Purpose: We aimed to identify the genetic causes of hypospadias in children using targeted gene panel sequencing for disorders of sex development (DSD). Materials and Methods: This study included 18 twin boys with hypospadias: seven and two pairs were monozygotic and dizygotic twins, respectively, and six were discordant and three were concordant twins. Targeted gene panel sequencing for 67 known DSD genes was performed. Sequence variants were classified into five different categories, pathogenic, likely pathogenic, variants of uncertain significance, likely benign, and benign, following the American College of Medical Genetics and Genomics Standards and Guidelines. Results: The mean gestational age and birth weight were 35.3±2.0 weeks and 1.96±0.61 kg, respectively, with seven patients being small for gestational age. Hypospadias was present in 12 patients, with posterior type in 33.3% and anterior type in 66.7%.In three families with twins, both siblings had hypospadias. In addition, cryptorchidism was observed in one subject. Surgical correction of hypospadias was performed at a mean age of 22.1 months. Molecular analysis identified 12 different genetic variants, including two pathogenic mutations in the AMH (p.E389*) and SRD5A2 (p.R246Q) genes, found in subjects with hypospadias, respectively. However, only heterozygous mutations were detected. Conclusions This study did not identify a definitive genetic component contributing to the development of hypospadias; however, the findings suggest that intrauterine growth retardation may play a significant role.

Purpose: To investigate growth response in children with either idiopathic short stature (ISS) or growth hormone (GH) deficiency (GHD). Methods: The data of prepubertal GHD or ISS children treated using recombinant human GH were obtained from the LG Growth Study database. GHD children were further divided into partial and complete GHD groups. Growth response and factors predicting growth response after 1 and 2 years of GH treatment were investigated. Results: This study included 692 children (98 with ISS, 443 partial GHD, and 151 complete GHD). After 1 year, changes in height standard deviation score (ΔHt-SDS) were 0.78, 0.83, and 0.96 in ISS, partial GHD, and complete GHD, respectively. Height velocity (HV) was 8.72, 9.04, and 9.52 cm/yr in ISS, partial GHD, and complete GHD, respectively. ΔHt-SDS and HV did not differ among the 3 groups. Higher initial body mass index standard deviation score (BMI-SDS) and midparental height standard deviation score (MPH-SDS) were predictors for better growth response after 1 year in ISS and the partial GHD group, respectively. In the complete GHD group, higher Ht-SDS and BMI-SDS predicted better growth response after 1 year. After 2 years of GH treatment, higher BMI-SDS and MPH-SDS predicted a better growth outcome in the partial GHD group, and higher MPH-SDS was a predictor of good growth response in complete GHD. Conclusion Clinical characteristics and growth response did not differ among groups. Predictors of growth response differed among the 3 groups, and even in the same group, a higher GH dose would be required when poor response is predicted.

We report a unique case of synchronous double primary gastric cancer consisting of adenocarcinoma components with micropapillary features and composite glandular-endocrine cell carcinoma components. The patient was a 53-year-old man presenting with a 6-month history of epigastric pain and diarrhea. A subtotal gastrectomy was performed. Histologically, one tumor was composed of micropapillary carcinoma components (50%) with tight clusters of micropapillary aggregates lying in the empty spaces, admixed with moderately differentiated adenocarcinoma components. MUC-1 was expressed at the stromal edge of the micropapillary component. The other tumor was composed of atypical carcinoid-like neuroendocrine carcinoma (50%), adenocarcinoid (30%), and adenocarcinoma components (20%). The neuroendocrine components were positive for CD56, synaptophysin, chromogranin, and creatine kinase. The adenocarcinoid components were positive for both carcinoembryonic antigen and neuroendocrine markers (amphicrine differentiation). This case is unique, due to the peculiar histologic micropapillary pattern and the histologic spectrum of adenocarcinoma adenocarcinoid-neuroendocrine carcinoma of the synchronous composite tumor.
Adenocarcinoma* ; Carcinoembryonic Antigen ; Carcinoma, Neuroendocrine ; Creatine Kinase ; Deception ; Diarrhea ; Gastrectomy ; Humans ; Middle Aged ; Stomach Neoplasms ; Stomach* ; Synaptophysin

PURPOSE: This study investigated the incidence trends and associated factors of type 1 (T1DM) and type 2 diabetes mellitus (T2DM) in children and adolescents under 15 years of age in Busan and Gyeongnam, Korea from 2001 to 2010. METHODS: Medical records of newly diagnosed diabetes patients (n=328; 160 males, 168 females) were collected in questionnaire form from 5 tertiary and 42 general hospitals in Busan and Gyeongnam. RESULTS: The average crude incidence rate of T1DM and T2DM was 2.01/100,000 (95% confidence interval [CI], 1.76-2.28) and 0.75/100,000 (95% CI, 0.60-0.92), respectively. The incidence rate ratio (IRR) of T1DM was 1.31 (95% CI, 1.01-1.69), and that of T2DM was 1.97 (95% CI, 1.25-3.11) in the latter half-decade (2006 to 2010) compared to the early half-decade (2001 to 2005). There were gradually increasing incidence trends in both T1DM and T2DM over the 10-year period (P for trend: T1DM, 0.0009; T2DM, <0.0001). Age-specific IRR was highest in the 10- to 14-year-old group, regardless of diabetes type. In particular, a rapid increase in incidence of T2DM occurred in the 10- to 14-year-old group. IRR for females was 1.07 (95% CI, 0.83-1.38) for T1DM and 1.56 (95% CI, 1.01-2.41) for T2DM. IRR for Busan (urban) was 1.41 (95% CI, 1.09-1.83) for T1DM and 1.49 (95% CI, 0.96-2.30) for T2DM. CONCLUSION: T1DM and T2DM incidence both increased over time in youth under age 15 living in Busan and Gyeongnam; in particular, the incidence of T2DM in adolescents increased more rapidly.
Adolescent* ; Busan* ; Child* ; Cohort Studies* ; Diabetes Mellitus* ; Diabetes Mellitus, Type 2 ; Female ; Hospitals, General ; Humans ; Incidence* ; Korea ; Male ; Medical Records ; Retrospective Studies*

PURPOSE: The 7th edition UICC/AJCC TNM classification for gastric cancer has several changes from the previous edition. Especially, the classification of the number of lymph node metastases (LNM) is reorganized. According to the new TNM system, N stage was categorized to N0 (no LNM), N1 (1~2 LNM), N2 (3~6 LNM), N3 (7 or more LNM). The aim of our study was to compare the prognostic significance of the new (7th) UICC/AJCC N stage with the old (6th). METHODS: From 2000 to 2005 a total of 425 patients who underwent curative resections with D2 and with 15 or more lymph nodes retrieved were studied retrospectively. RESULTS: According to the 7th UICC/AJCC N stage, the 5-year cumulative survival rates (5YSR) of N0, N1, N2, N3 were 96.0%, 79.2%, 58.5% and 24.3%, respectively (P<0.001). Using univariate analysis, the N stage of 7th and 6th UICC/AJCC TNM classification, 7th UICC/AJCC T stage, differentiation of tumor, type of gastrectomy (subtotal and total gastrectomy), size of primary tumor (< or =5, 5<< or =10, 10<) were associated with 5YSR. However, Cox regression multivariate analysis showed the 7th UICC/AJCC N stage to bean independent factor for predicting the 5YSR instead of the 6th UICC/AJCC N stage (P<0.001, hazard ratio (HR) 1.859, 95% confidence interval (CI) 1.576~2.194), including depth of tumor invasion (P<0.001, HR 1.673, 95% CI 1.351~2.073). CONCLUSION: The new (7th) UICC/AJCC N stage is a more reliable prognostic factor of gastric cancer than the old (6th) N stage.
Gastrectomy ; Humans ; Lymph Nodes ; Multivariate Analysis ; Neoplasm Metastasis ; Retrospective Studies ; Stomach Neoplasms ; Survival Rate

Head and neck surgeons see many congenital cysts of the neck. Most of these cysts are thyroglossal duct cysts and branchial cleft cysts. Bronchogenic cysts are rare congenital malformations of the ventral foregut development. They are usually located in the mediastinum and intrapulmonary regions. Cervical bronchogenic cysts are unusual. Only 70 cases of bronchogenic cysts in the head and neck regions have been reported on and the majority of cases have been found in the pediatric population. We describe here a 61-year-old female who presented a palpable left neck mass. The preoperative diagnostic studies included chest X-ray and sonography-guided fine needle aspiration. The neck sonography showed the mass, but it could not rule out a pathologic lymph node. Aspirated material contained no cellular content. The mass was excised. The neck mass of the patient was diagnosed as a bronchogenic cyst. We suggest that the clinical observation of a lateral neck mass in an adult includes the possibility of a bronchogenic cyst in the differential diagnosis.
Adult ; Biopsy, Fine-Needle ; Branchioma ; Bronchogenic Cyst* ; Diagnosis, Differential ; Female ; Head ; Humans ; Lymph Nodes ; Mediastinum ; Middle Aged ; Neck ; Thorax ; Thyroglossal Cyst

BACKGROUND: The aim of this study was to investigate the prevalence, clinical and laboratory findings of hereditary hemolytic anemia (HHA) in Korea from 1997 to 2006 and to develop the appropriate diagnostic approach for HHA. METHODS: By the use of questionnaires, information on the clinical and laboratory findings ofHHA diagnosed from 1997 to 2006 in Korea was collected and analyzed retrospectively. A total of 431 cases were enrolled in this study from 46 departments of 35 hospitals. RESULTS: The overall frequency of HHA did not change through the 10-year period for pediatrics but did show an increasing tendency for internal medicine. The overall male to female sex ratio did not show sex predominance (1.17:1), but a significant male predominance with a ratio of 1.49:1 was seen for pediatrics while a significant female predominance with a ratio of 1:1.97 was seen forinternal medicine. Of the total cases, 74.2% (282/431) were diagnosed before the age of 15 years. The etiologies of HHA were classified as red cell membrane defects, hemoglobinopathies, red cell enzyme deficiencies and unknown causes. There were 382 cases (88.6%) of red cell membrane defects with 376 cases (87.2%) of hereditary spherocytosis and 6 cases (1.4%) of hereditary elliptocytosis, 20 cases (4.6%) of hemoglobinopathies with 18 cases (4.2%) of beta-thalassemia, a case (0.2%) of alpha-thalassemia and a case (0.2%) of Hemoglobin Madrid, 7 cases (1.6%) of red cell enzyme deficiencies with 5 cases (1.2%) of glucose-6- phosphate dehydrogenase (G-6-PD) deficiency, a case (0.2%) of pyruvate kinase (PK) deficiency and a case (0.2%) of enolase deficiency, and 22 cases (5.1%) of unknown causes. The most common chief complaint in pediatric patients was pallor and that in adult patients was jaundice. In the red cell membrane defect group of patients, the level of hemoglobin was significantly higher than in adult patients. The mean corpuscular volume, mean corpuscular hemoglobin, corrected reticulocyte count, total and indirect bilirubin level and lactate dehydrogenase levels in the hemoglobinopathy group of patients were significantly lower than the values in the red cell membrane defect group of patients. The mean concentration of G-6-PD was 0.8+/-0.7U/1012RBC in the G-6-PD deficient patients, PK was 1.7U/1010 RBC in the PK deficient patient, and the level of enolase was 0.04U/g of Hb in the enolase deficient patient. CONCLUSION: The most prevalent cause of HHA in Korea during 1997 to 2006 was hereditary spherocytosis, but HHA by other causes such as hemoglobinopathy and red cell enzyme deficiency gradually increased with the development of molecular diagnostic methods and increasing general interest. However, the etiologies of HHA need to be pursued further in 5.1% of the patients. An systematic standard diagnostic approach is needed in a nationwide prospective study for correct diagnoses and appropriate management of HHA.
Adult ; alpha-Thalassemia ; Anemia, Hemolytic, Congenital* ; beta-Thalassemia ; Bilirubin ; Cell Membrane ; Diagnosis ; Elliptocytosis, Hereditary ; Erythrocyte Indices ; Female ; Hemoglobinopathies ; Humans ; Internal Medicine ; Jaundice ; Korea* ; L-Lactate Dehydrogenase ; Male ; Oxidoreductases ; Pallor ; Pathology, Molecular ; Pediatrics ; Phosphopyruvate Hydratase ; Prevalence ; Pyruvate Kinase ; Reticulocyte Count ; Retrospective Studies* ; Sex Ratio ; Surveys and Questionnaires

BACKGROUND: Deep hypothermic circulatory arrest during repair of aortic arch anomalies may induce neurological complications or myocardial injury. So we surveyed if the regional cerebral and myocardial perfusion might eliminate those potential side effects. MATERIAL AND METHOD: From March 2000 to December 2004, 62 neonates or infants with aortic arch anomaly underwent one stage biventricular repair using the regional perfusion technique by single surgeon. Preoperative diagnosis of the arch anomaly consisted of coarctation (n=46), interruption of the aorta (n=12), hypoplastic left heart syndrome (n=2) and truncus areteriosus (n=2). Combined anomalies were ventricular septal defect (n=51), TAPVR (n=1), PAPVR (n=1) and atrioventricular septal defect (n=2). Arterial cannula was inserted at the innominate artery. RESULT: The mean regional perfusion time of brain was 28+/-10 min. Operative mortality rates was 0 (0/62). Late death was 1 (1/62) during 11+/-7 months of follow-up. Neurologic complications consisted of transient chorea in 1 case. There was no reoperation associated with arch anolamy. Pulmonary complication associated with arch repair occurred in 1 case which was managed by aortopexy. CONCLUSION: One-stage arch repair using the regional prefusion is safe and effective in minimizing the neurologic and myocardial complications.
Aorta ; Aorta, Thoracic* ; Brachiocephalic Trunk ; Brain ; Catheters ; Chorea ; Circulatory Arrest, Deep Hypothermia Induced ; Diagnosis ; Follow-Up Studies ; Heart Septal Defects, Ventricular ; Humans ; Hypoplastic Left Heart Syndrome ; Hypothermia ; Infant ; Infant, Newborn ; Mortality ; Perfusion* ; Regional Blood Flow ; Reoperation ; Scimitar Syndrome

PURPOSE: To obtain phVEGF165 for angiogenesis and to compare the effects of its intra-arterial and intramuscular administration in a chronic ischemic rabbit hindimb model. MATERIALS AND METHODS: Chronic ischemic models were constructed in the left hindlimb of rabbits and divided into control (n=6), intra-arterial (n=7) and intramuscular groups (n=5). Plasmid DNA (phVEGF165) expressing vascular endothelial growth factor (VEGF) was obtained from HL60 cells, and transfection into CHO cells and western blot analysis of the medium, as well as proliferation assay of CPAE cells were performed. Two weeks after construction of the models, 500 mug phVEGF165 was injected into both the left common iliac artery and thigh muscles. Angiography was performed and the number of vessels counted, and ELISA was used to determine the quantity of VEGF in blood samples. Wilcoxon signed rank test was employed for statistical analysis. RESULTS: VEGF165 was expressed on western blot of the culture medium. Proliferation assay showed that optical densities were 0.73+/-0.043 in the control study and 1.09+/-0.015 in phVEGF165. The angiographic scores were 1.32+/-0.13 (pre-gene therapy) and 1.30+/-0.07 (post-gene therapy) in the control group, 1.42+/-0.15 and 1.59+/-0.09 in the intra-arterial group, 1.59+/-0.27 and 1.14+/-0.12 in the intramuscular group. The differences were not statistically significant. In the intra-arterial group, serum VEGF levels were 39.96+/-1.08 pg/ml (pregene therapy), 44.99+/-2.13 pg/ml (4th day), 48.18+/-1.49 pg/ml (1st week), 45.70+/-3.77 pg/ml (2nd week), and 46.54+/-5.47 pg/ml (3rd week), but in the control and intramuscular groups there were no increases. CONCLUSION: phVEGF165 affected the proliferation of CPAE cells. There was no difference in angiographic scores and serum VEGF levels between intra-arterial and intramuscular administrations.
Angiography ; Animals ; Blotting, Western ; CHO Cells ; Cricetinae ; DNA ; Enzyme-Linked Immunosorbent Assay ; Genetic Therapy ; Hindlimb* ; HL-60 Cells ; Humans ; Iliac Artery ; Muscles ; Plasmids ; Rabbits ; Thigh ; Transfection ; Vascular Endothelial Growth Factor A

BACKGROUND: The expression of the multidrug resistance-1 (MDR-1) gene which encodes p-glycoprotein, is recognized as a biological mechanism possibly contributing to treatment failure in patients with acute myeloid leukemia (AML). Recent studies indicate its association with poor risk factors such as cytogenetic pattern and surface phenotype of blasts. We analyzed the role of MDR-1 gene expression in 36 chemo-naive AML patients. METHODS: In 36 patients, clinical data were reviewed and compared to MDR-1 gene expression, immunophenotyping results on CD7 & CD34, cytogenetic pattern and other suggestive prognostic factors. RESULTS: Median follow-up period was 150 days. The MDR-1 gene expression was observed in 19 out of 36 patients (52.8%). Significant correlation between MDR-1 gene and CD7 & CD34 expression was found. Sixteen out of 17 (94.1%) MDR-1 negative patients harbored favorable cytogenetic patterns, where as 11 out of 19 (57.9%) MDR-1 positive patients had favorable cytogenetic patterns. MDR-1 gene expression was not correlated to disease free survival (DFS), nor overall survival (OS) statistically although it has shown significant correlation to complete remission (CR) rate (P =0.001). CONCLUSION: We found that lack of MDR-1 gene expression was exclusively associated to favorable cytogenetic patterns in our study. In order to clarify the relationship between the role of MDR-1 gene and clinical outcome or other prognostic features, including cytogenetic pattern, further larger studies would be necessary.
Cytogenetics ; Disease-Free Survival ; Follow-Up Studies ; Gene Expression* ; Humans ; Immunophenotyping ; Leukemia, Myeloid, Acute* ; P-Glycoprotein ; Phenotype ; Risk Factors ; Treatment Failure