Melanogenesis is the production of melanin from tyrosine by a series of enzyme-catalyzed reactions, in which tyrosinase and DOPA oxidase play key roles. The melanin content in the skin determines skin pigmentation. Abnormalities in skin pigmentation lead to various skin pigmentation disorders. Recent research has shown that the expression of EMP2 is much lower in melanoma than in normal melanocytes, but its role in melanogenesis has not yet been elucidated. Therefore, we investigated the role of EMP2 in the melanogenesis of MNT1 human melanoma cells. We examined TRP-1, TRP-2, and TYR expression levels during melanogenesis in MNT1 melanoma cells by gene silencing of EMP2. Western blot and RT-PCR results confirmed that the expression levels of TYR and TRP-2 were decreased when EMP2 expression was knocked down by EMP2 siRNA in MNT1 cells, and these changes were reversed when EMP2 was overexpressed. We verified the EMP2 gene was knocked out of the cell line (EMP2 CRISPR/Cas9) by using a CRISPR/Cas9 system and found that the expression levels of TRP-2 and TYR were significantly lower in the EMP2 CRISPR/Cas9 cell lines. Loss of EMP2 also reduced migration and invasion of MNT1 melanoma cells. In addition, the melanosome transfer from the melanocytes to keratinocytes in the EMP2 KO cells cocultured with keratinocytes was reduced compared to the cells in the control coculture group. In conclusion, these results suggest that EMP2 is involved in melanogenesis via the regulation of TRP-2 expression.

Background/Aims: Several prediction models for evaluating the prognosis of nonmetastatic resected pancreatic ductal adenocarcinoma (PDAC) have been developed, and their performances were reported to be superior to that of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. We developed a prediction model to evaluate the prognosis of resected PDAC and externally validated it with data from a nationwide Korean database. Methods: Data from the Surveillance, Epidemiology and End Results (SEER) database were utilized for model development, and data from the Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP) database were used for external validation. Potential candidate variables for model development were age, sex, histologic differentiation, tumor location, adjuvant chemotherapy, and the AJCC 8th staging system T and N stages. For external validation, the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (AUC) were evaluated. Results: Between 2004 and 2016, data from 9,624 patients were utilized for model development, and data from 3,282 patients were used for external validation. In the multivariate Cox proportional hazard model, age, sex, tumor location, T and N stages, histologic differentiation, and adjuvant chemotherapy were independent prognostic factors for resected PDAC. After an exhaustive search and 10-fold cross validation, the best model was finally developed, which included all prognostic variables. The C-index, 1-year, 2-year, 3-year, and 5-year time-dependent AUCs were 0.628, 0.650, 0.665, 0.675, and 0.686, respectively. Conclusions The survival prediction model for resected PDAC could provide quantitative survival probabilities with reliable performance. External validation studies with other nationwide databases are needed to evaluate the performance of this model.

Purpose: To analyze topographic progression of geographic atrophy with different concentric circles centered on the fovea in correlation with decrease of visual acuity. Methods: We retrospectively analyzed 36 eyes of 26 patients diagnosed with geographic atrophy and followed at least 1 year. One millimeter circular area at the foveal center were defined as zone 1, and doughnut shape areas from between 1 and 2 mm to between 5 and 6 mm were defined as zone 2 to 6. Then, changes of geographic atrophy area in each zone were measured with semi-automatic software. Correlation analysis and regression analysis were performed to determine the relationship between changes in visual acuity and atrophic area in each zone. Results: Mean age was 76.9 years and follow-up period were 3.38 years. The mean atrophic area increased from 8.09 to 16.34 mm2 and visual acuity decreased from 0.39 to 0.69 on logarithm of the minimal angle of resolution. Mean change of total geographic atrophy area was not significantly correlated with visual acuity decrease. While geographic atrophy progression within zone 1, 2, and 3 showed significant causal relationship with decrease of visual acuity (all, p < 0.05). Conclusions In contrast to the total geographic atrophy area, progression of geographic atrophy in parafoveal area was significantly correlated with decrease of visual acuity.

Background: Since September 2015, the initiation of antiviral therapy (AVT) for patients with chronic hepatitis B (CHB)-related cirrhosis has been reimbursed according to the revised Korean Association for the Study of Liver (KASL) guideline, if the patient had hepatitis B virus DNA level ≥ 2,000 IU/L, regardless of aminotransferase or alanine aminotransferase levels. This study investigated whether the KASL guideline implementation reduced the risk of CHB-related hepatocellular carcinoma (HCC) in patients with cirrhosis in South Korea. Methods: A total of 429 patients with CHB-related cirrhosis who initiated AVT between 2014 and 2016 were recruited. The risk of HCC development was compared between patients who initiated AVT before and after September 2015 (pre-guideline [n = 196, 45.7%] vs. postguideline implementation [n = 233, 54.3%]). Results: Univariate analysis showed that AVT initiation before guideline implementation, older age, male gender, and diabetes significantly predicted increased risk of HCC development (all P < 0.05). Subsequent multivariate analysis showed that AVT initiation before guideline implementation (HR = 1.941), older age (HR = 5.762), male gender (HR = 2.555), and diabetes (HR = 1.568) independently predicted increased risk of HCC development (all P < 0.05). Additionally, multivariate analysis showed that AVT initiation before guideline implementation (HR = 2.309), male gender (HR = 3.058), and lower platelet count (HR = 0.989) independently predicted mortality (P < 0.05). The cumulative incidences of HCC and mortality were significantly higher in patients who initiated AVT before guideline implementation than in those who initiated AVT after guideline implementation (all P < 0.05, log-rank test). Conclusion The prognosis of patients with CHB-related cirrhosis who initiated AVT improved after guideline implementation according to the revised KASL guideline.

Background: Since September 2015, the initiation of antiviral therapy (AVT) for patients with chronic hepatitis B (CHB)-related cirrhosis has been reimbursed according to the revised Korean Association for the Study of Liver (KASL) guideline, if the patient had hepatitis B virus DNA level ≥ 2,000 IU/L, regardless of aminotransferase or alanine aminotransferase levels. This study investigated whether the KASL guideline implementation reduced the risk of CHB-related hepatocellular carcinoma (HCC) in patients with cirrhosis in South Korea. Methods: A total of 429 patients with CHB-related cirrhosis who initiated AVT between 2014 and 2016 were recruited. The risk of HCC development was compared between patients who initiated AVT before and after September 2015 (pre-guideline [n = 196, 45.7%] vs. postguideline implementation [n = 233, 54.3%]). Results: Univariate analysis showed that AVT initiation before guideline implementation, older age, male gender, and diabetes significantly predicted increased risk of HCC development (all P < 0.05). Subsequent multivariate analysis showed that AVT initiation before guideline implementation (HR = 1.941), older age (HR = 5.762), male gender (HR = 2.555), and diabetes (HR = 1.568) independently predicted increased risk of HCC development (all P < 0.05). Additionally, multivariate analysis showed that AVT initiation before guideline implementation (HR = 2.309), male gender (HR = 3.058), and lower platelet count (HR = 0.989) independently predicted mortality (P < 0.05). The cumulative incidences of HCC and mortality were significantly higher in patients who initiated AVT before guideline implementation than in those who initiated AVT after guideline implementation (all P < 0.05, log-rank test). Conclusion The prognosis of patients with CHB-related cirrhosis who initiated AVT improved after guideline implementation according to the revised KASL guideline.

Background/Aims: Although people with diabetes have been shown to have higher mortality than people without diabetes, there is a lack of data on the association between fasting plasma glucose (FPG) levels and cause-specific mortality rates in the general population. Methods: A total of 326,547 Korean adults over 20 years of age, who had received a health checkup between 2006 and 2008 were selected from the Korean National Health Insurance Service sample cohort dataset and followed until 2015. We estimated hazard ratios (HRs) of all-cause mortality and cause-specific mortality relative to various range of FPG levels. All causes of death were classified according to International Classification of Diseases (ICD)-10 codes. Results: During follow-up (mean, 8.5 years), a total of 13,536 deaths (mortality rate 4.89/1,000 person-year) occurred; 4,916 deaths from cancer, 2,133 from cardiovascular disease, 762 from infectious disease, 199 from renal disease, and 5,526 from other causes. The overall mortality rate increased with an increase in FPG category (HR, 1.78; 95% confidence interval, 1.65 to 1.92; in the ≥ 160 mg/dL). In addition, a J-shaped associations was found between FPG levels and all-cause mortality after adjustment for age, sex, smoking, drinking, physical activity, body mass index, diabetes mellitus medication, hypertension, and dyslipidemia. In particular, the risk of cancer-mortality with high FPG levels was increased for men but not women. Conclusions The risk of all-cause and cause-specific mortality showed the tendency to increase when the FPG level was outside of the normal range, indicating a J-shaped relationship, in both men and women.

Background/Aims: Although people with diabetes have been shown to have higher mortality than people without diabetes, there is a lack of data on the association between fasting plasma glucose (FPG) levels and cause-specific mortality rates in the general population. Methods: A total of 326,547 Korean adults over 20 years of age, who had received a health checkup between 2006 and 2008 were selected from the Korean National Health Insurance Service sample cohort dataset and followed until 2015. We estimated hazard ratios (HRs) of all-cause mortality and cause-specific mortality relative to various range of FPG levels. All causes of death were classified according to International Classification of Diseases (ICD)-10 codes. Results: During follow-up (mean, 8.5 years), a total of 13,536 deaths (mortality rate 4.89/1,000 person-year) occurred; 4,916 deaths from cancer, 2,133 from cardiovascular disease, 762 from infectious disease, 199 from renal disease, and 5,526 from other causes. The overall mortality rate increased with an increase in FPG category (HR, 1.78; 95% confidence interval, 1.65 to 1.92; in the ≥ 160 mg/dL). In addition, a J-shaped associations was found between FPG levels and all-cause mortality after adjustment for age, sex, smoking, drinking, physical activity, body mass index, diabetes mellitus medication, hypertension, and dyslipidemia. In particular, the risk of cancer-mortality with high FPG levels was increased for men but not women. Conclusions The risk of all-cause and cause-specific mortality showed the tendency to increase when the FPG level was outside of the normal range, indicating a J-shaped relationship, in both men and women.

Background/Aims: Prognostic models are lacking for patients with recurrent hepatocellular carcinoma (HCC) following surgical resection. This study devised and validated a new hepatoma arterial-embolization prognostic (HAP) score optimized for use in patients undergoing treatment with transarterial chemoembolization (TACE) for recurrence subsequent to surgical resection of HCC. Methods: Training cohort (n=424) and validation cohort (n=350) patients with recurrent HCC after resection treated with TACE between 2003 and 2016 were enrolled. Cox regression and area under the receiver operating characteristic curve (AUC) analyses were used to identify risk factors for survival and to calculate the predictive performance of risk scores, respectively. Results: The median age of the study population was 59.2 years. α-Fetoprotein >400 ng/mL (hazard ratio [HR]=1.815), serum albumin ≤3.5 g/dL (HR=1.966), tumor number ≥2 (HR=1.425), tumor size >5 cm at resection or recurrence (HR=1.356), segmental portal vein invasion at resection or recurrence (HR=2.032), and time from resection to recurrence ≤1 years (HR=1.849) independently predicted survival (all p<0.05). The postoperative HAP (pHAP) model based on the rounded HRs of these variables showed an AUC of 0.723 for predicting survival at 3 years, which was significantly higher than AUCs of other HAP-based models, including HAP, modified HAP, and modified HAP-II scores (0.578-0.621) (all p<0.05). The accuracy of pHAP was maintained in the entire cohort (n=774; AUC=0.776 at 3 years). Conclusions A new pHAP score optimized for patients treated with TACE due to recurrent HCC after resection showed acceptable accuracy and was externally validated. Further studies of means by which to select treatment options other than TACE for high-risk patients according to pHAP scores are warranted.

The first edition of the ‘Standardized Pathology Report for Colorectal Cancer,’ which was developed by the Gastrointestinal Pathology Study Group (GIP) of the Korean Society of Pathologists, was published 13 years ago. Meanwhile, there have been many changes in the pathologic diagnosis of colorectal cancer (CRC), pathologic findings included in the pathology report, and immunohistochemical and molecular pathology required for the diagnosis and treatment of colorectal cancer. In order to reflect these changes, we (GIP) decided to make the second edition of the report. The purpose of this standardized pathology report is to provide a practical protocol for Korean pathologists, which could help diagnose and treat CRC patients. This report consists of “standard data elements” and “conditional data elements.” Basic pathologic findings and parts necessary for prognostication of CRC patients are classified as “standard data elements,” while other prognostic factors and factors related to adjuvant therapy are classified as “conditional data elements” so that each institution could select the contents according to the characteristics of the institution. The Korean version is also provided separately so that Korean pathologists can easily understand and use this report. We hope that this report will be helpful in the daily practice of CRC diagnosis.

Background and Objectives: The Sapien 3 (S3) valve has not been compared to the Sapien XT (SXT) valve in Korea. We compared procedural and clinical outcomes between the 2 devices. Methods: A total of 189 patients who underwent transcatheter aortic valve replacement (TAVR) with S3 (n=95) or SXT (n=94) valve was analyzed. The primary endpoint was cardiovascular mortality at 1 year. The median follow-up duration was 438 days. Results: The Society of Thoracic Surgeons score was similar between the 2 groups. The device success rate (90.4% vs. 97.9%; p=0.028) was higher in the S3 than in the SXT. The S3 showed significantly fewer cases of moderate or severe paravalvular leakage (PVL) (16.7% vs.0.0%; p=0.001) than the SXT. However, effective orifice area (EOA) (2.07±0.61 vs. 1.70±0.49 cm2 ; p<0.001) was smaller in the S3. Multivariable Cox regression analysis showed the S3 was associated with significantly fewer cardiovascular mortality at 1 year compared to the SXT (5.4% vs. 1.1%; hazard ratio, 0.031; 95% confidence interval, 0.001–0.951; p=0.047). Periprocedural complication rates, composite of disabling stroke or all-cause mortality, allcause mortality, and disabling stroke at 1 year were similar between the 2 groups. Conclusions Cardiovascular mortality was lower in the S3 group than in the SXT group over 1 year of follow-up. The reduction in PVL was attributed to the higher device success rate of TAVR with the S3 valve. However, the benefit of S3 obtained at the expense of reduced EOA should be meticulously re-evaluated in larger studies during long-term follow-up.