Seon-Heui Lee

Smoking, alcohol and gastric cancer risk in Korean men: the National Health Insurance Corporation Study

We investigated the risk of gastric cancer by subsite in relation to cigarette smoking and alcohol in a large population-based cohort of 669 570 Korean men in an insurance plan followed for an average 6.5 years, yielding 3452 new cases of gastric cancer, of which 127 were cardia and upper-third gastric cancer, 2409 were distal gastric cancer and 1007 were unclassified. A moderate association was found between smoking, cardia and upper-third (adjusted relative risk (aRR) 2.2; 95% confidence interval (CI) 1.4–3.5) and distal cancers (aRR=1.4; 95% CI=1.3–1.6). We also found a positive association between alcohol consumption and distal (aRR=1.3; 95% CI=1.2–1.5) and total (aRR=1.2; 95% CI=1.1–1.4) gastric cancer. Combined exposure to high levels of tobacco and alcohol increased the risk estimates further; cardia and upper-third gastric cancers were more strongly related to smoking status than distal gastric cancer.

CD24 Overexpression Is Associated with Poor Prognosis in Luminal A and Triple-Negative Breast Cancer

CD24 is associated with unfavourable prognoses in various cancers, but the prevalence of CD24 expression and its influence on clinical outcome in subtypes of breast cancers remain unclear. CD24 expression was analyzed by immunohistochemistry in 747 breast cancer tissues, and DNA methylation and histone modification status in the promoter region of CD24 were assessed using bisulfite sequencing and chromatin immunoprecipitation assay. 213 (28.5%) samples exhibited high CD24 expression in the membrane and/or cytoplasm of breast cancer cells, and CD24 overexpression was significantly correlated with the presence of lymph node metastasis and more advanced pathological stage. Patients with CD24-high tumours had significantly shorter patient survival than those with CD24-low tumours. Importantly, multivariate analysis that included tumour size, lymph node metastasis and chemotherapy demonstrated that high CD24 expression is independently associated with poorer survival in luminal A and triple-negative breast cancer (TNBC) subtypes. Furthermore, CD24 gene expression was associated with histone acetylation independent of DNA methylation, suggesting its epigenetic regulation in breast cancer. Our results suggest that CD24 overexpression is an independent unfavourable prognostic factor in breast cancer, especially for luminal A and TNBC subtypes, and CD24 may be a promising therapeutic target for specific subtypes of breast cancer.

A phase-1b study of everolimus plus paclitaxel in patients with small-cell lung cancer

Background:The mammalian target of rapamycin (mTOR) pathway is dysregulated in small-cell lung cancer (SCLC) and everolimus is an oral mTOR inhibitor.Methods:This phase-1b study assessed everolimus safety at the levels of 2.5, 5, or 10 mg once daily in combination with paclitaxel (175 mg m−2) once every 3 weeks in previously treated SCLC patients. The primary end point was to determine the maximum tolerated dose of everolimus.Results:Among 21 enrolled patients, common drug-related adverse events were anaemia, neutropenia, thrombocytopenia, pain, hyperglycemia, and stomatitis. Out of 11 evaluable patients treated with everolimus at the level of 5 mg, 1 patient experienced dose-limiting toxicity (DLT) of grade 4 febrile neutropenia and grade 3 thrombocytopenia. The other two DLTs (grade 4 thrombocytopenia and grade 3 hyperglycemia) occurred in two out of three patients receiving everolimus 10 mg. The overall objective response rate was 28%.Conclusion:Everolimus showed an acceptable safety profile and preliminary antitumour activity at the dose of 5 mg once daily when combined with 3-weekly paclitaxel 175 mg m−2 in patients with SCLC.

Cosmetic regional conjunctivectomy with postoperative mitomycin C application with or without bevacizumab injection.

PURPOSE To evaluate the complications of cosmetic wide conjunctivectomy and postoperative topical mitomycin C application with or without bevacizumab injection. DESIGN Cross-sectional cohort study. METHODS Medical records of 1713 consecutive subjects who received cosmetic wide conjunctivectomy plus postoperative topical mitomycin C by a single surgeon at a single center with or without bevacizumab injection from November 2007 to May 2010 were reviewed. A telephone interview was conducted with 557 of the subjects who could be contacted and agreed to participate in the study. Complications, recurrences, and patient satisfaction were the main outcome measures. RESULTS A total of 1713 consecutive patients underwent cosmetic wide conjunctivectomy to treat conjunctival hyperemia. Ocular diagnoses in the medical records at the time of surgery included hyperemia (8.8%), pterygium (14.0%), dry eye (3.5%), pinguecula (1.5%), and conjunctival disorder (23.3%). For the remaining 48.9% of subjects, the diagnosis was not mentioned, or the surgical procedure was for cosmetic purposes. Patients were followed for a mean of 10.9 months (range, 0-30.3 months). The overall complication rate was 82.9%, of which 55.6% were considered severe (fibrovascular conjunctival tissue proliferation, 43.8%; scleral thinning, 4.4%; scleral thinning with calcified plaques, 6.2%; intraocular pressure elevation, 13.1%; diplopia, 3.6%; and recurrence of hyperemic conjunctiva, 28.1%). CONCLUSIONS Cosmetic wide conjunctivectomy plus postoperative topical mitomycin C with or without bevacizumab injection has a high rate of complications and reoperations.

A Systematic Review of Interspinous Dynamic Stabilization

Background A systematic literature review of interspinous dynamic stabilization, including DIAM, Wallis, Coflex, and X-STOP, was conducted to assess its safety and efficacy. Methods The search was done in Korean and English, by using eight domestic databases which included KoreaMed and international databases, such as Ovid Medline, Embase, and the Cochrane Library. A total of 306 articles were identified, but the animal studies, preclinical studies, and studies that reported the same results were excluded. As a result, a total of 286 articles were excluded and the remaining 20 were included in the final assessment. Two assessors independently extracted data from these articles using predetermined selection criteria. Qualities of the articles included were assessed using Scottish Intercollegiate Guidelines Network (SIGN). Results The complication rate of interspinous dynamic stabilization has been reported to be 0% to 32.3% in 3- to 41-month follow-up studies. The complication rate of combined interspinous dynamic stabilization and decompression treatment (32.3%) was greater than that of decompression alone (6.5%), but no complication that significantly affected treatment results was found. Interspinous dynamic stabilization produced slightly better clinical outcomes than conservative treatments for spinal stenosis. Good outcomes were also obtained in single-group studies. No significant difference in treatment outcomes was found, and the studies compared interspinous dynamic stabilization with decompression or fusion alone. Conclusions No particular problem was found regarding the safety of the technique. Its clinical outcomes were similar to those of conventional techniques, and no additional clinical advantage could be attributed to interspinous dynamic stabilization. However, few studies have been conducted on the long-term efficacy of interspinous dynamic stabilization. Thus, the authors suggest further clinical studies be conducted to validate the theoretical advantages and clinical efficacy of this technique.

A new molecular prognostic score for predicting the risk of distant metastasis in patients with HR+/HER2− early breast cancer

To make an optimal treatment decision for early stage breast cancer, it is important to identify risk of recurrence. Here, we developed and validated a new prognostic model for predicting the risk of distant metastasis in patients with pN0-N1, hormone receptor-positive, HER2-negative (HR+/HER2−) breast cancer treated with hormone therapy alone. RNA was extracted from formalin-fixed, paraffin-embedded tumor tissues and gene expression was measured by quantitative real-time reverse transcription-PCR. The relative expression of six novel prognostic genes was combined with two clinical variables (nodal status and tumor size) to calculate a risk score (BCT score). In the validation cohort treated with hormone therapy alone, the 10 year rate of distant metastasis in the high-risk group (26.3%) according to BCT score was significantly higher than that in the low-risk group (3.8%) (P < 0.001). Multivariate analysis adjusted for clinical variables revealed that BCT score is an independent predictor of distant metastasis. Moreover, the C-index estimate revealed that BCT score has a prognostic power superior to that of prognostic models based on clinicopathological parameters. The BCT score outperforms prognostic models based on traditional clinicopathological factors and predicts the risk of distant metastasis in patients with HR+/HER2− early breast cancer.

Impact of Market Competition on Continuity of Care and Hospital Admissions for Asthmatic Children: A Longitudinal Analysis of Nationwide Health Insurance Data 2009-2013.

Background Ambulatory care-sensitive conditions, including asthma, can be managed with timely and effective outpatient care, thereby reducing the need for hospitalization. Objective This study assessed the relationship between market competition, continuity of care (COC), and hospital admissions in asthmatic children according to their health care provider. Methods A longitudinal design was employed with a 5-year follow-up period, between 2009 and 2013, under a Korean universal health insurance program. A total of 253 geographical regions were included in the analysis, according to data from the Korean Statistical Office. Data from 9,997 patients, aged ≤ 12 years, were included. We measured the COC over a 5-year period using the Usual Provider Continuity (UPC) index. Random intercept models were calculated to assess the temporal and multilevel relationship between market competition, COC, and hospital admission rate. Results Of the 9,997 patients, 243 (2.4%) were admitted to the hospital in 2009. In the multilevel regression analysis, as the Herfindahl–Hirschman Index increased by 1,000 points (denoting decreased competitiveness), UPC scores also increased (ß = 0.001; p < 0.0001). In multilevel logistic regression analysis, the adjusted odds ratio (OR) for hospital admissions for individuals with lower COC scores (≥ 2 ambulatory visits and a UPC index score of < 1) was 3.61 (95% CI: 2.98–4.38) relative to the reference group (≥ 2 ambulatory visits and a UPC index score of 1). Conclusions Market competition appears to reduce COC; decreased COC was associated with a higher OR for hospital admissions.

Intra-Articular Injection of Bone Marrow-Derived Mesenchymal Stem Cells Leading to Better Clinical Outcomes without Difference in MRI Outcomes from Baseline in Patients with Knee Osteoarthritis

Purpose Bone marrow (BM) is frequently used as a source of mesenchymal stem cells (MSCs) because they have a high potential for differentiation. However, it is unclear whether BM-derived MSCs lead to better clinical and magnetic resonance imaging (MRI) outcomes postoperatively. Materials and Methods This meta-analysis compared the clinical and MRI outcomes in patients with knee osteoarthritis (OA) treated with BM-derived MSCs. Eight studies comparing the clinical and MRI outcomes assessed with various measurement tools in patients with knee OA treated with BM-derived MSCs were included. Results The range of motion (95% confidence interval [CI], −13.05 to 4.24; p=0.32) and MRI outcomes (95% CI, −0.16 to 1.40; p=0.12) did not differ significantly between the baseline and final follow-up. In contrast, pain (95% CI, 0.89 to 1.87; p<0.001) and functional outcomes (95% CI, 0.70 to 2.07; p<0.001) were significantly improved at the final follow-up when compared to the baseline. Conclusions This meta-analysis found no significant difference in the tested range of motion and MRI outcomes between the baseline and the final follow-up in patients treated with BM-derived MSCs, whereas significant functional improvement and pain relief were noted when compared with the baseline. Thus, BM-derived MSCs appear to be a viable alternative for patients with knee OA, although long-term and high-quality randomized controlled trials are needed to confirm the clinical benefits.

Disparities in socioeconomic status and neighborhood characteristics affect all-cause mortality in patients with newly diagnosed hypertension in Korea: a nationwide cohort study, 2002–2013

BackgroundPrevious studies have shown that contextual factors and individual socioeconomic status (SES) were associated with mortality in Western developed countries. In Korea, there are few empirical studies that have evaluated the association between SES and health outcomes.MethodsWe conducted cohort study to investigate the socioeconomic disparity in all-cause mortality for patients newly diagnosed with hypertension in the setting of universal health care coverage. We used stratified random sample of Korean National Health Insurance enrollees (2002–2013). We included patients newly diagnosed with hypertension (n = 28,306) from 2003–2006, who received oral medication to control their hypertension. We generated a frailty model using Cox’s proportional hazard regression to assess risk factors for mortality.ResultsA total of 7,825 (27.6%) of the 28,306 eligible subjects died during the study period. Compared to high income patients from advantaged neighborhoods, the adjusted hazard ratio (HR) for high income patients from disadvantaged neighborhoods was 1.10 (95% CI, 1.00–1.20; p-value = 0.05). The adjusted HR for middle income patients who lived in advantaged versus disadvantaged neighborhoods was 1.17 (95% CI, 1.08–1.26) and 1.27 (95% CI, 1.17–1.38), respectively. For low income patients, the adjusted HR for patients who lived in disadvantaged neighborhoods was higher than those who lived in advantaged neighborhoods (HR, 1.35; 95% CI, 1.22–1.49 vs HR, 1.28; 95% CI, 1.16–1.41).ConclusionsNeighborhood deprivation can exacerbate the influence of individual SES on all-cause mortality among patients with newly diagnosed hypertension.

A Systematic Review on the Effectiveness of Detection of M. tuberculosis and Rifampin Resistance Using Xpert MTB/RIF

Background: The purpose of this study was to evaluate the effectiveness of Xpert MTB/RIF (Cepheid, USA) in the detection of Mycobacterium tuberculosis and to determine rifampin resistance. Methods: The literature review covered the period from 16 August 2011 to 1 October 2011, and eight domestic databases and foreign databases including Ovid-Medline, Embase, and Cochrane Library were used. Key words, such as ‘Rifampin, Polymerase Chain Reaction,’ ‘GeneXpert’ and ‘Xpert MTB-RIF’ were used to search a total of 1,385 documents. The SIGN (Scottish Intercollegiate Guidelines Network) tool was used to evaluate the quality of the 20 selected studies. Results: Test accuracy for the detection of M. tuberculosis was assessed on the basis of 20 studies using the M. tuberculosis culture test as the reference standard. The acid-fast bacteria smearing test had a sensitivity in the range of 0.69-1.00, specificity in the range of 0.72-1.00 and test accuracy in the range of 0.75-1.00. Test accuracy regarding rifampin resistance was assessed on the basis of 17 studies. Using an anti-tuberculosis agent sensitivity test as the reference standard, the sensitivity, specificity and test accuracy of real-time, nested PCR were in the ranges of 0.75-1.00, 0.96-1.00 and 0.95-1.00, respectively. Conclusion: Xpert MTB/RIF is a useful test for patients suspected of having rifampin-resistant tuberculosis. (Ann Clin Microbiol 2014;17:42-49)