Hyunsun Lim

Factors Associated with False Positives in Retinal Nerve Fiber Layer Color Codes from Spectral-Domain Optical Coherence Tomography

PURPOSE To determine the factors that contribute to false-positive retinal nerve fiber layer (RNFL) color code results from spectral-domain optical coherence tomography (OCT). DESIGN A prospective, cross-sectional study. PARTICIPANTS This study included 149 eyes from 77 healthy participants. METHODS Participants, who were consecutively enrolled from June 2009 to December 2009, underwent Cirrus OCT. Recorded demographic and clinical factors included age, gender, eye side, intraocular pressure, central corneal thickness, spherical equivalent, axial length, anterior chamber depth, disc area, and the extent of retinal vasculature. MAIN OUTCOME MEASURES An abnormal finding in RNFL color codes was defined as ≥1 yellow or red sectors by quadrant and clock-hour maps and a wedge-shaped color pattern represented by yellow or red in the deviation map. The incidence of false-positive color codes was determined. The influence of clinical and demographic factors on the incidence of false-positive RNFL color codes was assessed using generalized linear mixed model analysis. RESULTS The false-positive rate for ≥1 of the quadrant, clock-hour, and deviation maps was 26.2%. Longer axial length and smaller disc area were significantly associated with an increased incidence of false-positives when other factors were controlled (odds ratios, 2.422 and 0.165; P = 0.008 and 0.035, respectively). CONCLUSIONS The factors that significantly affected the false-positive RNFL color code results using spectral-domain OCT were axial length and disc area, which may significantly affect the specificity of spectral-domain OCT. Therefore, axial length and disc area should be considered during RNFL thickness profile analysis.

Individualized risk prediction model for lung cancer in Korean men.

Purpose Lung cancer is the leading cause of cancer deaths in Korea. The objective of the present study was to develop an individualized risk prediction model for lung cancer in Korean men using population-based cohort data. Methods From a population-based cohort study of 1,324,804 Korean men free of cancer at baseline, the individualized absolute risk of developing lung cancer was estimated using the Cox proportional hazards model. We checked the validity of the model using C statistics and the Hosmer–Lemeshow chi-square test on an external validation dataset. Results The risk prediction model for lung cancer in Korean men included smoking exposure, age at smoking initiation, body mass index, physical activity, and fasting glucose levels. The model showed excellent performance (C statistic = 0.871, 95% CI = 0.867–0.876). Smoking was significantly associated with the risk of lung cancer in Korean men, with a four-fold increased risk in current smokers consuming more than one pack a day relative to non-smokers. Age at smoking initiation was also a significant predictor for developing lung cancer; a younger age at initiation was associated with a higher risk of developing lung cancer. Conclusion This is the first study to provide an individualized risk prediction model for lung cancer in an Asian population with very good model performance. In addition to current smoking status, earlier exposure to smoking was a very important factor for developing lung cancer. Since most of the risk factors are modifiable, this model can be used to identify those who are at a higher risk and who can subsequently modify their lifestyle choices to lower their risk of lung cancer.

Development of Multiplexed Bead-Based Immunoassays for the Detection of Early Stage Ovarian Cancer Using a Combination of Serum Biomarkers

CA125 as a biomarker of ovarian cancer is ineffective for the general population. The aim of this study was to evaluate multiplexed bead-based immunoassay of multiple ovarian cancer-associated biomarkers such as transthyretin and apolipoprotein A1, together with CA125, to improve the identification and evaluation of prognosis of ovarian cancer. We measured the serum levels of CA125, transthyretin, and apolipoprotein A1 from the serum of 61 healthy individuals, 84 patients with benign ovarian disease, and 118 patients with ovarian cancer using a multiplex liquid assay system, Luminex 100. The results were then analyzed according to healthy and/or benign versus ovarian cancer subjects. When CA125 was combined with the other biomarkers, the overall sensitivity and specificity were significantly improved in the ROC curve, which showed 95% and 97% sensitivity and specificity, respectively. At 95% specificity for all stages the sensitivity increased to 95.5% compared to 67% for CA125 alone. For stage I+II, the sensitivity increased from 30% for CA125 alone to 93.9%. For stage III+IV, the corresponding values were 96.5% and 91.6%, respectively. Also, the three biomarkers were sufficient for maximum separation between noncancer (healthy plus benign group) and stage I+II or all stages (I−IV) of disease. The new combination of transthyretin, and apolipoprotein A1 with CA125 improved both the sensitivity and the specificity of ovarian cancer diagnosis compared with those of individual biomarkers. These findings suggest the benefit of the combination of these markers for the diagnosis of ovarian cancer.

Papillary Thyroid Microcarcinomas Are Different from Latent Papillary Thyroid Carcinomas at Autopsy

The aim of this study was to review the literature of latent papillary thyroid carcinomas (PTCs) discovered at autopsy and describe the available pathologic and demographic differences from a group of papillary thyroid microcarcinomas (PTMCs) the reported in a previous publication. We searched the PubMed for published articles describing latent thyroid carcinomas detected at autopsy. Meta-analysis was performed to identify differences between the clinicopathologic features of PTMCs analyzed previously in our institution (Group I) and those of latent PTCs described in autopsy studies (Group II). We identified 1,355 patients with PTMC (Group I) and 989 with latent PTCs (Group II). Mean patient age was 47.3 yr in Group I and 64.5 yr in Group II. The male:female ratio was 1:10.9 in Group I and 1:1 in Group II. Most PTMCs (67.6%) were larger than 0.5 cm in size, whereas most latent PTCs were <1-3 mm in diameter. The rates of multifocality were 24.7% in Group I and 30.5% in Group II, and the rates of cervical lymph node metastasis were 33.4% in Group I and 10.0% in Group II. Currently available data indicated that clinically evident PTMCs differ from latent PTCs detected at autopsy. Therefore, these two entities should be regarded as different.

Optimal indication of thyroglobulin measurement in fine-needle aspiration for detecting lateral metastatic lymph nodes in patients with papillary thyroid carcinoma

The purpose of this study was to evaluate optimal indication of thyroglobulin (Tg) measurement in fine‐needle aspiration (FNA) for detecting lateral metastatic lymph nodes in patients with papillary thyroid carcinoma (PTC).

Carbonic anhydrase XII expression is associated with histologic grade of cervical cancer and superior radiotherapy outcome.

BackgroundTo investigate whether expression of carbonic anhydrase XII (CA12) is associated with histologic grade of the tumors and radiotherapy outcomes of the patients with invasive cervical cancer.MethodsCA12 expression was examined by immunohistochemical stains in cervical cancer tissues from 183 radiotherapy patients. Histological grading was classified as well (WD), moderately (MD) or poorly differentiated (PD). Oligonucleotide microarray experiment was performed using seven cervical cancer samples to examine differentially expressed genes between WD and PD cervical cancers. The association between CA12 and histological grade was analyzed by chi-square test. CA12 and histological grades were analyzed individually and as combined CA12 and histologic grade categories for effects on survival outcome.ResultsImmunohistochemical expression of CA12 was highly associated with the histologic grade of cervical cancer. Lack of CA12 expression was associated with PD histology, with an odds ratio of 3.9 (P = 0.01). Microarray analysis showed a fourfold reduction in CA12 gene expression in PD tumors. CA12 expression was marginally associated with superior disease-free survival. Application of the new combined categories resulted in further discrimination of the prognosis of patients with moderate and poorly differentiated tumor grade.ConclusionsOur study indicates that CA12 may be used as a novel prognostic marker in combination with histologic grade of the tumors.

Persistent human papillomavirus DNA is associated with local recurrence after radiotherapy of uterine cervical cancer.

Human papillomavirus (HPV) DNA is considered as a hallmark of cervical cancer. We investigated whether persistent HPV DNA at the cervix is associated with local recurrence after radiotherapy in patients with locally advanced cervical cancer. A total of 156 patients with HPV‐positive cervical cancer (International Federation of Gynecology and Obstetrics stage IB–IVB) treated with radiotherapy between July 2003 and December 2006 were analyzed. HPV DNA was measured prior to radiotherapy and after completion of radiotherapy. The results of HPV DNA test at postradiotherapy 1, 3, 6 and 12 months were analyzed individually for association with local recurrence‐free survival (LRFS). In addition, the result of any last follow‐up HPV test within 24 months postradiotherapy was defined as the overall status of HPV at 24 months and was also analyzed for association with LRFS. HPV DNA was cleared in 127 patients (81.4%) and persistent in 29 patients (18.6%) by 24 months. In 18 patients with local recurrences, 14 patients (78%) showed positive HPV tests at 1–3 months. Among the various time points analyzed, a positive HPV test at 3 months was the most accurate predictor of local recurrence. Multivariate analysis indicated that overall status of HPV at 24 months, low HPV viral load and histologic grade as being significantly related to poor LRFS. In HPV‐positive cervical carcinoma treated primarily with radiotherapy, persistent HPV DNA within 24 months after treatment indicates a high risk of local recurrence. Diagnostic accuracy of HPV test was highest at 3 months.

Urinary iodine and sodium status of urban Korean subjects: a pilot study.

OBJECTIVES We estimated iodine status of Korean population by determining the concentration of spot urinary iodine (UI) with a reliable method based on the Sandell-Kolthoff reaction. MATERIALS AND METHODS A total of 540 urine samples from apparently healthy subjects were collected, and UI, urinary sodium (UNa), and urinary creatinine (UCr) were determined from those samples and analyzed with age. RESULTS There were significant decreases in either UI (P<0.0001), UI/UCr ratio (P=0.0001), UNa (P<0.0001), or UNa/Cr ratio (P=0.0001) in younger subjects than older ones. The median value of UI was 267.6 μg/L, but the median UI of the younger group (191.8 μg/L) was significantly decreased compared to that of the older group (383.9 μg/L). CONCLUSIONS This study showed that the median of UI in Korean urban population was in a more than adequate iodine nutritional state, but UI was significantly different between the younger age group and the older age group.

An Epidemiological Analysis of Hepatitis A Virus Serologic Markers during the Recent Four Years in Korea

BACKGROUND To establish effective preventive measures for hepatitis A virus (HAV) infection, a nationwide epidemiologic study on seroprevalence of anti-HAV and the disease prevalence is needed. The aim of this study was to analyze the recent sero-epidemiological changes of hepatitis A markers in Korea. METHODS The results of 11,068 anti-HAV total and 32,360 anti-HAV IgM tests by electro-chemiluminescence immunoassay (ECLIA) that had been requested in recent four years (2005-2008) to a reference medical laboratory from 1,699 institutions nationwide were retrospectively analyzed according to the distribution of year, sex, and age groups. RESULTS The overall positive rate of anti-HAV total was 62.8%. The overall positive rate of anti-HAV IgM was 11.0%, showing a significantly increasing trend by year: 7.7%, 10.9%, 8.9%, and 14.3% in 2005, 2006, 2007, and 2008, respectively (P<0.0001). The positive rate of anti-HAV IgM was higher in male than in female subjects (11.8% vs 10.0%, P<0.0001), and 81.8% (2,916/3,566) of the anti-HAV IgM positive results were observed in the age groups of 21-40 yr. The annual positive rates of anti-HAV total and anti-HAV IgM showed significantly decreasing and increasing trends, respectively, in the age groups of > or = 21 yr. CONCLUSION In accordance with a decreasing sero-positivity of anti-HAV total, the prevalence of acute hepatitis A virus infection has been considerably increased during the recent four years in the age groups of > or = 21 yr. The results of this study could be used effectively as a basic data for establishing effective preventive measures for hepatitis A including vaccination in these susceptible age groups.

Gene-Based Rare Allele Analysis Identified a Risk Gene of Alzheimer’s Disease

Alzheimer’s disease (AD) has a strong propensity to run in families. However, the known risk genes excluding APOE are not clinically useful. In various complex diseases, gene studies have targeted rare alleles for unsolved heritability. Our study aims to elucidate previously unknown risk genes for AD by targeting rare alleles. We used data from five publicly available genetic studies from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the database of Genotypes and Phenotypes (dbGaP). A total of 4,171 cases and 9,358 controls were included. The genotype information of rare alleles was imputed using 1,000 genomes. We performed gene-based analysis of rare alleles (minor allele frequency≤3%). The genome-wide significance level was defined as meta P<1.8×10–6 (0.05/number of genes in human genome = 0.05/28,517). ZNF628, which is located at chromosome 19q13.42, showed a genome-wide significant association with AD. The association of ZNF628 with AD was not dependent on APOE ε4. APOE and TREM2 were also significantly associated with AD, although not at genome-wide significance levels. Other genes identified by targeting common alleles could not be replicated in our gene-based rare allele analysis. We identified that rare variants in ZNF628 are associated with AD. The protein encoded by ZNF628 is known as a transcription factor. Furthermore, the associations of APOE and TREM2 with AD were highly significant, even in gene-based rare allele analysis, which implies that further deep sequencing of these genes is required in AD heritability studies.