Shyang-Rong Shih

Thyroid Segmentation and Volume Estimation in Ultrasound Images

The objective of this paper is to provide a complete solution to estimate the volume of the thyroid gland directly from US images. In this paper, the radial basis function (RBF) neural network is used to classify blocks of the thyroid gland; the integral region is further acquired by applying a specific region growing method to potential points. The parameters for evaluating the thyroid volume is estimated by a particle swarm optimization (PSO) algorithm. Experimental results of the thyroid region segmentation and volume estimation in US images show high potential of our proposed approach.

Serum Vascular Adhesion Protein-1 Predicts 10-Year Cardiovascular and Cancer Mortality in Individuals With Type 2 Diabetes

OBJECTIVE Vascular adhesion protein-1 (VAP-1) participates in inflammation and catalyzes the breakdown of amines to produce aldehyde, hydrogen peroxide, and ammonia. Serum VAP-1 correlates positively with both acute hyperglycemia and diabetes. We conducted a cohort study to evaluate whether serum VAP-1 predicts 10-year survival in type 2 diabetic patients. RESEARCH DESIGN AND METHODS Between July 1996 and June 2003, we enrolled 661 type 2 diabetic subjects at National Taiwan University Hospital. Serum VAP-1 in the samples obtained at enrollment was measured by time-resolved immunofluorometric assay. The vital status of all subjects was ascertained by linking their data with computerized death certificates in Taiwan. RESULTS The medium follow-up period was 10.4 years. Subjects with serum VAP-1 in the highest tertile had a hazard ratio (HR) of 2.19 (95% CI 1.17–4.11) for all-cause mortality adjusted for age, sex, smoking, history of cardiovascular disease, obesity, hypertension, hemoglobin A1c, diabetes duration, total cholesterol, use of statins, abnormal ankle-brachial index, estimated glomerular filtration rate (eGFR), and proteinuria. The adjusted HRs for logarithmically transformed serum VAP-1 were 5.83 (95% CI 1.17–28.97) for cardiovascular mortality, 6.32 (95% CI 1.25–32.00) for mortality from cardiovascular and diabetic causes, and 17.24 (95% CI 4.57–65.07) for cancer mortality. There were four variables, including age, serum VAP-1, proteinuria, and eGFR, which could enhance mortality prediction significantly. CONCLUSIONS Serum VAP-1 can predict 10-year all-cause mortality, cardiovascular mortality, and cancer mortality independently in type 2 diabetic subjects. Serum VAP-1 is a novel biomarker that improves risk prediction over and above established risk factors.

Serum vascular adhesion protein-1 is increased in acute and chronic hyperglycemia

BACKGROUND The relationship between serum vascular adhesion protein-1 (VAP-1) and plasma glucose in normal and drug-naïve type 2 diabetes subjects is unclear. We examined if serum VAP-1 changed acutely to oral glucose loading and analyzed the relationship between serum VAP-1, fasting plasma glucose (FPG), hemoglobin A1c, and type 2 diabetes. METHODS Adults without history of diabetes were included. Subjects taking anti-diabetic drugs were excluded. Serum VAP-1 was analyzed by time-resolved immunofluorometric assay. RESULTS We recruited 333 subjects (186 females and 147 males), aged 56.1 +/- 11.6 y. After glucose challenge, serum VAP-1 rose significantly at 30 min (p < 0.0001) and lasted until 2 h (p < 0.0001). The change of serum VAP-1 between fasting and 30-min postload correlated inversely to the change of plasma insulin (r = -0.21, p = 0.049). Fasting serum VAP-1 was associated with FPG in those with FPG > or = 5.55 mmol/l (p = 0.025) but not in those with FPG < 5.55 mmol/l (p = NS). Fasting serum VAP-1 were higher in diabetic subjects (p = 0.04) and correlated positively to hemoglobin A1c (r = 0.18, p = 0.002) after adjusting for age, gender, and waist circumference. CONCLUSIONS Serum VAP-1 is increased in both acute and chronic hyperglycemia. Whether serum VAP-1 is a good biomarker for hyperglycemia-associated complications merits further investigation.

Serum vascular adhesion protein-1 is higher in subjects with early stages of chronic kidney disease

OBJECTIVES An increased level of serum vascular adhesion protein-1 (VAP-1) has been found in patients with diabetes mellitus and vascular disorders. This study examined whether serum VAP-1 levels are associated with chronic kidney disease (CKD). DESIGN AND METHODS We included 262 subjects aged 30 and above with fasting plasma glucose level <7 mmol/L checked within 1 year. First morning urine specimens were collected. Microalbuminuria was defined if urinary albumin-to-creatinine ratio > or =30 microg/mg creatinine. The glomerular filtration rate (GFR) was estimated. CKD stages were defined according to the suggestions of the National Kidney Foundation. Serum VAP-1 levels were analyzed by immunofluorometric assay. RESULTS Serum VAP-1 levels were positively associated with the urinary albumin-to-creatinine ratio (r=0.29, p<0.0001) and negatively associated with estimated GFR (r=-0.24, p=0.0001). Subjects with CKD stage 2 (N=51) and stage 3 (N=91) had significantly higher levels of serum VAP-1 than those without CKD (p=0.0003 and p=0.035, adjusted for age and gender, respectively). A high serum VAP-1 level was associated with the presence of CKD (OR 1.63 for 1 SD increase of VAP-1, p=0.018), adjusting for age, sex, and smoking. Ordered logit models revealed that high serum VAP-1 levels correlated with advanced stages of CKD. CONCLUSIONS Serum levels of VAP-1 are associated with the severity of kidney damage or stages of kidney disease. The true mechanism which links the serum VAP-1 and CKD remains to be elucidated in further studies.

Reversal of myocardial fibrosis in patients with unilateral hyperaldosteronism receiving adrenalectomy

BACKGROUND Primary aldosteronism is the most frequent cause of secondary hypertension and is associated with more prominent left ventricular hypertrophy and increased myocardial fibrosis. Unilateral hyperaldosteronism can be cured by adrenalectomy. However, the reversibility of cardiac fibrosis is still unclear. METHODS We analyzed 11 patients prospectively with unilateral hyperaldosteronism (including 10 aldosterone-producing adenomas and 1 unilateral nodular hyperplasia) who received adrenalectomy from October 2006 to October 2007, and 17 patients with essential hypertension (EH) were enrolled as the control group. Echocardiography included ultrasonic tissue characterization by cyclic variation of integrated backscatter; it was performed in both groups and 1 year after operation in the unilateral hyperaldosteronism group. RESULTS Patients with unilateral hyperaldosteronism had significantly higher diastolic blood pressure, higher plasma aldosterone concentration, lower serum potassium level, and lower plasma renin activity than patients with EH. In echocardiography, patients with unilateral hyperaldosteronism had thicker interventricular septal thickness, left ventricular posterior wall thickness, and higher left ventricular mass index than EH patients. Patients with unilateral hyperaldosteronism had significant lower cyclic variation of integrated backscatter than EH patients (7.1 ± 2.1 vs 8.7 ± 1.5 dB, P = .037). After analyzing the correlation of cyclic variation of integrated backscatter with clinical parameters for all participants, only log-transformed plasma renin activity was correlated significantly with cyclic variation of integrated backscatter. One year after adrenalectomy, interventricular septal thickness, left ventricular posterior wall thickness, and left ventricular mass index decreased significantly. In addition, cyclic variation of integrated backscatter increased significantly after adrenalectomy (7.1 ± 2.1 to 8.5 ± 1.5 dB, P = .02). CONCLUSION Adrenalectomy not only reversed left ventricular geometry but also altered myocardial texture in patients with unilateral hyperaldosteronism. This finding implies that increases in collagen content in the myocardium of patients with unilateral hyperaldosteronism might be reversed by adrenalectomy.

Identification of a novel FN1–FGFR1 genetic fusion as a frequent event in phosphaturic mesenchymal tumour

Phosphaturic mesenchymal tumours (PMTs) are uncommon soft tissue and bone tumours that typically cause hypophosphataemia and tumour‐induced osteomalacia (TIO) through secretion of phosphatonins including fibroblast growth factor 23 (FGF23). PMT has recently been accepted by the World Health Organization as a formal tumour entity. The genetic basis and oncogenic pathways underlying its tumourigenesis remain obscure. In this study, we identified a novel FN1–FGFR1 fusion gene in three out of four PMTs by next‐generation RNA sequencing. The fusion transcripts and proteins were subsequently confirmed with RT‐PCR and western blotting. Fluorescence in situ hybridization analysis showed six cases with FN1–FGFR1 fusion out of an additional 11 PMTs. Overall, nine out of 15 PMTs (60%) harboured this fusion. The FN1 gene possibly provides its constitutively active promoter and the encoded proteins oligomerization domains to overexpress and facilitate the activation of the FGFR1 kinase domain. Interestingly, unlike the prototypical leukaemia‐inducing FGFR1 fusion genes, which are ligand‐independent, the FN1–FGFR1 chimeric protein was predicted to preserve its ligand‐binding domains, suggesting an advantage of the presence of its ligands (such as FGF23 secreted at high levels by the tumour) in the activation of the chimeric receptor tyrosine kinase, thus effecting an autocrine or a paracrine mechanism of tumourigenesis. Copyright

Diabetes and thyroid cancer risk: literature review.

Diabetic patients have a higher risk of various types of cancer. However, whether diabetes may increase the risk of thyroid cancer has not been extensively studied. This paper reviews and summarizes the current literature studying the relationship between diabetes mellitus and thyroid cancer, and the possible mechanisms linking such an association. Epidemiologic studies showed significant or nonsignificant increases in thyroid cancer risk in diabetic women and nonsignificant increase or no change in thyroid cancer risk in diabetic men. A recent pooled analysis, including 5 prospective studies from the USA, showed that the summary hazard ratio (95% confidence interval) for women was 1.19 (0.84–1.69) and was 0.96 (0.65–1.42) for men. Therefore, the results are controversial and the association between diabetes and thyroid cancer is probably weak. Further studies are necessary to confirm their relationship. Proposed mechanisms for such a possible link between diabetes and thyroid cancer include elevated levels of thyroid-stimulating hormone, insulin, glucose and triglycerides, insulin resistance, obesity, vitamin D deficiency, and antidiabetic medications such as insulin or sulfonylureas.

A Review on the Association between Glucagon-Like Peptide-1 Receptor Agonists and Thyroid Cancer

There is a concern on the risk of thyroid cancer associated with glucagon-like peptide-1 (GLP-1) analogs including liraglutide and exenatide. In this article, we review related experimental studies, clinical trials and observational human studies currently available. In rodents, liraglutide activated the GLP-1 receptors on C-cells, causing an increased incidence of C-cell neoplasia. Animal experiments with monkeys demonstrated no increase in calcitonin release and no C-cell proliferation after long-term liraglutide administration. Longitudinal 2-year data from clinical trials do not support any significant risk for the activation or growth of C-cell cancer in humans in response to liraglutide. However, an analysis of the FDA adverse event reporting system database suggested an increased risk for thyroid cancer associated with exenatide after its marketing. Noticeably, a recent study discovered that GLP-1 receptor could also be expressed in human papillary thyroid carcinomas (PTC), but the impact of GLP-1 analogs on PTC is not known. Therefore, GLP-1 analogs might increase the risk of thyroid C-cell pathology in rodents, but its risk in humans awaits confirmation. Since GLP-1 receptor is also expressed in PTC besides C-cells, it is important to investigate the actions of GLP-1 on different subtypes of thyroid cancer in the future.

Measurement of Waist Circumference Midabdominal or iliac crest

OBJECTIVE Waist circumference (WC) is used to define central obesity. This study aimed to compare the performance of two recommended locations of WC measurement. RESEARCH DESIGN AND METHODS A cohort of 1,898 subjects who were without diabetes from 2006 to 2012 were followed for a median of 31 months (Taiwan Lifestyle Study). The WC-IC, recommended by the National Cholesterol Education Program Third Adult Treatment Panel, was measured at the superior border of the iliac crest, and the WC-mid, recommended by World Health Organization and International Diabetes Federation, was measured midway between the lowest ribs and the iliac crest. The abdominal subcutaneous fat area (SFA) and visceral fat area (VFA) were assessed by computed tomography. RESULTS There was greater difference between WC-IC and WC-mid measurements in women than in men (P < 0.001). Both WC-IC and WC-mid correlated significantly with BMI, VFA, and SFA (all P < 0.001). WC-mid was better correlated to VFA than WC-IC, particularly in women, and it correlated more strongly to blood pressure, plasma glucose, hemoglobin A1c, triglyceride levels, HDL cholesterol, and C-reactive protein (all P < 0.05). The association of WC-mid with hypertension, diabetes, and metabolic syndrome was slightly better than that of WC-IC (area under the receiver operator curve 0.7 vs. 0.69, 0.71 vs. 0.68, and 0.75 vs. 0.7, respectively; all age-adjusted P < 0.05). With 90 cm (male)/80 cm (female) as criteria for central obesity, WC-mid, but not WC-IC, predicted the incidence of diabetes development (age-adjusted P = 0.003). CONCLUSIONS WC-mid is a better measurement to define central obesity than WC-IC, particularly in women.

Follicular variant of papillary thyroid carcinoma : Diagnostic limitations of fine needle aspiration cytology

OBJECTIVE To study the diagnostic sensitivity and specificity of fine needle aspiration cytology (FNAC) offollicular variant of papillary thyroid carcinoma (FVPTC). STUDY DESIGN The study group consisted of 390 papillary thyroid carcinoma (PTC) cases diagnosed histologically with thyroidectomy specimens. The FNAC and histopathologic classification were compared in terms of the appearance of FVPTC and non-FVPTC statistically with the chi squared test. Also, several features of the cytologic smears of FVPTC were reviewed. RESULTS Twelve of the 390 PTC cases were classified as FVPTC histologically. Five of the 12 cases were also reported as FVPTC in the diagnosis by FNAC and the other 7 as the usual type of PTC (UTPTC). There was 1 case classified as UVPTC histologically but FVPTC cytologically. If we use histologic diagnosis as the gold standard, the sensitivity and specificity of FNAC diagnosis of FVPTC were 42% and 83%, respectively. CONCLUSION FNAC may be a good tool for diagnosing PTC, but it is unreliable to differentiate between FVPTC and UTPTC.