Tien-Chun Chang

A prospective, multicentre study to investigate the efficacy, safety and tolerability of octreotide LAR® (long-acting repeatable octreotide) in the primary therapy of patients with acromegaly

Objective  To evaluate the efficacy, safety and tolerability of octreotide LAR® (long‐acting repeatable octreotide) in the primary therapy of acromegaly.

Cancer risks in a population with prolonged low dose-rate γ-radiation exposure in radiocontaminated buildings, 1983 – 2002

Purpose: To assess cancer risks in a population that received prolonged low dose-rate γ-irradiation for about 10 years as a result of occupying buildings containing 60Co-contaminated steel in Taiwan. Materials and methods: The cancer risks were compared with those populations with the same temporal and geographic characteristics in Taiwan by standardized incidence ratios (SIR), adjusted for age and gender. The association of cancer risks with excess cumulative exposure was further evaluated for their relative risks by the Poisson multiple regression analysis. Result: A total of 7271 people were registered as the exposed population, with 101,560 person-years at risk. The average excess cumulative exposure was approximately 47.8 mSv (range < 1 – 2,363 mSv). A total of 141 exposed subjects with various cancers were observed, while 95 developed leukemia or solid cancers after more than 2 or 10 years initial residence in contaminated buildings respectively. The SIR were significantly higher for all leukemia except chronic lymphocytic leukemia (n = 6, SIR = 3.6, 95% confidence interval [CI] 1.2 – 7.4) in men, and marginally significant for thyroid cancers (n = 6, SIR = 2.6, 95% CI 1.0 – 5.7) in women. On the other hand, all cancers combined, all solid cancers combined were shown to exhibit significant exposure-dependent increased risks in individuals with the initial exposure before the age of 30, but not beyond this age. Conclusions: The results suggest that prolonged low dose-rate radiation exposure appeared to increase risks of developing certain cancers in specific subgroups of this population in Taiwan.

Medullary thyroid carcinoma : Pitfalls in diagnosis by fine needle aspiration cytology and relationship of cytomorphology to ret proto-oncogene mutations

OBJECTIVE To elucidate the pitfalls in the diagnosis of medullary thyroid carcinoma (MTC) by fine needle aspiration cytology (FNAC) and the relationship of cytomorphology to RET proto-oncogene mutations. STUDY DESIGN Cytomorphology was reviewed in the fine needle aspiration slides of 34 patients with MTC proven by surgery and pathology. Germline or somatic RET proto-oncogene mutations were determined using polymerase chain reaction-based sequencing in 15 of 34 patients, and the relationship to cytomorphology was evaluated. RESULTS Twenty-eight (82.4%) of 34 cases were diagnosed correctly as MTC by FNAC, 3 cases were misdiagnosed as follicular neoplasm and 1 as desmoid, and 2 cases were suspicious for MTC. The main reason for misdiagnosis was overlooking the slight angular shape of the nuclei or atypical changes. In 15 of 34 cases with germline or somatic RET proto-oncogene mutations determined, 10 cases had a germline mutation, and 1 had only a somatic mutation. There were 4 cases that had neither germline nor somatic RET proto-oncogene mutations. Cells with small/round and spindled forms were the predominant findings of codon 918 ATG-->ACG mutation, and cells with small/round and large oval to polygonal forms were the main findings of codon 634 mutations. There were no misdiagnoses in patients with RET proto-oncogene mutations. CONCLUSION FNAC is a good diagnostic method for MTC. Codon 918 mutation correlates mainly with small/round and spindled cells and codon 634 with small/round, large oval to polygonal forms.

Estimates of Relative Risks for Cancers in a Population after Prolonged Low-Dose-Rate Radiation Exposure: A Follow-up Assessment from 1983 to 2005

Abstract Hwang, S-L., Hwang, J-S., Yang, Y-T., Hsieh, W. A., Chang, T-C., Guo, H-R., Tsai, M-H., Tang, J-L. Lin, I-F. and Chang, W. P. Estimates of Relative Risks for Cancers in a Population after Prolonged Low-Dose-Rate Radiation Exposure: A Follow-up Assessment from 1983 to 2005. Radiat. Res. 170, 143–148 (2008). Radiation effects on cancer risks in a cohort of Taiwanese residents who received protracted low-dose-rate γ-radiation exposures from 60Co-contaminated reinforcing steel used to build their apartments were studied, and risks were compared to those in other radiation-exposed cohorts. Analyses were based on a more extended follow-up of the cohort population in which 117 cancer cases diagnosed between 1983 and 2005 among 6,242 people with an average excess cumulative exposure estimate of about 48 mGy. Cases were identified from Taiwans National Cancer Registry. Radiation effects on cancer risk were estimated using proportional hazards models and were summarized in terms of the hazard ratio associated with a 100-mGy increase in dose (HR100mGy). A significant radiation risk was observed for leukemia excluding chronic lymphocytic leukemia (HR100mGy 1.19, 90% CI 1.01–1.31). Breast cancer exhibited a marginally significant dose response (HR100mGy 1.12, 90% CI 0.99–1.21). The results further strengthen the association between protracted low-dose radiation and cancer risks, especially for breast cancers and leukemia, in this unique cohort population.

Ultrasound-guided fine needle aspiration cytology of parathyroid lesions. A review of 72 cases.

OBJECTIVE To elucidate the specific cytomorphologic patterns and diagnostic pitfalls in fine needle aspiration cytology (FNAC) of parathyroid lesions. STUDY DESIGN Seventy-two cases of surgically excised and pathologically verified hyperparathyroidism (20 cases of parathyroid hyperplasia, 51 of parathyroid adenoma and one of parathyroid carcinoma) received preoperative, ultrasound-guided FNAC examination for enlarged parathyroid glands. The smears were reviewed and analyzed. RESULTS Parathyroid lesions were diagnosed cytologically in 60 cases (83.3%). The presence of colloidlike substance, macrophages or follicular structures in smears led to six cases (8.3%) being misinterpreted as thyroid lesions. The cellularity of the smears was insufficient for interpretation in six cases (8.3%); however, two of these cases were diagnosed by determination of parathyroid hormone (PTH) levels in the fluid. Parathyroid hyperplasia had more tightly cohesive cell clusters with monomorphism, while parathyroid adenoma had more dispersed or loosely cohesive cells with pleomorphism and anisokaryosis. High PTH concentration in an aspirate was noted in all four cases of cystic lesions.

Enigmatic Ectopic Fat: Prevalence of Nonalcoholic Fatty Pancreas Disease and Its Associated Factors in a Chinese Population

Background Fatty infiltration of the pancreas is an enigmatic manifestation of ectopic fat deposition in obesity. Studies have shown that pancreatic lipid accumulation interferes with insulin secretion in humans. However, the prevalence of fatty pancreas and its associated factors in the general population remain unclear. The aim of this study was to investigate the prevalence of fatty pancreas and its association with diabetes, nonalcoholic fatty liver disease (NAFLD), and cardiometabolic risk factors in a Chinese population. Methods and Results This was a cross‐sectional study. A total of 8097 subjects with or without fatty pancreas (n=1297 and 6800, respectively) were recruited. Each subject was assessed by using abdominal sonography to diagnose NAFLD and fatty pancreas. Clinical and metabolic parameters were compared between groups, and their associations with fatty pancreas were examined. The prevalence of fatty pancreas was 16%. The fatty pancreas group had a significantly greater proportion of subjects with diabetes (12.6% versus 5.2%) and NAFLD (67.2% versus 35.1%) than did the non–fatty pancreas group (P<0.001). In the logistic regression analysis, age (P<0.001), general or central obesity (P<0.001), diabetes (P<0.001), and NAFLD (P<0.001) were independently associated with fatty pancreas after adjustment for sex, lipid profile, alanine transaminase/aspartate transaminase ratio, hypertension, smoking, alcohol drinking, and exercise. Conclusions The prevalence of fatty pancreas is high in the general population. Both diabetes and NAFLD are important associated factors of fatty pancreas, independent of age, sex, adiposity, and other cardiometabolic risk factors.

Results and Predictability of Fat-Removal Orbital Decompression for Disfiguring Graves Exophthalmos in an Asian Patient Population

PURPOSE To evaluate proptosis reduction by fat-removal orbital decompression (FROD), to determine the incidence of postoperative diplopia, and to assess predictability of proptosis reduction per volume of resected orbital fat. DESIGN Cross-sectional study. METHODS One hundred and twenty patients (31 men; 89 women) with Graves ophthalmopathy were treated with FROD via the transforniceal approach on 222 orbits between April 2003 and April 2006. Fifteen (12.5%) patients exhibited preoperative diplopia; 105 (87.5%) were without diplopia; mean follow-up +/- standard deviation (SD) was 10.9 +/- 5.1 months (range, six to 37 months). Univariate and multivariate analyses were used to evaluate Hertel change with FROD by linear regression. The setting was thyroid eye disease special clinics at National Taiwan University Hospital. RESULTS Mean Hertel values +/- SD decreased from 20.3 +/- 1.8 mm (range, 16.5 to 26.0 mm) to 16.8 +/- 1.4 mm (range, 13.5 to 21.0). Mean proptosis reduction +/- SD was 3.6 +/- 1.0 mm (range, 1.5 to 7.5 mm). Mean volume of resected orbital fat +/- SD was 3.6 +/- 1.0 ml (range, 1.2 to 6.5 ml). New-onset diplopia was noted for 2.8% of patients after FROD. The final predictive equation for Hertel change is shown as: 0.72 x removal of intraconal fat (ml) - 0.001 x age (yrs) - 0.22 x gender (male, 1; female, 0) - 0.19 x preoperative diplopia (yes, 1; no, 0) + 1.02. CONCLUSIONS FROD can achieve reasonable proptosis reduction and can reduce incidence of new-onset diplopia for patients with disfiguring Graves exophthalmos. The volume of resected orbital fat correlates with mean Hertel value change. The amount of resected orbital fat may predict proptosis reduction.

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.

Slow-release lanreotide in Graves' ophthalmopathy: A double-blind randomized, placebo-controlled clinical trial.

SS analogs are an attractive alternative in treating Graves’ ophthalmopathy (GO). Most of the previous studies were uncontrolled and enrolled few patients. The present study was conducted as a larger scale, prospective, randomized controlled study to determine the effectiveness of a slow-release formulation of lanreotide in GO. Sixty patients with active GO received an im injection every two weeks of either lanreotide 30 mg or placebo for 12 weeks. They were then followed and further treated in the traditional way if necessary. The Clinical Activity Score (CAS) was the primary efficacy criterion. Proptosis, diplopia, corneal erosion or ulcer, visual acuity, extraocular muscle movement and intraocular pressure were also evaluated. At the end of the 12 weeks, the mean CAS was not significantly decreased in the lanreotide group compared to the placebo group. The overall mean difference of proptosis between these two groups also did not reach significance at 12 weeks. Only diplopia at downward gaze had significant improvement for the lanreotide-treated group vs placebo group (p=0.03). No differences were observed between the two groups compared to other outcome measures. During the 24-month follow-up after the clinical trial, 14 patients received eye surgery in the placebo group compared with 10 patients in the lanreotide group (p=0.29). Six patients received methylprednisolone pulse therapy in the placebo group and two patients in the lanreotide group (p=0.25). In conclusion, lanreotide treatment had no significant effects on GO compared with placebo.

Demonstration of thyrotropin receptor mRNA in orbital fat and eye muscle tissues from patients with Graves’ ophthalmopathy by in situ hybridization

There is a controversy regarding whether there are thyrotropin (TSH) receptors in orbital fat and eye muscle tissues that may play a role in the pathogenesis of Graves’ ophthalmopathy. To elucidate whether there are TSH receptors in orbital fat and eye muscle tissues in patients with Graves’ ophthalmopathy, we applied the method of in situ hybridization in orbital fat and eye muscle tissues obtained during the operation for patients with Graves’ ophthalmopathy, to directly detect TSH receptor mRNA. To identify whether the cells with positive TSH receptor mRNA are fibroblasts, we also did vimentin immunoreactivity study. To further prove the transcript does have a full length of TSH receptor, the samples of total RNA preparations, extracted from orbital fat and eye muscle tissues, were used as a template for reverse transcriptase polymerase chain reaction (RT-PCR) using three primer sets to generate cDNA fragments and cloned for sequencing. The results showed that the expression of TSH receptor mRNA was demonstrated in adipocytes and fibroblasts of orbital fat, and perimysial fibroblasts within eye muscle tissues by in situ hybridization and vimentin immunoreactivity study. Also, by using the RT-PCR, cloning and sequencing, we further proved that the transcript does have a full length of TSH receptor. The present study suggested that there are TSH receptors expressed in orbital fat and eye muscle tissues.