Site-specific cancer risk in patients with type 2 diabetes: a nationwide population-based cohort study in Korea

Background/Aims@#We aimed to evaluate site-specific cancer risk in diabetic patients and to investigate causal and temporal relationships by analyzing organ-specific cancer risk according to the duration of diabetes. @*Methods@#Using a database provided by the Korean National Health Insurance Service, we conducted a retrospective, population-based cohort study of adults aged ≥ 30 years from January 2005 to December 2013. To verify the possibility of detection bias or reverse causation, we compared hazard ratios (HRs) for each cancer according to the following duration of diabetes: less than 6 months, 6 months to 3 years, and more than 3 years. @*Results@#The incidence of overall cancer per 1,000 person-years was higher in patients with diabetes than in those without diabetes (20.36 vs. 10.83). The overall cancer risk according to the duration of diabetes was the highest within the first 6 months after diagnosis (HR, 2.03; 95% confidence interval [CI], 1.99 to 2.07), and the HR decreased with the duration of diabetes, ranging from 1.19 (95% CI, 1.18 to 1.21) between 6 months and 3 years to 1.12 (95% CI, 1.11 to 1.13) after 3 years. Both overall cancer risk and HR remained significantly higher in patients with diabetes than in those without diabetes. The risk for prostate cancer was higher in men with diabetes than in those without diabetes (HR, 1.12; 95% CI, 1.10 to 1.14). In women, the risk for endometrial cancer was significantly higher in patients with diabetes than in those without diabetes throughout the duration of diabetes. @*Conclusions@#The risk for stomach, colorectum, liver, pancreas, and kidney cancer appeared to be higher in patients with diabetes than in those without diabetes regardless of the sex or duration of diabetes.

Impaired Cortisol and Growth Hormone Counterregulatory Responses among Severe Hypoglycemic Patients with Type 2 Diabetes Mellitus

BACKGROUND: Elevated levels of cortisol and growth hormone are critical counterregulatory responses to severe hypoglycemia. However, the proportion and clinical characteristics of patients with type 2 diabetes mellitus (DM) who fail to show appropriate cortisol and/or growth hormone secretion in response to severe hypoglycemia have not been investigated. METHODS: We measured plasma cortisol and growth hormone levels in type 2 DM patients with severe hypoglycemia who visited the emergency department between 2006 and 2015. RESULTS: Of 112 hypoglycemic patients, 23 (20.5%) had an impaired cortisol response (<18 µg/dL) and 82 patients (73.2%) had an impaired growth hormone response (<5 ng/mL). Nineteen patients (17.0%) had impaired responses to both cortisol and growth hormone. The patients with impaired responses of cortisol, growth hormone, and both hormones were significantly older and more likely to be female, and had higher admission rates, lower growth hormone levels, and lower adrenocorticotropic hormone levels than the patients with a normal hormonal response. Multivariate logistic regression analysis indicated that an impaired growth hormone response was significantly associated with advanced age, shorter DM duration, a higher admission rate, and a higher body mass index (BMI). An impaired cortisol response was significantly associated with growth hormone levels. Patients with an impaired growth hormone response had higher admission rates than patients with a normal response. CONCLUSION: A considerable number of type 2 DM patients had impaired cortisol and/or growth hormone responses to severe hypoglycemia. Advanced age, shorter DM duration, and higher BMI were independently associated with an abnormal growth hormone response.

Higher Morbidity of Monogenic Inflammatory Bowel Disease Compared to the Adolescent Onset Inflammatory Bowel Disease / 대한소아소화기영양학회지

PURPOSE: Monogenic inflammatory bowel disease (IBD) patients do not respond to conventional therapy and are associated with a higher morbidity. We summarized the clinical characteristics of monogenic IBD patients and compared their clinical outcomes to that of non-monogenic IBD patients. METHODS: We performed a retrospective cohort study of all children <18 years old who were diagnosed with IBD between 2005 and 2016. A total of 230 children were enrolled. Monogenic IBD was defined as a presentation age less than 6 years old with confirmation of a genetic disorder. We subdivided the groups into monogenic IBD (n=18), non-monogenic very early-onset IBD (defined as patients with a presentation age <6 years old without a confirmed genetic disorder, n=12), non-monogenic IBD (defined as all patients under 18 years old excluding monogenic IBD, n=212), and severe IBD (defined as patients treated with an anti-tumor necrosis factor excluding monogenic IBD, n=92). We compared demographic data, initial pediatric Crohn disease activity index/pediatric ulcerative colitis activity index (PCDAI/PUCAI) score, frequency of hospitalizations, surgical experiences, and height and weight under 3rd percentile among the patients enrolled. RESULTS: The initial PCDAI/PUCAI score (p < 0.05), incidence of surgery per year (p < 0.05), and hospitalization per year (p < 0.05) were higher in the monogenic IBD group than in the other IBD groups. Additionally, the proportion of children whose weight and height were less than the 3rd percentile (p < 0.05 and p < 0.05, respectively) was also higher in the monogenic IBD group. CONCLUSION: Monogenic IBD showed more severe clinical manifestations than the other groups.

Peripheral Eosinophilia and Clinico-radiological Characteristics among Health Screening Program Recipients / 결핵및호흡기질환

BACKGROUND: Eosinophilia is well recognized in specific conditions. The objective of the present study was to determine clinico-radiologic characteristics of eosinophilia and changes in prevalence over 10 years in recipients of private health screening program at a tertiary hospital in Korea. METHODS: Data of private health screening program recipients at the health promotion center of Chung-Ang University Hospital from 2004 to 2013 were collected. Health-related questionnaires and laboratory findings of private health screening program with possible relation with eosinophilia were reviewed. Results of enzyme-linked immunosorbent assay (ELISA) for parasite, chest computed tomography, and pulmonary function test were also reviewed. RESULTS: The cumulative prevalence of eosinophilia was 4.0% (1,963 of 48,928). Prevalence of eosinophilia showed a decreased trend from 2004 to 2013. Most cases (96.6%) had mild degree of eosinophilia. Eosinophilic subjects were older and male-predominant. They showed lower levels of forced expiratory volume in 1 second (FEV₁%), forced vital capacity (FVC%), and FEV₁/FVC than those without eosinophilia. Eosinophilic subjects showed higher positive rate for common parasite in ELISA than those without eosinophilia. On radiologic findings, consolidation and ground glass opacities were positively associated with the degree of eosinophilia. When eosinophil was classified based on severity, statistically significant correlation between the severity of eosinophil and radiologic abnormalities was found. CONCLUSION: Eosinophilia is uncommon in healthy population. It usually occurs at a mild degree. Eosinophilic patients have more radiologic abnormalities compared to those without eosinophilia. Such radiologic abnormalities are associated with the severity of eosinophilia.

Effect of the Baseline Vitamin D Level on Growth Outcome in Pediatric Crohn Disease / 대한소아소화기영양학회지

PURPOSE: Vitamin D deficiency is common in Crohn disease (CD). The aim of the study was to examine the prevalence of vitamin D deficiency and evaluate the association between vitamin D status and growth outcome in Korean pediatric CD patients. METHODS: In this retrospective study, 17 children younger than 18 years old diagnosed with CD were enrolled and their serum 25-hydroxy vitamin D (25[OH]D) was checked between 2011 and 2015. We categorized the patients into two groups, Group 1 and Group 2. Group 1 included patients with serum 25(OH)D levels below 10 ng/mL, and Group 2 was for patients with a 25(OH)D serum levels between 10 ng/mL and 30 ng/mL. The z-scores for height (Htz), weight (Wtz), and body mass index (BMIz) were measured at baseline, 6 months, and 12 months. RESULTS: The mean serum 25(OH)D levels of the total 65 CD patients and 17 enrolled patients were 15.64±6.9 ng/mL and 13.1±5.1 ng/mL, respectively. There was no correlation at the beginning of the study between vitamin D level and growth parameters (Htz, Wtz, BMIz) or other variables including laboratory data and Pediatric Crohn Disease Activity Index. The Htz, Wtz, and BMIz in Group 1 showed no significant improvement at 6 months and 12 months follow-up. In Group 2, Wtz and BMIz showed significant improvements sustained until 12 months of follow-up. Htz showed no significant improvement at 6 months but there was significant improvement at 12 months. CONCLUSION: It seems that baseline vitamin D status affects growth outcome in pediatric CD.

Selenium Concentration in Korean Patients with Thyroid Disease: a Preliminary Report

BACKGROUND AND OBJECTIVES: Selenium is an important trace element for thyroid hormone metabolism, and its deficiency can cause hypothyroidism. Serum selenium concentration is the best biomarker to reflect selenium intake and reserve, although other markers can reflect. Therefore, we preliminarily assessed serum and urine selenium concentrations in patients with thyroid disease compared to those of a healthy population. We also investigated the correlation between serum and urine selenium concentration, thyroid hormone and urinary iodine concentration (UIC). MATERIALS AND METHODS: A total of 97 patients (32 men, 65 women, 52.4±14.7 years) with benign thyroid nodules or thyroid dysfunction who visited the Samsung Medical Center between 2008 and 2013 were included. Data for 175 healthy subjects provided by Lee et al. were used as the control. Serum T3, free T4, and thyroid stimulating hormone (TSH) were measured using commercialized RIA or IRMA kits. Serum/urine selenium and UIC were measured by inductively coupled plasma-mass spectrometry (ICP-MS). RESULTS: Median serum selenium concentration was 110 µg/L (95% CI, 73-156). Median urine selenium concentration was 66.3 µg/gCr (95% CI, 28.7-283.5). Compared to 175 healthy subjects (serum 84 µg/L [95% CI, 30-144], urine 34.5 µg/gCr [95% CI, 0.8-107.2]), serum and urine selenium concentrations of patients with thyroid disease were significantly higher than those of healthy subjects (p<0.001). Serum selenium concentration was significantly correlated with urine selenium concentration after log transformation (r=0.88, p=0.022), but was not significantly correlated with UIC, T3, free T4 and TSH. CONCLUSION: Selenium concentrations of patients with thyroid disease were significantly higher than those of healthy subjects. Serum selenium concentration was significantly correlated with urine selenium concentration.

Selenium Concentration in Korean Patients with Thyroid Disease: a Preliminary Report

BACKGROUND AND OBJECTIVES: Selenium is an important trace element for thyroid hormone metabolism, and its deficiency can cause hypothyroidism. Serum selenium concentration is the best biomarker to reflect selenium intake and reserve, although other markers can reflect. Therefore, we preliminarily assessed serum and urine selenium concentrations in patients with thyroid disease compared to those of a healthy population. We also investigated the correlation between serum and urine selenium concentration, thyroid hormone and urinary iodine concentration (UIC). MATERIALS AND METHODS: A total of 97 patients (32 men, 65 women, 52.4±14.7 years) with benign thyroid nodules or thyroid dysfunction who visited the Samsung Medical Center between 2008 and 2013 were included. Data for 175 healthy subjects provided by Lee et al. were used as the control. Serum T3, free T4, and thyroid stimulating hormone (TSH) were measured using commercialized RIA or IRMA kits. Serum/urine selenium and UIC were measured by inductively coupled plasma-mass spectrometry (ICP-MS). RESULTS: Median serum selenium concentration was 110 µg/L (95% CI, 73-156). Median urine selenium concentration was 66.3 µg/gCr (95% CI, 28.7-283.5). Compared to 175 healthy subjects (serum 84 µg/L [95% CI, 30-144], urine 34.5 µg/gCr [95% CI, 0.8-107.2]), serum and urine selenium concentrations of patients with thyroid disease were significantly higher than those of healthy subjects (p<0.001). Serum selenium concentration was significantly correlated with urine selenium concentration after log transformation (r=0.88, p=0.022), but was not significantly correlated with UIC, T3, free T4 and TSH. CONCLUSION: Selenium concentrations of patients with thyroid disease were significantly higher than those of healthy subjects. Serum selenium concentration was significantly correlated with urine selenium concentration.

Seven-Day Continuous Abstinence Rate from Smoking at 1, 2, or 3 Years after the Use of Varenicline / 결핵및호흡기질환

BACKGROUND: Varenicline, a selective partial agonist/antagonist of the alpha4beta2 nicotinic receptor, has proven effectiveness for smoking cessation by several randomized, controlled trials. Because few studies have evaluated the long-term efficacy of varenicline, we tried to evaluate the smoking status of varenicline users up to 3 years after the initial prescription of the drug. METHODS: We interviewed varenicline users who were prescribed the drug from June 2007 to May 2010 by telephone, from June 2010 to May 2011. RESULTS: One-hundred and thirty-three of 250 varenicline users (53.2%) were available for the survey. Seven-day continuous abstinence from smoking was adhered to by 17 of 39 respondents (43.6%) at 1 year, and 11 of 36 (30.6%) and 19 of 58 (32.8%) at 2 and 3 years since the first use of varenicline, respectively. Compared to current smokers, successful quitters were older (55.0 years vs. 49.9 years, p=0.01), had better compliance to the 12-week course (27.7 vs. 9.3%, p=0.01), and had taken varenicline longer (10.1 vs. 5.9 weeks, p=0.01). Fifty-four of 71 current smokers (76.1%) were willing to stop smoking in the near future. The preferred ways to cease smoking were will-power (48.1%), varenicline (25.9%), nicotine replacement therapy (11.1%), and others (14.9%). CONCLUSION: Smokers should be encouraged to stick to the proven way for recommended period of time for successful cessation of smoking.

Acute Eosinophilic Pneumonia Leading to Acute Respiratory Failure in a Current Systemic Corticosteroid User

A 69-year-old female patient visited the emergency room with fever (38.3degrees C) and dyspnea. She had been taking prednisolone (5 mg once per day) and methotrexate (2.5 mg once per week) for rheumatoid arthritis for 2 years. Chest computed tomography (CT) showed bilateral, multifocal ground glass opacity with interlobular septal thickening. Peripheral blood leukocyte count was 6,520/mm3 (neutrophils, 77.4%; eosinophils, 12.1%). During the night, mechanical ventilation was initiated due to the development of severe hypoxemia. Bronchoalveolar lavage fluid showed a high proportion of eosinophils (49%). Her symptoms improved dramatically after commencement of intravenous methylprednisolone therapy. This is the first report of idiopathic acute eosinophilic pneumonia developing in a current user of systemic corticosteroids.

A Case of Giant, Benign Schwannoma Associated with Total Lung Collapse by Bloody Effusion / 결핵및호흡기질환

Benign schwannoma is the most common neurogenic tumor in the mediastinum. Mediastinal benign schwannomas are most often asymptomatic and rarely accompanied by bloody pleural effusion. In the clinical analysis of 7 cases of pulmonary schwannomas, pleural effusion, and blood invasion were evident in 3 patients with malignant schwannoma. Herein, we report a rare case of giant, benign schwannoma presented with total collapse of right lung by massive, bloody pleural effusion.

Four Year Trend of Carbapenem-Resistance in Newly Opened ICUs of a University-Affiliated Hospital of South Korea / 결핵및호흡기질환

BACKGROUND: Carbapenem-resistance is rapidly evolving among the pathogenic microbes in intensive care units (ICUs). This study aimed to determine annual trend of carbapenem-resistance in the ICU for 4 years, since the opening of a university-affiliated hospital in South Korea. METHODS: From 2005 to 2008, microbial samples from consecutive 6,772 patients were screened in the ICU. Three hundred and ninety-seven patients (5.9%) and their first isolates of carbapenem-resistant pathogens were analyzed. RESULTS: The percentage of patients infected with carbapenem-resistant organisms increased constantly during the initial three years (2.3% in 2005, 6.2% in 2006, 7.8% in 2007), then it declined to 6.5% in 2008. Acute Physiology and Chronic Health Evaluation (APACHE) III score at admission was 58.0+/-23.5, the median length of the ICU stay was 37 days, and the mortality rate was 37.5%. The sampling sites were endotracheal suction (67%), catheterized urine (17%), wound (6%) and others (10%). Bacteria with carbapenem-resistance were Pseudomonas aeruginosa (247 isolates, 62%), Acinetobacter baumannii (117 isolates, 30%), Enterobacteriaceae (12 isolates, 3%), and others (21, 5%). Of note, peak isolation of carbapenem-resistant microorganisms in medical ICU was followed by the same epidemic at surgical ICU. CONCLUSION: Taken together, carbapenem-resistant pathogens are of growing concern in the ICU.

Tumor Necrosis Factor-alpha Gene Polymorphisms in Korean Children with Inflammatory Bowel Disease / 대한소아소화기영양학회지

PURPOSE: The aim of this study was to investigate the existence of TNF-alpha polymorphisms in Korean children with Crohn's disease (CD), ulcerative colitis (UC), as compared to healthy controls. METHODS: Blood samples were obtained from 40 patients with CD, 14 patients with UC, and 30 healthy controls. Genotyping for 5 TNF-alpha polymorphisms (G238A, G308A, C857T, C863A, and T1031C) was performed. The allele frequencies for the inflammatory bowel diseases, CD and UC, were measured in patients with these disease and in healthy controls, and these allele frequencies were compared between the 3 groups. We examined the significant association between polymorphism and disease phenotype, such as location, behavior, perianal disease, and pediatric Crohn's activity index (PCDAI) in CD. RESULTS: Based on our findings, the TNF-alpha allele frequencies of G238A, G308A, C857T, C863A, and T1031C were 3.3, 8.3, 16.7, 16.7, 21.7% in healthy control, 2.5%, 7.5%, 18.8%, 20.0%, 22.5% in CD, 7.1%, 7.1%, 7.1%, 21.4%, 28.6% in UC. They were no statistically significant differences between the 3 groups. There were no associations between genotypes and phenotypes in CD, except a statistically significant higher allele frequency of G238A in ileal type (L1) disease (p=0.010). CONCLUSION: Our results indicate that 5 TNF-alpha polymorphisms do not seem to be associated with susceptibility to inflammatory bowel disease in Korean pediatric patients even though young patients were anticipated to have a stronger genetic affiliation for these diseases than adult patients. We think that further studies are needed to find those genes associated with susceptibility to CD and UC in Korean pediatric patients with inflammatory bowel disease.

A Case of Antiphospholipid Syndrome Presenting as Pulmonary Infarction and Multiple Arterial Thromboembolism / 소아알레르기및호흡기학회지

Antiphospholipid syndrome (APS) is a noninflammatory autoimmune disorder characterized by the association of arterial and/or venous thrombosis, recurrent fetal loss and elevated titres of antiphospholipid antibodies, namely lupus anticoagulant (LAC) and/or anticardiolipin antibodies (aCL). It can either occur as a free-standing condition (primary APS) or be associated with another autoimmune disease (secondary APS), mainly systemic lupus erythematosus. The precise pathogenesis of thrombosis in APS in unknown. For children with unexplainable venous or arterial thrombosis, APS should be considered. The diagnosis of APS in children requires a clinical event including venous or arterial thrombosis or immune thrombocytopenia and a laboratory abnormality including positive LAC test or positive aCL antibody test, moderate or high titer IgG. The laboratory abnormality should persist for at least 2 months. We report a 7-year-old girl who had pulmonary embolism and multiple arterial thrombosis caused by primary APS. The laboratory abnormality was positive LAC and beta2-glycoprotein I. She was treated successfully with low molecualr weight heparin (LMWH). After recovery, she was continuously treated with subcutaneous LMWH for another 3 months and switched to oral warfarin. She was symptom-free through 3 years of follow-up.

Airway Expandible Metallic Stent Implantation in Children with Tracheal or Bronchial Stenosis / 소아과

PURPOSE: In adults, endoscopic tracheobronchial balloon dilatation and stenting have become valuable methods to establish and maintain an adequate airway lumen when tracheomalacia or neoplastic growth compromise the airways. But in children, only a few cases were reported due to technical problems. We report six children who were treated with stent implantation and describe the use and safety of airway stents. METHODS: Six patients with severe airway obstruction were treated. We investigated the underlying medical problems, stenotic site, symptomatic improvement and complications, and the size and location of stent. RESULTS: The median age of the six patients was 21 months. Three of them were mechanically ventilated and one had an endotracheal tube to maintain the patency of airway. Diagnoses were:congenital tracheal stenosis with or without bronchomalacia, granulation tissue formation after right upper lobectomy by bronchial carcinoid or after prolonged intubation, endobronchial tuberculosis, and airway compression by mediastinal undifferentiated sarcoma. Nitinol stents were implanted in the airway guided by bronchoscopy and fluoroscopy simultaneously. Three cases were placed in trachea, the others were in the bronchus. After stent implantation, all patients showed marked improvements of their airway obstructive symptoms. Four patients are doing well, although two expired due to underlying diseases. Four patients had granulation tissue formation around stents, but that was tolerable after removing the stent. CONCLUSION: We suggest that the use of expandible metallic stent implantation can offer safe therapeutic option even in extremely severe, life threatening and inoperable airway stenosis in children.

Familial Interstitial Lung Disease in Two Young Korean Sisters

Most of the interstitial lung diseases are rare, chronic, progressive and fatal disorders, especially in familial form. The etiology of the majority of interstitial lung disease is still unknown. Host susceptibility, genetic and environmental factors may influence clinical expression of each disease. With familial interstitial lung diseases, mutations of surfactant protein B and surfactant protein C or other additional genetic mechanisms (e.g. mutation of the gene for ATP-binding cassette transporter A3) could be associated. We found a 21 month-old girl with respiratory symptoms, abnormal radiographic findings and abnormal open lung biopsy findings compatible with nonspecific interstitial pneumonitis that is similar to those of her older sister died from this disease. We performed genetic studies of the patient and her parents, but we could not find any mutation in our case. High-dose intravenous methylprednisolone and oral hydroxychloroquine were administered and she is still alive without progression during 21 months of follow-up.

A Case of Posttransplant Lymphoproliferative Disease (PTLD) Following Renal Transplantation in a Child

Posttransplant lymphoproliferative disease (PTLD) represents a diverse lymphoproliferative disorder ranging from nonspecific reactive hyperplasia to malignant immunoblastic sarcoma developed in a setting of immunosuppression following organ or cellular transplantation. It is often associated with Epstein-Barr virus (EBV) infection and high dose immunosuppression. PTLD after renal transplantation was reported at first in adult in Korea in 1997. In children there have been several cases of PTLD after liver transplantation but PTLD after renal transplantation has not been reported. This is a case report of PTLD developed 4 months after renal transplantation in a 9-year-old boy. The major clinical manifestations were fever, multiple lymph nodes enlargement and blood-tinged stool. EBV was detected by in-situ hybridization in the enlarged cervical lymph node and the colonic tissue. Histological examination revealed B-cell lineage. Use of ganciclovir and reduction of the immunosuppression level resulted in complete remission of PTLD. This is the first pediatric case report of PTLD following renal transplantation in Korea.

Congenital Esophageal Stenosis: with Special Reference to Diagnosis and Postoperative Complications

PURPOSE: Congenital esophageal stenosis(CES) is one of the rare causes of recurrent vomiting during infancy and childhood. We studied the diagnostic and therapeutic tools and postoperative complications for early diagnosis and adequate management of CES. METHODS: Fourteen cases of CES were evaluated for clinical manifestations, findings of esophagogram and esophagoscopy, classification of pathologic findings and postoperative complications. RESULTS: Most common clinical manifestations at onset were non-projectile vomiting(14), dysphagia to solids(13). Age at onset of symptoms corresponded with the introduction of solids in 11 cases. Esophagogram showed segmental stenosis of variable length in the lower portion of the esophagus in all cases with marked proximal dilatation in 11 cases. Esophagoscopy revealed no signs of esophagitis or ulcer at the area of stenosis. Segmental resection and primary anastomosis were performed as a definitive treatment modality in all cases except one with fibromuscular stenosis. Bronchial cartilage were present in all cases of tracheobronchial remnants(10). Abnormal arrangement and thickening of muscularis mucosae and inner circular muscle were found in all cases of fibromuscular stenosis(4). Postoperative complications were gastroesophageal reflux(5), stricture of anastomotic sites, reflux esophagitis, and so on. CONCLUSION: CES is rare but should be considered as a cause of recurrent vomiting and dysphagia to solid food beginning in infancy and childhood especially in the weaning period. Esophagogram and esophagoscopy are useful tools for diagnosis and differential diagnosis. The stricture of anastomosis site, gastroesophageal reflux and esophagitis need to be evaluated in the follow-up postoperative periods.