Papillary thyroid carcinoma is the most common type of thyroid cancer, for which surgery following preoperative staging and risk assessment is the standard treatment. Afatinib is an orally active irreversible ErbB-family inhibitor that binds to the kinase domain of epidermal growth factor receptors (EGFRs), HER2, and HER4, and has been approved as monotherapy for the treatment of locally advanced or metastatic non-small cell lung cancer with activated EGFR mutations. Recently, we observed an unexpected effect of afatinib administered to treat lung cancer on untreated papillary thyroid carcinoma.

Background/Aims: The mucoprotective drug rebamipide is used to treat gastritis and peptic ulcers. We compared the efficacy of Mucosta Ⓡ (rebamipide 100 mg) and its new formulation, AD-203 (rebamipide 150 mg), in treating erosive gastritis. Methods: This double-blind, active control, noninferiority, multicenter, phase 3 clinical trial randomly assigned 475 patients with endoscopically proven erosive gastritis to two groups: AD-203 twice daily or Mucosta Ⓡ thrice daily for 2 weeks. The intention-to-treat (ITT) analysis included 454 patients (AD-203, n=229; Mucosta Ⓡ , n=225), and the per-protocol (PP) analysis included 439 patients (AD-203, n=224; Mucosta Ⓡ , n=215). The posttreatment assessments included the primary (erosion improvement rate) and secondary endpoints (erosion and edema cure rates; improvement rates of redness, hemorrhage, and gastrointestinal symptoms). Drug-related adverse events were evaluated. Results: According to the ITT analysis, the erosion improvement rates (posttreatment) in AD-203-treated and Mucosta Ⓡ -treated patients were 39.7% and 43.8%, respectively. According to the PP analysis, the erosion improvement rates (posttreatment) in AD-203-treated and Mucosta Ⓡ -treated patients were 39.3% and 43.7%, respectively. The one-sided 97.5% lower limit for the improvement rate difference between the study groups was −4.01% (95% confidence interval [CI], –13.09% to 5.06%) in the ITT analysis and −4.44% (95% CI, –13.65% to 4.78%) in the PP analysis. The groups did not significantly differ in the secondary endpoints in either analysis. Twenty-four AD-203-treated and 20 Mucosta Ⓡ -treated patients reported adverse events but no serious adverse drug reactions; both groups presented similar adverse event rates. Conclusions The new formulation of rebamipide 150 mg (AD-203) twice daily was not inferior to rebamipide 100 mg (Mucosta Ⓡ ) thrice daily. Both formulations showed a similar efficacy in treating erosive gastritis.

BACKGROUND/AIMS: Currently, a new over-the-scope clip (OTSC) system has been introduced. This system has been used for gastrointestinal perforations and fistulas in other countries. The aim of our study is to examine the therapeutic success rate of endoscopic treatment using the OTSC system in Korea. METHODS: This was a multicenter prospective study. A total of seven endoscopists at seven centers performed this procedure. RESULTS: A total of 19 patients were included, with gastrointestinal leakages from anastomosis sites, fistulas, or esophageal perforations due to Boerhaave’s syndrome. Among these, there were three gastrojejunostomy sites, three esophagojejunostomy sites, four esophagogastrostomy sites, one esophagocolonostomy site, one jejuno-jejunal site, two endoscopic full thickness resection site closures, one Boerhaave’s syndrome, two esophago-bronchial fistulas, one gastrocolonic fistula, and one colonopseudocyst fistula. The size of the leakage ranged from 5 to 30 mm. The median procedure time was 16 min. All cases were technically successful. Complete closure of the leak was achieved in 14 of 19 patients using OTSC alone. CONCLUSIONS: The OTSC system is a safe and effective method for the management of gastrointestinal leakage, especially in cases of anastomotic leakage after surgery.
Anastomotic Leak ; Esophageal Perforation ; Fistula ; Gastric Bypass ; Humans ; Korea ; Methods ; Prospective Studies

PURPOSE: The purpose of this study was to analyze the diagnostic availability and to examine the co-relation between pedobaragraphy and radiography of pediatric flexible flatfoot. MATERIALS AND METHODS: Seventeen patients and ten normal children were studied. In radiographic evaluation, the talo-1st metatarsal angle was measured on anteroposterior radiographs; and the talo-1st metatarsal angle, the talo-horizontal angle, the calcaneal pitch, and the talocalcaneal angle were measured on lateral radiographs. In pedobarography, foot pressures were subdivided into eight areas for measurement of contact time, ratio of measured area and to investigate the relation between the degree of the medial deviation of the Center of pressure line and the radiographic measurements. RESULTS: Flat foot group and normal group showed statistically significant difference in every angle measured in lateral radiographs. The foot pressure ratios of the lateral sides in forefoot and the medial and lateral sides of midfoot and the medial side of hindfoot between the flexible flatfoot group and normal group showed statistically significant difference in pedobarography and ratio of contact area in forefoot and hindfoot showed significant change in statistics but no changes in contact time. The relation between pedobarography and radiography was investigated: foot pressure of the medial and lateral side of forefoot and the talocalcaneal angle showed significant relation in statistics and foot pressure of the medial and lateral side of mid foot and every angle measured in lateral radiographs showed significant relation in statistics. Contact time of midfoot and every radiographic value measured in lateral radiograph showed significant relation in statistics and contact area of forefoot and midfoot showed significant relation with every radiographic value measured in lateral radiographs. In addition, medial deviation of center of pressure line showed significant relation in statistics with talus-first metatarsal angle measured on anteroposterior radiographs and talo-horizontal angle and talus-first metatarsal angle measured on lateral radiographs. CONCLUSION: The results of this study showed correlation between radiologic methods and pedobarography in diagnosis of pediatric flexible flatfoot and pedobarography is an useful tool in quantitative and qualitative analysis of the degree of foot deformity and medial deviation of center of pressure line.
Child ; Diagnosis ; Flatfoot* ; Foot ; Foot Deformities ; Humans ; Metatarsal Bones ; Radiography

PURPOSE: This study was designed to determine the relationship of cigarette smoking to the frequency and qualitative differences among KRAS mutations in lung adenocarcinomas from Korean patients. MATERIALS AND METHODS: Detailed smoking histories were obtained from 200 consecutively enrolled patients with lung adenocarcinoma according to a standard protocol. EGFR (exons 18 to 21) and KRAS (codons 12/13) mutations were determined via direct-sequencing. RESULTS: The incidence of KRAS mutations was 8% (16 of 200) in patients with lung adenocarcinoma. KRAS mutations were found in 5.8% (7 of 120) of tumors from never-smokers, 15% (6 of 40) from former-smokers, and 7.5% (3 of 40) from current-smokers. The frequency of KRAS mutations did not differ significantly according to smoking history (p=0.435). Never-smokers were significantly more likely than former or current smokers to have a transition mutation (G-->A or C-->T) rather than a transversion mutation (G-->T or G-->C) that is known to be smoking-related (p=0.011). In a Cox regression model, the adjusted hazard ratios for the risk of progression with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were 0.24 (95% CI, 0.14-0.42; p<0.001) for the EGFR mutation and 1.27 (95% CI, 0.58-2.79; p=0.537) for the KRAS mutation. CONCLUSION: Cigarette smoking did not influence the frequency of KRAS mutations in lung adenocarcinomas in Korean patients, but influenced qualitative differences in the KRAS mutations.
Adenocarcinoma/drug therapy/etiology/*genetics/pathology ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group/genetics ; Female ; Humans ; Incidence ; Lung Neoplasms/drug therapy/etiology/*genetics/pathology ; Male ; Middle Aged ; *Mutation ; Mutation Rate ; Proportional Hazards Models ; Proto-Oncogene Proteins/*genetics ; Receptor, Epidermal Growth Factor/antagonists & inhibitors/genetics ; Smoking/adverse effects/*genetics ; Treatment Outcome ; ras Proteins/*genetics

PURPOSE: Mutations in the epidermal growth factor receptor (EGFR) have been confirmed as predictors of the efficacy of treatment with EGFR-tyrosine kinase inhibitors (TKIs). We investigated whether polymorphisms of the EGFR gene were associated with clinical outcomes in non-small cell lung cancer (NSCLC) patients treated with EGFR-TKI. MATERIALS AND METHODS: A polymorphic dinucleotide repeat in intron 1 [CA simple sequence repeat in intron 1(CA-SSR1)] in intron 1 and single nucleotide polymorphisms (SNP-216) in the promoter region of the EGFR gene were evaluated in 71 NSCLC patients by restriction fragment length polymorphism and DNA sequencing. The relationship between genetic polymorphisms and clinical outcomes of treatment with EGFR-TKIs was evaluated. RESULTS: SNP-216G/T polymorphisms were associated with the efficacy of EGFR-TKI. The response rate for the SNP-216G/T tended to be higher than that for G/G (62.5% vs. 27.4%, p=0.057). The SNP-216G/T genotype was also associated with longer progression-free survival compared with the GG genotype (16.7 months vs. 5.1 months, p=0.005). However, the length of CA-SSR1 was not associated with the efficacy of EGFR-TKI. CONCLUSION: SNP-216G/T polymorphism was a potential predictor of clinical outcomes in NSCLC patients treated with EGFR-TKI.
Adult ; Aged ; Aged, 80 and over ; Female ; Genotype ; Humans ; Introns/genetics ; Kaplan-Meier Estimate ; Lung Neoplasms/*drug therapy/*genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide/genetics ; Protein Kinase Inhibitors/*therapeutic use ; Receptor, Epidermal Growth Factor/*antagonists & inhibitors/*genetics ; Treatment Outcome

BACKGROUND/AIMS: In Asian countries including Korea, the prevalence of gastroesophageal reflux disease (GERD) is on the rise and its clinical impact has been emphasized. The purpose of this study was to investigate the clinical characteristics of esophagitis patients with or without symptoms, and their association with psychological factors. METHODS: Subjects diagnosed as erosive esophagitis of Los Angeles-A or more in screening by upper gastrointestinal endoscopy were enrolled. Questionnaires regarding GERD symptoms and Symptom Checklist-90-Revision were used to identify the presence of psychological symptoms. RESULTS: There was no difference between the subjects' general characteristics (gender, age, body mass index, smoking and alcohol intake) according to the existence of typical symptoms in these patients with erosive esophagitis. Patients with typical GERD symptoms were more likely to have atypical symptoms, dyspepsia and higher scores on psychological symptoms (somatization, obsessive-compulsiveness and phobic anxiety) than those without. CONCLUSIONS: Psychological symptoms and other gastrointestinal symptoms should be considered in the patients with erosive esophagitis.
Asian Continental Ancestry Group ; Body Mass Index ; Dyspepsia ; Endoscopy, Gastrointestinal ; Esophagitis ; Gastroesophageal Reflux ; Humans ; Korea ; Mass Screening ; Prevalence ; Psychological Tests ; Surveys and Questionnaires ; Smoke ; Smoking

PURPOSE: Free-floating thrombus (FFT) of the aorta is very rare but has a high risk of distal embolization. While the necessity of treating such a condition is evident, the diagnostic and therapeutic modalities remain controversial. Thus, we reviewed seven cases of FFT of the aorta. METHODS: A retrospective study was performed usings even patients diagnosed with FFT of the aorta at the Catholic University of Korea between January 1999 and December 2008. We excluded those patients who had thrombi with concomitant atherosclerotic or aneurysmal aorta. RESULTS: The mean patient age was 59.6+/-13.6 years old. The male-to-female ratio was 3:4. Embolization to arteries of the extremities occurred in two patients and to visceral arteries in four patients. Of these seven patients, four were initially treated with anticoagulation, and two were initially treated with thrombectomy; one patient refused any kind of treatment. Of the four patients treated with anticoagulation, three experienced complete dissolution of the thrombi while anticoagulation proved ineffective in the remaining patient who subsequently underwent thrombectomy. In all of the three patients who had received thrombectomy, postoperative anticoagulation was employed. There was no recurrence of FFT of the aorta during the follow-up period. CONCLUSION: Were commend systemic anticoagulation with low molecular weight heparin (LMWH) as the first line of treatment for FFT of the aorta. If the thrombus persists or recurrent embolism occurs during anticoagulation therapy, surgery should be undertaken.
Aneurysm ; Aorta* ; Arteries ; Embolism ; Extremities ; Follow-Up Studies ; Heparin, Low-Molecular-Weight ; Humans ; Korea ; Recurrence ; Retrospective Studies ; Thrombectomy ; Thrombosis*

BACKGROUND/AIMS: DNA double strand break (DSB) is one of the critical types of DNA damage. When unrepaired DSB is accumulated in the nucleus of the cells having mutations in such genes as p53, it will lead to chromosomal instability and further more to mutation of tumor-activating genes resulting in tumorogenesis. Some of malignant cancers and its premalignant lesions were proven to have DSB in their nuclei. The aim of this study was to define the differences in expression of 53BP1 and gamma-H2AX, the markers of DSB, among normal, gastric adenoma, and gastric adenocarcinoma tissues. METHODS: Tissue microarray was made with the tissues taken from 121 patients who underwent gastrectomy for gastric adenocarcinoma, and 51 patients who underwent endoscopic mucosal resection for gastric adenoma. Immunochemical stain was performed for the marker of DSB, 53BP1 and gamma-H2AX in the tissue microarray. The normal tissues were collected from histologically confirmed tissues with no cellular atypia obtained from the patients with gastric adenocarcinoma. RESULTS: In gastric carcinoma cells, 53BP1 and gamma-H2AX were highly expressed as compared to normal epithelial cells and gastric adenoma (p<0.01). There were no differences in the expression of 53BP1 and gamma-H2AX between normal epithelium and gastric adenoma. The expression of 53BP1 in the adenoma with grade II and III atypism was more elevated than in those with grade I atypism. The expression of 53BP1 and gamma-H2AX were not significantly different according to the clinicopathologic parameters in the patients with gastric adenocarcinoma. CONCLUSIONS: The DSB in DNA seems to be associated with the development of gastric adenocarcinoma, but does not affect the premalignant adenoma cells.
Adenocarcinoma/genetics/*metabolism/secondary ; Adenoma/genetics/*metabolism/pathology ; Adult ; Aged ; Aged, 80 and over ; Chromosomal Instability ; *DNA Breaks, Double-Stranded ; Female ; Histones/metabolism ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; Male ; Middle Aged ; Neoplasm Staging ; Stomach Neoplasms/genetics/*metabolism/pathology

BACKGROUND: Uterine leiomyomas are common benign smooth muscle tumors among the reproductive aged-women. The research has been aimed to identify the differentially expressed genes between normal myometrium and leiomyoma and to investigate the effects of E2 on their expression. METHODS: Gene microarray analysis was performed to identify the differentially expressed genes between normal myomerium and leiomyoma. The data was confirmed at protein level by tissue microarray. RESULTS: Gene microarray analysis revealed 792 upregulated genes in leiomyoma. Four genes (tropomyosin 4 [TPM4], collagen, type IV, alpha 2 [COL4alpha2], insulin-like growth factor binding protein 5 [IGFBP5], tripartite motif-containing 28 [TRIM28]) showed the most dramatic upregulation in all leiomyoma samples. Tissue microarray analyses of 262 sample pairs showed significantly elevated expression of TPM4, IGFBP5, estrogen receptor-alpha, and progesterone receptor (PR) protein in leiomyoma from the patients in their forties, COL4alpha2 in the forties and fifties age-groups, and TRIM28 in the thirties age-group. PR, insulin-like growth factor 1 (IGF-1), IGF-1 receptor (IGF-1R) and IGFBP5 were induced by E2 in in vitro culture of tissue explants from which cells migrated throughout the plate. Among these, PR, IGF-1, IGFBP5 genes showed higher expression in tissue compared to cells-derived from tissue in leiomyoma and IGF-1R in leiomyoma cell. CONCLUSIONS: This observation implies the importance of the whole tissue context including the cells-derived from tissue in the research for the understanding of molecular mechanism of leiomyoma. Here, we report higher expression of TRIM28 in leiomyoma for the first time and identify E2-responsive genes that may have important roles in leiomyoma development.
Animals ; Collagen Type IV ; Estrogens ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Insulin-Like Growth Factor Binding Protein 5 ; Insulin-Like Growth Factor I ; Leiomyoma ; Mice ; Microarray Analysis ; Myometrium ; Oligonucleotide Array Sequence Analysis ; Receptor, IGF Type 1 ; Receptors, Progesterone ; Smooth Muscle Tumor ; Tissue Array Analysis ; Transcriptome ; Up-Regulation ; Uterus