Revised Korean Antiviral Guideline Reduces the Hepatitis B-related Hepatocellular Carcinoma Risk in Cirrhotic Patients

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.

Functional annotation of lung cancer‒associated genetic variants by cell type‒specific epigenome and long-range chromatin interactome

Functional interpretation of noncoding genetic variants associated with complex human diseases and traits remains a challenge. In an effort to enhance our understanding of common germline variants associated with lung cancer, we categorize regulatory elements based on eight major cell types of human lung tissue. Our results show that 21.68% of lung cancer‒associated risk variants are linked to noncoding regulatory elements, nearly half of which are cell type‒specific. Integrative analysis of high-resolution long-range chromatin interactome maps and single-cell RNA-sequencing data of lung tumors uncovers number of putative target genes of these variants and functionally relevant cell types, which display a potential biological link to cancer susceptibility. The present study greatly expands the scope of functional annotation of lung cancer‒associated genetic risk factors and dictates probable cell types involved in lung carcinogenesis.

Revised Korean Antiviral Guideline Reduces the Hepatitis B-related Hepatocellular Carcinoma Risk in Cirrhotic Patients

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.

Functional annotation of lung cancer‒associated genetic variants by cell type‒specific epigenome and long-range chromatin interactome

Functional interpretation of noncoding genetic variants associated with complex human diseases and traits remains a challenge. In an effort to enhance our understanding of common germline variants associated with lung cancer, we categorize regulatory elements based on eight major cell types of human lung tissue. Our results show that 21.68% of lung cancer‒associated risk variants are linked to noncoding regulatory elements, nearly half of which are cell type‒specific. Integrative analysis of high-resolution long-range chromatin interactome maps and single-cell RNA-sequencing data of lung tumors uncovers number of putative target genes of these variants and functionally relevant cell types, which display a potential biological link to cancer susceptibility. The present study greatly expands the scope of functional annotation of lung cancer‒associated genetic risk factors and dictates probable cell types involved in lung carcinogenesis.

Effect of dietary changes from high-fat diet to normal diet on breast cancer growth and metastasis / 한국영양학회지

Purpose@#It has been previously reported that breast tumor incidence, growth, and metastasis are stimulated by high-fat diet but reduced by caloric restriction. However, few studies have elucidated the effects of dietary change from a high-fat diet after breast cancer initiation. Therefore, in this study, we attempted to provide practical assistance to breast cancer prevention and management by investigating the effects of dietary change from a high-fat diet to normal diet on breast cancer growth and metastasis. @*Methods@#The experimental animals were divided into 2 groups (high-fat diet control [HFC] group and diet restriction [DR] group) and consumed a high-fat diet for 8 weeks. 4T1 cells were transplanted into subcutaneous fat or tail vein to measure the growth and metastasis of breast cancer. The HFC and DR groups continuously ingested either high-fat diet or AIG-93G diet for 5 weeks or 3 weeks, respectively. Cell proliferation and apoptosis markers from tumor tissues were analyzed by Western blot analysis. The data were analyzed using the SPSS 25.0 package program. @*Results@#The results show that the DR group significantly reduced breast tumor initiation, growth, and tumor tissue weight compared to the HFC group. The DR group suppressed tumor growth by decreasing proliferation and inducing apoptosis through down-regulation of Bcl-xL and up-regulation of caspase-3 activity. Furthermore, the DR group significantly reduced numbers of metastasized tumors in lung tissues. @*Conclusion@#These results suggest that dietary change from a high-fat diet to normal diet decreased breast growth by reducing cell proliferation and inducing apoptosis and metastasis. Taken together, these results indicate that dietary change to a low-fat and balanced diet might suppress breast tumor growth and metastasis even after tumor diagnosis.

S-1 Based Doublet as an Adjuvant Chemotherapy for Curatively Resected Stage III Gastric Cancer: Results from the Randomized Phase III POST Trial / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We conducted a randomized, multicenter, phase III trial to compare S-1 plus docetaxel (DS) with S-1 plus cisplatin (SP) as adjuvant chemotherapy for stage III gastric cancer patients. MATERIALS AND METHODS: Stage III gastric cancer patients who had received curative gastrectomy with D2 lymphadenectomy were randomized into equal groups to receive adjuvant chemotherapy of eight cycles of DS (S-1 70 mg/m2/day on days 1-14 plus docetaxel 35 mg/m2on days 1 and 8) every 3 weeks or SP (S-1 70 mg/m2/day on days 1-14 plus cisplatin 60 mg/m2on day 1) every 3 weeks. The primary endpoint was 3-year disease-free survival (DFS) rate. RESULTS: Between November 2010 and July 2013, 153 patients (75 patients to DS and 78 patients to SP) were enrolled from 8 institutions in Korea. After the capecitabine plus oxaliplatin was approved based on the CLASSIC study, itwas decided to close the study early. With a median follow-up duration of 56.9 months, the 3-year DFS rate between two groups was not significantly different (49.14% in DS group vs. 52.5% in SP group). The most common grade 3-4 adverse event was neutropenia (42.7% in DS and 38.5% in SP, p=0.351). SP group had more grade 3-4 anemia (1.3% vs. 11.5%, p=0.037), whereas grade 3-4 hand-foot syndrome (4.1% vs. 0%, p=0.025) and mucositis (10.7% vs. 2.6%, p=0.001) were more common in DS group. Fifty-one patients (68%) in DS group and 52 (66.7%) in SP group finished planned treatment. CONCLUSION: Our findings suggest that SP or DS is an effective and tolerable option for patients with curatively resected stage III gastric cancer.

Immunohistochemistry Biomarkers Predict Survival in Stage II/III Gastric Cancer Patients: From a Prospective Clinical Trial / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Identification of biomarkers to predict recurrence risk is essential to improve adjuvant treatment strategies in stage II/III gastric cancer patients. This study evaluated biomarkers for predicting survival after surgical resection. MATERIALS AND METHODS: This post-hoc analysis evaluated patients from the CLASSIC trial who underwent D2 gastrectomywith orwithout adjuvant chemotherapy (capecitabine plus oxaliplatin) at the Yonsei Cancer Center. Tumor expressions of thymidylate synthase (TS), excision repair cross-complementation group 1 (ERCC1), and programmed death-ligand 1 (PD-L1) were evaluated by immunohistochemical (IHC) staining to determine their predictive values. RESULTS: Among 139 patients, IHC analysis revealed high tumor expression of TS (n=22, 15.8%), ERCC1 (n=23, 16.5%), and PD-L1 (n=42, 30.2%) in the subset of patients. Among all patients, high TS expression tended to predict poor disease-free survival (DFS; hazard ratio [HR], 1.80; p=0.053), whereas PD-L1 positivity was associated with favorable DFS (HR, 0.33; p=0.001) and overall survival (OS; HR, 0.38; p=0.009) in multivariate Cox analysis. In the subgroup analysis, poor DFS was independently predicted by high TS expression (HR, 2.51; p=0.022) in the adjuvant chemotherapy subgroup (n=66). High PD-L1 expression was associated with favorable DFS (HR, 0.25; p=0.011) and OS (HR, 0.22; p=0.015) only in the surgery-alone subgroup (n=73). The prognostic impact of high ERCC1 expression was not significant in the multivariate Cox analysis. CONCLUSION: This study shows that high TS expression is a predictive factor for worse outcomes on capecitabine plus oxaliplatin adjuvant chemotherapy, whereas PD-L1 expression is a favorable prognostic factor in locally advanced gastric cancer patients.

Reliability of society of fetal urology and Onen grading system in fetal hydronephrosis

OBJECTIVE: To evaluate the reliability of the Society for Fetal Urology (SFU) and Onen grading systems for fetal hydronephrosis in prenatal ultrasound according to the level of experience of the examiner. METHODS: We reviewed the prenatal ultrasound images of 146 fetuses (292 kidneys) that were diagnosed as having hydronephrosis between January 2005 and December 2014. One expert and two trainees assessed the prenatal renal ultrasound images using the SFU and Onen grading systems. The three examiners independently assessed each ultrasound image with both grading systems and reassessed the same images after 7 to 14 days. Cohen's kappa statistic was used to estimate intra- and inter-observer reliability in prenatal ultrasound images according to training level. RESULTS: The intra-observer reliability of the SFU grading system (κ 0.873–0.945) showed almost perfect agreement and that of the Onen grading system (κ 0.749–0.913) showed substantial to almost perfect agreement. The overall inter-observer reliability of the SFU grading system (κ 0.620–0.825) showed substantial to almost perfect agreement and that of the Onen grading system (κ 0.618–0.724) showed substantial agreement. The weighted kappa value of inter-observer agreement was 0.223 to 0.400 for SFU grade 1 and 0.064 to 0.346 for SFU grade 3. For Onen grading, the inter-observer agreement was 0.012 to 0.214 for grade 2 and 0.193 to 0.334 for grade 3. CONCLUSION: Both the SFU and Onen grading systems showed good intra-observer agreement in prenatal ultrasonography. The inter-observer agreement was decreased in SFU grades 1 and 3 and Onen grades 2 and 3. Therefore, more focus should be given to SFU grades 1 and 3 and Onen grades 2 and 3 for trainees.

Trends in statistical methods in articles published in Archives of Plastic Surgery between 2012 and 2017

This review article presents an assessment of trends in statistical methods and an evaluation of their appropriateness in articles published in the Archives of Plastic Surgery (APS) from 2012 to 2017. We reviewed 388 original articles published in APS between 2012 and 2017. We categorized the articles that used statistical methods according to the type of statistical method, the number of statistical methods, and the type of statistical software used. We checked whether there were errors in the description of statistical methods and results. A total of 230 articles (59.3%) published in APS between 2012 and 2017 used one or more statistical method. Within these articles, there were 261 applications of statistical methods with continuous or ordinal outcomes, and 139 applications of statistical methods with categorical outcome. The Pearson chi-square test (17.4%) and the Mann-Whitney U test (14.4%) were the most frequently used methods. Errors in describing statistical methods and results were found in 133 of the 230 articles (57.8%). Inadequate description of P-values was the most common error (39.1%). Among the 230 articles that used statistical methods, 71.7% provided details about the statistical software programs used for the analyses. SPSS was predominantly used in the articles that presented statistical analyses. We found that the use of statistical methods in APS has increased over the last 6 years. It seems that researchers have been paying more attention to the proper use of statistics in recent years. It is expected that these positive trends will continue in APS.

Factors Related to Parenting Satisfaction among Mothers of Preschoolers

PURPOSE: The purpose of this study was to identify factors related to level of satisfaction among mothers of preschoolers. METHODS: Participants were 359 mothers of firstborn healthy preschoolers. The questionnaires were collected from August 1 to November 21, 2012. Data were analyzed using SPSS 20.0. RESULTS: The mean score for degree of mothers' parenting satisfaction was 5.94 out of 7. There were significant differences in the level of parenting satisfaction according to mother's job (t=2.48, p=.014), planned pregnancy (t=3.07, p=.002), number of children (t=2.22, p=.027), and parenting education (F=4.33, p=.005). The environmental variables of age of spouse (F=3.06, p=.048) and monthly income of the household (F=2.87, p=.036) also seemed to have an influence. Analysis of predictors such as the mother's job, planned pregnancy, parenting education, overall health problems, parenting stress, perception of emotional status and behaviors in children, age of spouse, and spouse's support explained 31.5% of the variance in mother's parenting satisfaction. CONCLUSION: The results suggest a need to develop nursing intervention programs for parenting stress reduction, and health programs for fathers to support mothers' child rearing.

Clinical Practice Patterns of Radiotherapy in Patients with Hepatocellular Carcinoma: A Korean Radiation Oncology Group Study (KROG 14-07) / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The aim of this study was to examine patterns of radiotherapy (RT) in Korean patients with hepatocellular carcinoma (HCC) according to the evolving guideline for HCC established by the Korean Liver Cancer Study Group-National Cancer Center (KLCSG-NCC). MATERIALS AND METHODS: We reviewed 765 patients with HCC who were treated with RT between January 2011 and December 2012 in 12 institutions. RESULTS: The median follow-up period was 13.3 months (range, 0.2 to 51.7 months). Compared with previous data between 2004 and 2005, the use of RT as a first treatment has increased (9.0% vs. 40.8%). Increased application of intensity-modulated RT resulted in an increase in radiation dose (fractional dose, 1.8 Gy vs. 2.5 Gy; biologically effective dose, 53.1 Gy10 vs. 56.3 Gy10). Median overall survival was 16.2 months, which is longer than that reported in previous data (12 months). In subgroup analysis, treatments were significantly different according to stage (p < 0.001). Stereotactic body RT was used in patients with early HCC, and most patients with advanced stage were treated with three-dimensional conformal RT. CONCLUSION: Based on the evolving KLCSG-NCC practice guideline for HCC, clinical practice patterns of RT have changed. Although RT is still used mainly in advanced HCC, the number of patients with good performance status who were treated with RT as a first treatment has increased. This change in practice patterns could result in improvement in overall survival.

Some Facts That You Might Be Unaware of About the P-Value

No abstract available.

Risk of Bladder Cancer among Patients with Diabetes Treated with a 15 mg Pioglitazone Dose in Korea: A Multi-Center Retrospective Cohort Study

It has not yet been determined whether chronic exposure to relatively low doses of pioglitazone increases risk of bladder cancer. We aimed to assess the risk of bladder cancer associated with pioglitazone in Korean patients. This was a retrospective cohort study of diabetic patients who had > or = 2 clinic visits between November 2005 and June 2011 at one of four tertiary referral hospitals in Korea. A prevalent case-control analysis nested within the cohort was conducted to further adjust confounders. A total of 101,953 control patients and 11,240 pioglitazone-treated patients were included, in which there were 237 and 30 cases of incidental bladder cancer (64.9 and 54.9 per 100,000 person-years; age, sex-adjusted HR 1.135, 95% confidence interval [CI] 0.769-1.677), respectively. In the prevalent case-control analysis nested within the cohort, use of pioglitazone for a duration of > 6 months, but not ever use of pioglitazone, was associated with an increased rate of bladder cancer as compared to never use of pioglitazone. In conclusion, we failed to exclude the possible association between use of pioglitazone for a duration of > 6 months and bladder cancer.

Image Reporting and Characterization System for Ultrasound Features of Thyroid Nodules: Multicentric Korean Retrospective Study

OBJECTIVE: The objective of this retrospective study was to develop and validate a simple diagnostic prediction model by using ultrasound (US) features of thyroid nodules obtained from multicenter retrospective data. MATERIALS AND METHODS: Patient data were collected from 20 different institutions and the data included 2000 thyroid nodules from 1796 patients. For developing a diagnostic prediction model to estimate the malignant risk of thyroid nodules using suspicious malignant US features, we developed a training model in a subset of 1402 nodules from 1260 patients. Several suspicious malignant US features were evaluated to create the prediction model using a scoring tool. The scores for such US features were estimated by calculating odds ratios, and the risk score of malignancy for each thyroid nodule was defined as the sum of these individual scores. Later, we verified the usefulness of developed scoring system by applying into the remaining 598 nodules from 536 patients. RESULTS: Among 2000 tumors, 1268 were benign and 732 were malignant. In our multiple regression analysis models, the following US features were statistically significant for malignant nodules when using the training data set: hypoechogenicity, marked hypoechogenicity, non-parallel orientation, microlobulated or spiculated margin, ill-defined margins, and microcalcifications. The malignancy rate was 7.3% in thyroid nodules that did not have suspicious-malignant features on US. Area under the receiver operating characteristic (ROC) curve was 0.867, which shows that the US risk score help predict thyroid malignancy well. In the test data set, the malignancy rates were 6.2% in thyroid nodules without malignant features on US. Area under the ROC curve of the test set was 0.872 when using the prediction model. CONCLUSION: The predictor model using suspicious malignant US features may be helpful in risk stratification of thyroid nodules.

Erratum: Image Reporting and Characterization System for Ultrasound Features of Thyroid Nodules: Multicentric Korean Retrospective Study

On page 110, the author (Won-Jin Moon)'s affiliation has been incorrectly marked as 6Department of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University, Seoul 143-729, Korea. The correct affiliation is 5Department of Radiology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul 143-729, Korea.