Abs in patients by using the LISS/Coombs gel test and thus evaluated the clinical usefulness of the LISS/Coombs gel test. METHODS: Abs screening tests have been carried out using the DiaMed(TM) LISS/Coombs gel card test (Murten, Switzerland) on 14,942 patients for whom blood transfusions were ordered between July 1, 1997 and March 31, 2001. When the test for Abs was positive, Ab identification tests were further carried out with the DiaMed(TM) LISS/Coombs gel card and the ID-DiaPanel 1-11. RESULTS: Eighty-one out of 14,942 patients (0.54%) revealed positive results. Of these, 15 showed anti-E, 5 showed anti-E+c, 4 showed anti-C, 3 showed anti-D, 2 showed anti-Jk(a), 1 each showed anti-c, anti-M, anti-Lu(a), and anti-K Abs. CONCLUSIONS: Although the detection rate for the cold Abs of the LISS/Coombs gel test was low, it is considered to be highly useful because of the high detection rate for the clinically important warm Abs, the simplicity in carrying out the test, and the easy readability of test results.
Antibodies ; Blood Transfusion ; Comprehension ; Humans ; Insurance ; Korea ; Mass Screening

BACKGROUND: A receptor tyrosine kinase for ephrin ligands, EPHB2, is expressed in normal colorectal tissues and colorectal cancers (CRCs). The aim of this study was to investigate EPHB2 expression over CRC progression and determine its prognostic significance in CRC. METHODS: To measure EPHB2 mRNA and protein expression, real-time polymerase chain reaction and immunohistochemistry were performed in 32 fresh-frozen and 567 formalin-fixed paraffin-embedded CRC samples, respectively. We further investigated clinicopathological features and overall and recurrence-free survival according to EPHB2 protein expression. RESULTS: The EPHB2 level was upregulated in CRC samples compared to non-cancerous tissue in most samples and showed a strong positive correlation with AXIN2. Notably, CD44 had a positive association with both mRNA and protein levels of EPHB2. Immunohistochemical analysis revealed no difference in EPHB2 expression between adenoma and carcinoma areas. Although EPHB2 expression was slightly lower in invasive fronts compared to surface area (p < .05), there was no difference between superficial and metastatic areas. EPHB2 positivity was associated with lymphatic (p < .001) and venous (p = .001) invasion, TNM stage (p < .001), and microsatellite instability (p = .036). Kaplan–Meier analysis demonstrated that CRC patients with EPHB2 positivity showed better clinical outcomes in both overall (p = .049) and recurrence-free survival (p = .015). However, multivariate analysis failed to show that EPHB2 is an independent prognostic marker in CRCs (hazard ratio, 0.692; p = .692). CONCLUSIONS: Our results suggest that EPHB2 is overexpressed in a subset of CRCs and is a significant prognostic marker.
Adenoma ; Colorectal Neoplasms ; Humans ; Immunohistochemistry ; Ligands ; Microsatellite Instability ; Multivariate Analysis ; Prognosis ; Protein-Tyrosine Kinases ; Real-Time Polymerase Chain Reaction ; Receptor, EphB2 ; RNA, Messenger

OBJECTIVES: The present study aimed to evaluate the validity of a set of self-reported questionnaires for periodontitis for estimating the prevalence of chronic adult periodontitis in the Korean population. METHODS: The questionnaire is comprised of a total of 14 questions with four summarized concepts including self-diagnosis of oral status, subjective signs related to oral health, smoking and drinking status, and use of auxiliary oral hygiene devices including scaling. The predictiveness of the measures from these self-reported questions was assessed by logistic regression modeling using receiver operating characteristic (ROC) statistics, sensitivity, and specificity. RESULTS: The sensitivity, specificity, and AUC including all questions were 0.571, 0.768, and 0.781, respectively; the sum of sensitivity and specificity was 1.34. To gain robustness, a simplified predictive model was built with six questions. Its results were 0.536, 0.817, and 0.762 for sensitivity, specificity, and AUC, respectively. The sum of sensitivity and specificity was found to be 1.35. CONCLUSIONS: The self-reported questionnaire for periodontitis showed considerable validity, but further study is required to provide optimal validity and predictability.
Area Under Curve ; Chronic Periodontitis ; Drinking ; Logistic Models ; Oral Health ; Oral Hygiene ; Periodontal Diseases ; Periodontitis* ; Prevalence ; Surveys and Questionnaires* ; ROC Curve ; Sensitivity and Specificity ; Smoke ; Smoking

Background: This study aimed to determine the effect of ramen sauce on tooth tone changes over time, after selecting three different ramen colors from the ramens sold in the market, and applying the sauce to bovine teeth. Methods: Healthy bovine teeth were selected, and cutting discs were used to produce 60 specimens (5×5×3 mm), with 15 specimens distributed per county. Three types of ramen (buldak, chacharoni black bean sauce, and ottogi curry noodle) were used as the experimental group, and water was used as the negative control group. Tooth tone measurement was performed using a spectrophotometer (CM-700d) to measure the color before and after 1 (3 h 44 min), 2 (7 h 28 min), 3 (11 h 12 min), and 4 weeks (14 h 56 min). Analysis of the color tone change was performed using Statistical Package for the Social Sciences version 28. Results: In the experimental group, there was a significant color tone change before and after immersion. L* indicated the largest change in black bean sauce ramen, a* indicated buldak ramen, and b* indicated the largest change in curry ramen. The amount of color change (ΔE*) was the largest in curry ramen, followed by buldak and black bean sauce ramens. The results of the post-hoc analysis showed significant differences between all groups except buldak and black bean sauce ramens. Conclusion All three types of ramen revealed significant color change before and after immersion, and curry ramen showed the largest amount of color change among them.

BACKGROUND: Recent studies have revealed that a small subset of Lynch syndrome-associated colorectal carcinomas (CRCs) is caused by a germline EPCAM deletion-induced MSH2 epimutation. Based on the finding of this genetic alteration, we investigated the implications of EPCAM expression changes in microsatellite instability-high (MSI-H) CRCs. METHODS: Expression of EPCAM and DNA mismatch repair proteins was assessed by immunohistochemistry in 168 MSI-H CRCs. Using DNA samples of these tumors, MLH1 promoter methylation status was also determined by methylation-specific real-time polymerase chain reaction method (MethyLight). RESULTS: Among 168 MSI-H CRCs, complete loss (CL) and focal loss (FL) of EPCAM expression was observed in two (1.2%) and 22 (13.1%) cases, respectively. Both of the EPCAM-CL cases were found in MSH2-negative tumors without MLH1 promoter methylation. However, only nine of the 22 EPCAM-FL tumors had MSH2 deficiency. Of the 22 EPCAM-FL tumors, 13 showed MLH1 loss, and among them, nine cases were determined to have MLH1 methylation. EPCAM-FL was significantly associated with advanced stage (p=.043), distant metastasis (p=.003), poor differentiation (p=.001), and signet ring cell component (p=.004). CONCLUSIONS: Loss of EPCAM expression is differentially associated with clinicopathological and molecular features, depending on the completeness of the loss, in MSI-H CRCs.
Cellular Structures ; Colorectal Neoplasms* ; DNA ; DNA Mismatch Repair ; Immunohistochemistry ; Methylation ; Microsatellite Instability ; Microsatellite Repeats ; Neoplasm Metastasis ; Real-Time Polymerase Chain Reaction

OBJECTIVES: This pilot study aimed to evaluate the effect of dental amalgam, a restorative material, on children by measuring the mercury concentration in the urine as well as the number of teeth filled with dental amalgam. METHODS: Twenty children enrolled in grades 1-4 of two elementary schools in Daegu participated in this study. One trained dentist performed oral examinations and removed amalgam restorations from the teeth with a high and low speed handpiece. In order to measure the urinary mercury concentrations, urine samples were collected from all participants at baseline and immediately and 24 hours after removal of the dental amalgam restorations. RESULTS: The mean number of teeth from which the amalgam restorations was removed was 9.8 while the mean urinary mercury concentrations at baseline, immediately, and 24 hours after removal of dental amalgam restorations were 2.66, 2.76, and 2.76 microg/g creatinine, respectively. The mean urinary mercury concentration increased consistently after amalgam restoration removal. For those participants whose removed amalgamated surfaces were more than 11, the mean urinary mercury concentration immediately after amalgam restoration removal and 24 hours after removal increased consistently but showed no significant difference. CONCLUSIONS: This study demonstrated that dental amalgam restoration was related to urinary mercury concentration, and these findings present a possibility of mercury accumulation in the body. Therefore, we suggest future longitudinal studies to ensure the safety of children exposed to mercury by establishing criteria for amalgam removal.
Child* ; Creatinine ; Daegu ; Dental Amalgam ; Dentists ; Diagnosis, Oral ; Humans ; Longitudinal Studies ; Pilot Projects* ; Tooth

BACKGROUND/OBJECTIVES: Inflammatory Bowel Disease (IBD) has rapidly escalated in Asia (including Korea) due to increasing westernized diet patterns subsequent to industrialization. Factors associated with endoplasmic reticulum (ER) stress are demonstrated to be one of the major causes of IBD. This study was conducted to investigate the effect of Lycium barbarum (L. barbarum) on ER stress. MATERIALS/METHODS: Mouse embryonic fibroblast (MEF) cell line and polarized Caco-2 human intestinal epithelial cells were treated with crude extract of the L. chinense fruit (LF). Paracellular permeability was measured to examine the effect of tight junction (TJ) integrity. The regulatory pathways of ER stress were evaluated in MEF knockout (KO) cell lines by qPCR for interleukin (IL) 6, IL8 and XBP1 spliced form (XBP1s). Immunoglobulin binding protein (BiP), XBP1s and CCAAT/enhancer-binding homologous protein (CHOP) expressions were measured by RT-PCR. Scanning Ion Conductance Microscopy (SICM) at high resolution was applied to observe morphological changes after treatments. RESULTS: Exposure to LF extract strengthened the TJ, both in the presence and absence of inflammation. In polarized Caco-2 pretreated with LF, induction in the expression of proinflammatory marker IL8 was not significant, whereas ER stress marker XBP1s expression was significantly increased. In wild type (wt) MEF cells, IL6, CHOP and XBP1 spliced form were dose-dependently induced when exposed to 12.5–50 µg/mL extract. However, absence of XBP1 or IRE1α in MEF cells abolished this effect. CONCLUSION: Results of this study show that LF treatment enhances the barrier function and reduces inflammation and ER stress in an IRE1α-XBP1-dependent manner. These results suggest the preventive effect of LF on healthy intestine, and the possibility of reducing the degree of inflammatory symptoms in IBD patients.
Animals ; Asia ; Carrier Proteins ; Cell Line ; Diet ; Endoplasmic Reticulum ; Epithelial Cells ; Fibroblasts ; Fruit ; Humans ; Immunoglobulins ; Inflammation ; Inflammatory Bowel Diseases ; Interleukin-6 ; Interleukin-8 ; Interleukins ; Intestines ; Lycium ; Mice ; Microscopy ; Permeability ; Tight Junctions

BACKGROUND: Previous studies on synchronous colorectal carcinoma (SCRC) have reported inconsistent results about its clinicopathologic and molecular features and prognostic significance. METHODS: Forty-six patients with multiple advanced tumors (T2 or higher category) who did not receive neoadjuvant chemotherapy and/or radiotherapy and who are not associated with familial adenomatous polyposis were selected and 99 tumors from them were subjected to clinicopathologic and molecular analysis. Ninety-two cases of solitary colorectal carcinoma (CRC) were selected as a control considering the distributions of types of surgeries performed on patients with SCRC and T categories of individual tumors from SCRC. RESULTS: SCRC with multiple advanced tumors was significantly associated with more frequent nodal metastasis (p = .003) and distant metastasis (p = .001) than solitary CRC. KRAS mutation, microsatellite instability, and CpG island methylator phenotype statuses were not different between SCRC and solitary CRC groups. In univariate survival analysis, overall and recurrence-free survival were significantly lower in patients with SCRC than in patients with solitary CRC, even after adjusting for the extensiveness of surgical procedure, adjuvant chemotherapy, or staging. Multivariate Cox regression analysis revealed that tumor multiplicity was an independent prognostic factor for overall survival (hazard ratio, 4.618; 95% confidence interval, 2.126 to 10.030; p < .001), but not for recurrence-free survival (p = .151). CONCLUSIONS: Findings suggested that multiplicity of advanced T category–tumors might be associated with an increased risk of nodal metastasis and a risk factor for poor survival, which raises a concern about the guideline of American Joint Committee on Cancer's tumor-node-metastasis staging that T staging of an index tumor determines T staging of SCRC.
Adenomatous Polyposis Coli ; Chemotherapy, Adjuvant ; Colorectal Neoplasms ; CpG Islands ; Drug Therapy ; Humans ; Joints ; Microsatellite Instability ; Neoplasm Metastasis ; Phenotype ; Radiotherapy ; Risk Factors

Purpose: The purpose of this study was to reveal the clinicopathological characteristics and prognostic implications associated with fibroblast growth factor receptor 1 (FGFR1) amplification in colorectal cancers (CRCs). Materials and Methods: We measured the copy number of FGFR1 by droplet digital polymerase chain reaction (ddPCR), and analyzed the FGFR1 expression by immunohistochemistry, in 764 surgically resected CRCs (SNUH2007 dataset, 384 CRCs; SNUH Folfox dataset, 380 CRCs). Results: CRCs with ≥ 3.3 copies of the FGFR1 gene were classified as FGFR1 amplified. FGFR1 amplification was found in 10 of the 384 CRCs (2.6%) in the SNUH2007 dataset, and in 28 of the 380 CRCs (7.4%) in the SNUH Folfox dataset. In the SNUH2007 dataset, there was no association between the FGFR1 copy number status and sex, gross appearance, stage, or differentiation. High FGFR1 expression was associated with female sex and KRAS mutation. At the molecular level, FGFR1 amplification was mutually exclusive with BRAF mutation, microsatellite instability, and MLH1 methylation, in both SNUH2007 and SNUH Folfox datasets. Survival analysis revealed that FGFR1 amplification was associated with significantly worse clinical outcome compared with no FGFR1 amplification, in both SNUH2007 and SNUH Folfox datasets. Within the SNUH2007 dataset, CRC patients with high FGFR1 expression had an inferior progression-free survival compared with those with low FGFR1 expression. The FGFR inhibitor, PD173074, repressed the proliferation of a CRC cell line overexpressing FGFR1, but not of cells with FGFR1 amplification. Conclusion FGFR1 amplification measured by ddPCR can be a prognostic indicator of poor clinical outcome in patients with CRCs.