Biomedical subjects

Tae Yong Kim

Publications and source records attributed to Tae Yong Kim.

At least 19 recordsLinked to original sources

PubMed2006

Systems biology as a foundation for genome-scale synthetic biology.

As the ambitions of synthetic biology approach genome-scale engineering, comprehensive characterization of cellular systems is required, as well as a means to accurately model cell-scale molecular interactions. These requirements are coincident with the goals of systems biology and, thus, systems biology will become the foundation for genome-scale synthetic biology. Systems biology will form this foundation through its efforts to reconstruct and integrate cellular systems, develop the mathematics, theory and software tools for the accurate modeling of these integrated systems, and through evolutionary mechanisms. As genome-scale synthetic biology is so enabled, it will prove to be a positive feedback driver of systems biology by exposing and forcing researchers to confront those aspects of systems biology which are inadequately understood.

Biology↗

PubMed2006

Lymphovascular invasion is associated with lateral cervical lymph node metastasis in papillary thyroid carcinoma.

OBJECTIVES: The objective of this retrospective study to evaluate whether lymphovascular invasion (LVI) is associated with lateral cervical lymph node metastasis and tumor recurrence in papillary thyroid carcinoma (PTC). METHODS: We evaluated the medical records of patients with PTC who had undergone total thyroidectomy and subsequent I remnant ablation at Asan Medical Center, Seoul, Korea, from January 1997 thorough December 2000. RESULTS: A total of 662 patients (585 women and 77 men; mean age, 44.8 years) with PTC were enrolled in the study. Of these patients, 33 were found to have LVI. We found a significant association between LVI and lateral cervical lymph node metastasis at the time of initial surgery (P = .001). Multivariate analyses adjusting for clinicopathologic parameters known to predict recurrence such as age, gender, tumor size, extrathyroid extension, and multifocality also showed a significant association between LVI and lateral cervical lymph node metastasis. For the 633 patients without distant metastasis at the time of initial surgery, LVI was also significantly associated with tumor recurrence during the follow-up period (median, 68 months; range, 3-108 months): 29% versus 13.6% for patients with and without LVI, respectively (P = .048 by log-rank test). However, this association was lost on multivariate analyses adjusting for conventional clinicopathologic predictors of recurrence. CONCLUSIONS: In patients with PTC, LVI is associated with lateral cervical lymph node metastasis and clinical recurrence.

Adult↗

PubMed2006

The BRAF mutation is useful for prediction of clinical recurrence in low-risk patients with conventional papillary thyroid carcinoma.

BACKGROUND: The activating BRAF(V600E) mutation is the most common genetic alteration reported in papillary thyroid carcinoma (PTC). While some reports suggest the BRAF(V600E) mutation is associated with factors predicting a poor prognosis and recurrence, this remains a controversial issue. AIM: To determine whether the presence of the BRAF(V600E) mutation is a prognostic indicator for clinical recurrence in low-risk patients with conventional PTC. PATIENTS AND METHODS: The study involved 203 conventional PTC patients who underwent total or near-total thyroidectomy followed by immediate 131I ablation of the remnants. Patients with antithyroglobulin antibodies and those with extracervical metastases at presentation were excluded. DNA was extracted from paraffin-embedded tumour specimens, and the presence of the BRAF(V600E) mutation was evaluated using PCR amplification and direct sequencing. RESULTS: The BRAF(V600E) mutation was found to be present in 149 (73.4%) of 203 patients. The BRAF(V600E) mutation was correlated with male gender (P = 0.006) and with tumour size (P = 0.005). While there appeared to be an association between the BRAF(V600E) mutation and extrathyroid extension, this did not reach statistical significance (P = 0.062). During follow-up of the 203 patients (median 7.3 years; range 0.7-10.0 years), 36 (18%) patients experienced recurrence. While univariate analysis showed the BRAF(V600E) mutation was associated with tumour recurrence (21% with mutation vs 7% without mutation; P = 0.037), this association was not shown following multivariate analyses adjusting for the clinicopathological prognostic factors of age, gender, tumour size, extrathyroid extension, multifocality and lymph node metastasis. CONCLUSIONS: Although the BRAF(V600E) mutation was found to be associated with a higher clinical recurrence of disease in low-risk conventional PTC patients, it was not an independent predictor.

Adult↗

PubMed2005

In vivo antitumor efficacy and cardiotoxicity of novel anthracycline ID6105 (11-hydroxy-aclacinomycin X, Hyrubicin).

Hybrid biosynthetic approach produced a new anthracycline ID6105 (11-hydroxyaclacinomycin X, Hyrubicin), which has potent antitumor activities against a broad range of cancer cell lines. Like other anthracyclines, ID6105 has the inhibitory effects on DNA synthesis as well as topoisomerase II. As preclinical studies of ID6105, we investigated ID6105's efficacy on human tumors, and cardiotoxicity. In human tumor xenografts, the ID6105's antitumor effects were greater than other anticancer drugs. ID6105 induced tumor regression in Hep G2 human hepatoma model, and slowed down the tumor growth rates in several tumor models. Doxorubicin-refractory tumors such as PC-3, DU-145, and CX-1 were sensitive to ID6105, and the growth of EKVX, lung cancer, which did not respond to paclitaxel, was also inhibited by ID6105, but tumor mass in CFPA, MCF7, and HCT-15 was not reduced by ID6105. The cardiotoxicity of ID6105 has also been assessed in rats. ID6105 did not induce any remarkable histopathological changes in hearts, and its lipid peroxidation in rat cardiac muscles did not occur as much as doxorubicin, indicating that the cardiotoxicity of ID6105 is remarkably lower than that of doxorubicin. Taking all into account, our results suggest that ID6105 would be a promising candidate for a novel anthracycline chemotherapeutic agent.

Aclarubicin↗

PubMed2005

Pharmacokinetics of 11-hydroxyaclacinomycin X (ID-6105), a novel anthracycline, after i.v. bolus multiple administration in rats.

We investigated the pharmacokinetics of 11-hydroxyaclacinomycin X (ID-6105), a novel anthracycline, after intravenous (i.v.) bolus administration at a multiple dose every 24 h for 5 days in rats. To analyze ID-6105 levels in biological samples, we used an HPLC-based method which was validated in a pharmacokinetic study by suitable criteria. The concentrations of ID-6105 after the multiple administration for 5 days were not significantly different from the results after the single administration. The t1/2alpha, t1/2beta, Vdss, and CLt after the multiple administration were not significantly different from the values after the single administration. Moreover, the concentrations of ID-6105 1 min at day 1-5 after i.v. bolus multiple administration did not show the significant difference. Of the various tissues, ID-6105 mainly distributed to the kidney, lung, spleen, adrenal gland, and liver after i.v. bolus multiple administration. ID-6105 concentrations in the kidney or lung 2 h after i.v. bolus administration were comparable to the plasma concentration shortly after i.v. bolus administration. However, the ID-6105 concentrations in various tissues 48 h after i.v. bolus administration decreased to low levels. ID-6105 was excreted largely in the bile after i.v. bolus multiple administration at the dose of 3 mg/kg. The amounts of ID-6105 found in the bile by 12 h or in the urine by 48 h after the administration were calculated to be 14.1% or 4.55% of the initial dose, respectively, indicating that ID-6105 is mostly excreted in the bile. In conclusion, ID-6105 was rapidly cleared from the blood and transferred to tissues, suggesting that ID-6105 might not be accumulated in the blood following i.v. bolus multiple dosages of 3 mg/kg every 24 h for 5 days. By 48 h after i.v. bolus administration, ID-6105 concentrations in various tissues had decreased to very low levels. The majority of ID-6105 appears to be excreted in the bile.

Aclarubicin↗

PubMed2005

Association of HLA-DR and -DQ genes with Graves disease in Koreans.

Graves disease (GD) is an autoimmune thyroid disease and is associated with human leukocyte antigen (HLA)-DR3 and DQA1*0501 in Caucasians. However, the association of HLA with GD is less clear-cut in East Asian populations. We analyzed HLA-DRB1 and -DQB1 associations with GD in 198 Korean patients compared with 200 healthy controls. HLA-DRB1*0803 (27.8% vs. 14.5% in controls, OR = 2.27, corrected p [p(c)] = 0.03) and *1602 (5.1% vs. 0%, OR = 22.34, p(c) = 0.03) alleles and closely linked haplotypes, DRB1*0803-DQB1*0601 and DRB1*1602-DQB1*0502, conferred susceptibility to GD in Koreans. Weak association of DRB1*0301 with GD susceptibility was observed in male patients only (12.5% vs. 3.5%, OR = 3.57, p < 0.05). HLA-DRB1*0101, *0701, *1202, and *1302 alleles were weakly associated with resistance to the disease (OR < 0.5, p < 0.05). Some HLA alleles were weakly associated with clinical characteristics in GD patients. Patients with DRB1*1301-DQB1*0603 developed their diseases in younger ages and were more frequently associated with larger goiter (p < 0.05). Although HLA class II alleles associated with GD in Koreans were different from those in Caucasians, some associations are shared, such as association of DRB1*0301 in male patients and protective effect of DRB1*0701 to GD susceptibility.

Adolescent↗

PubMed2005

Systems biotechnology for strain improvement.

Various high-throughput experimental techniques are routinely used for generating large amounts of omics data. In parallel, in silico modelling and simulation approaches are being developed for quantitatively analyzing cellular metabolism at the systems level. Thus informative high-throughput analysis and predictive computational modelling or simulation can be combined to generate new knowledge through iterative modification of an in silico model and experimental design. On the basis of such global cellular information we can design cells that have improved metabolic properties for industrial applications. This article highlights the recent developments in these systems approaches, which we call systems biotechnology, and discusses future prospects.

Genome↗

PubMed2005

18F-fluorodeoxyglucose uptake in thyroid from positron emission tomogram (PET) for evaluation in cancer patients: high prevalence of malignancy in thyroid PET incidentaloma.

OBJECTIVES: To investigate the prevalence of incidental thyroid F-fluorodeoxyglucose (FDG) uptake in positron emission tomogram (PET) scan for evaluation in cancer patients and the role of standard uptake value (SUV) measurement in differentiation of thyroid malignancy from benign disease. STUDY DESIGN: Retrospective single-center study. METHODS: Four thousand one hundred thirty-six subjects had been given FDG-PET scan for evaluation of known malignancies not associated with thyroid. The maximum SUVs of the thyroid lesions were recorded and reviewed. Fine needle aspiration was performed in patients with definite nodule by palpation or ultrasonography. RESULTS: Ninety-four (2.2%) were identified to have focal (n = 45, 1.1%) or diffuse (n = 45, 1.1%) thyroid FDG uptake. The incidence of focal or diffuse thyroid FDG uptake was higher in women (2.7% or 1.9%) than in men (0.4% or 0.7%). Cytologic diagnosis was available in 32 of 45 focal thyroid FDG uptakes. In 16 (50%) patients, the tumor was found to be malignant; 14 were papillary thyroid carcinoma (surgically confirmed in 7 cases), 2 were metastatic tumor from breast and esophagus. Sixteen were cytologically diagnosed as follicular cell lesions: follicular neoplasm (n = 2), nodular hyperplasia (n = 7), indeterminate follicular lesion (n = 7). There was no significant difference in maximum SUV between benign and malignant nodules. From 45 patients with diffuse thyroid FDG uptake, presumptive diagnosis of chronic thyroiditis was possible in 34 patients by clinical and laboratory findings. CONCLUSION: Our data suggest that a cytologic diagnosis of focal thyroid FDG-PET incidentaloma regardless of SUV is mandatory considering the very high prevalence of thyroid malignancy.

Adolescent↗

PubMed2005

Metastasis to the thyroid diagnosed by fine-needle aspiration biopsy.

BACKGROUND: Metastasis to the thyroid is uncommon, but the number of cases seems to have increased in recent years. This increase may be related to more frequent use of fine-needle aspiration biopsy (FNAB) in any suspected case. DESIGN: A retrospective review of patients with thyroid metastasis diagnosed by FNAB at the Asan Medical Centre. PATIENTS: Twenty-two patients who were seen at the Asan Medical Centre between 1997 and 2003. Median age was 55 years with range between 34 and 74 years. RESULTS: Fourteen patients presented with a palpable thyroid nodule. Eight patients had an impalpable thyroid nodule that was found incidentally during the various imaging studies. The breast (five patients) was the most common primary site followed by the kidney (three), colon (three) and lung (three). FNAB confirmed metastatic disease in 19 patients and raised suspicion in three patients. The suspicion of metastasis to the thyroid was confirmed by Tru-cut needle core biopsy in one patient and surgery in two patients. Thyroid metastases were found during the initial work-up for primary tumour in eight patients. In the remaining 14 patients, the interval from diagnosis of primary tumour to the detection of thyroid metastasis varied from 8 months to 15 years, with a median of 54 months. Fifteen patients had metastatic disease elsewhere at the time of presentation. Ten patients received chemotherapy. Radiotherapy was used in two patients. Seven patients are still alive, with one patient disease free for 16 months following resection of the thyroid metastasis. CONCLUSIONS: Thyroid metastases are uncommon but can be detected more frequently with routine use of FNAB. Breast cancer is the most common tumour that metastasizes to the thyroid. They usually occur when there are metastases elsewhere, sometimes many years after the diagnosis of the original primary tumour and show poor prognosis in general.

Adenocarcinoma↗

PubMed2005

Arg16Gly polymorphism in beta2-adrenergic receptor gene is not associated with thyrotoxic periodic paralysis in Korean male patients with Graves' disease.

BACKGROUND: Thyrotoxic periodic paralysis (TPP) occurs most frequently in Asian males and present with an acute episode of proximal muscle weakness in the setting of thyrotoxicosis. Despite the fact that mutations were described in genes encoding ion channels in familial hypokalaemic periodic paralysis, no definite genetic variants were found in TPP. beta2-adrenergic receptors (ADRB2s) are expressed in skeletal muscle and stimulate the sodium pump. Single nucleotide polymorphisms in ADRB2 gene were identified and may act as disease modifiers in various diseases. OBJECTIVE: We were to demonstrate that ADRB2 gene might be a susceptibility gene for TPP in Korean male patients with Graves' disease. DESIGN AND PATIENTS: In a series of 28 male TPP patients and 31 control patients, three polymorphisms in ADRB2 gene have been studied: a T to C substitution at -47 (-47T/C), Arg16Gly and Gln27Glu. Control patients were male Graves' patients without history of paralysis. RESULTS: The distributions of the -47C, Gly16 and Glu27 alleles in all patients were 0.02, 0.34 and 0.02, respectively. The genotype Arg16/Arg16 was not significantly associated with TPP (odds ratio 0.53; 95% confidence interval, 0.19-1.50; corrected P = 0.897). Also, the frequency of genotype Gly16/Gly16 was not significantly different in TPP patients than in controls (0.07 vs. 0.23; odds ratio, 0.26; 95% confidence interval, 0.05-1.40; corrected P = 0.45). Allele frequencies of ADRB2 in patients with TPP did not differ from controls. CONCLUSIONS: The polymorphism of the ADRB2 gene may not confer genetic susceptibility to TPP in Korean male patients with Graves' disease.

Adolescent↗

PubMed2005

The BRAF mutation is not associated with poor prognostic factors in Korean patients with conventional papillary thyroid microcarcinoma.

BACKGROUND: The BRAF(V600E) mutation, the most common genetic alteration reported in papillary thyroid carcinoma, has been associated with poor prognostic factors. AIM: To determine whether the presence of the BRAF(V600E) mutation is associated with poor prognosis in Korean patients with conventional papillary thyroid microcarcinoma (micro-PTC). PATIENTS AND METHODS: DNA was extracted from paraffin-embedded thyroid tumour specimens taken from 60 patients with conventional micro-PTC, as well as from nine patients with follicular variant papillary carcinoma, six with nodular hyperplasia, four with follicular carcinoma (including one with Hürthle cell carcinoma), four with follicular adenoma (including two with Hürthle cell adenoma) and one each with medullary carcinoma, poorly differentiated carcinoma and anaplastic carcinoma. The presence of the BRAF(V600E) mutation was determined by polymerase chain reaction (PCR) amplification of exon 15 followed by direct sequencing. RESULTS: The BRAF(V600E) mutation was detected in tumour samples from 31 of 60 conventional micro-PTC patients (52%), but was not detected in patients with other types of thyroid tumours. The age distribution, tumour size, extrathyroid extension, multifocality and staging did not differ significantly between patients with and without the BRAF(V600E) mutation. CONCLUSION: In Korean patients with conventional micro-PTC, the presence of the BRAF(V600E) mutation was not significantly associated with prognostic factors.

Adenoma↗

PubMed2005

Metabolic engineering of Escherichia coli for enhanced production of succinic acid, based on genome comparison and in silico gene knockout simulation.

Comparative analysis of the genomes of mixed-acid-fermenting Escherichia coli and succinic acid-overproducing Mannheimia succiniciproducens was carried out to identify candidate genes to be manipulated for overproducing succinic acid in E. coli. This resulted in the identification of five genes or operons, including ptsG, pykF, sdhA, mqo, and aceBA, which may drive metabolic fluxes away from succinic acid formation in the central metabolic pathway of E. coli. However, combinatorial disruption of these rationally selected genes did not allow enhanced succinic acid production in E. coli. Therefore, in silico metabolic analysis based on linear programming was carried out to evaluate the correlation between the maximum biomass and succinic acid production for various combinatorial knockout strains. This in silico analysis predicted that disrupting the genes for three pyruvate forming enzymes, ptsG, pykF, and pykA, allows enhanced succinic acid production. Indeed, this triple mutation increased the succinic acid production by more than sevenfold and the ratio of succinic acid to fermentation products by ninefold. It could be concluded that reducing the metabolic flux to pyruvate is crucial to achieve efficient succinic acid production in E. coli. These results suggest that the comparative genome analysis combined with in silico metabolic analysis can be an efficient way of developing strategies for strain improvement.

Base Sequence↗

PubMed2005

HPLC analysis and pharmacokinetic characteristics of 11-hydroxyaclacinomycin X (ID-6105), a novel anthracycline, in rats and beagle dogs.

We investigated the pharmacokinetic characteristics of 11-hydroxyaclacinomycin X (ID-6105), a novel anthracycline, after intravenous (i.v.) bolus administration in rats and beagle dogs. We developed an HPLC-based method to analyze ID-6105 levels in plasma, bile, urine, feces, and tissue homogenates and validated the method in a pharmacokinetic study. The plasma concentration of ID-6105 decreased to below the quantifiable limit (0.02 microg/ml) at 4 and 8 h after i.v. administration in rats at doses of 2 and 10 mg/kg, respectively (t(1/2,alpha) and t(1/2,beta) of 0.78 and 17.8 min at a dose of 2 mg/kg, 0.91 and 176 min at a dose of 10 mg/kg, respectively). The AUC increased with nonlinear pharmacokinetics following the dosage increase from 2 to 10 mg/kg in rats, while the pharmacokinetics were not significantly altered in beagle dogs following a dosage increase from 0.5 to 2.5 mg/kg. Of the various tissues tested, ID-6105 was mainly distributed in the lung, spleen, kidney, adrenal gland, and liver after i.v. bolus administration. ID-6105 levels in the lung or kidney 2 h after i.v. bolus administration were comparable to the initial plasma concentration. However, the ID-6105 concentrations in various tissues 48 h after i.v. bolus administration became too small to measure. The cumulative amounts of ID-6105 found in the bile 48 h after the administration of 2 and 10 mg/kg were calculated to be 26.7 and 18.5% of the initial dose, respectively. The corresponding values in the urine 72 h after i.v. administration were 4.33 and 3.07% of the initial dose, suggesting that ID-6105 is mostly excreted in the bile. In conclusion, our observations indicate that ID-6105 was rapidly cleared from the blood and transferred to tissues such as the lung, spleen, kidney, and liver 2 h after i.v. bolus administration. Moreover, the majority of ID-6105 appears to be excreted in the bile by 24 h after i.v. bolus administration.

Aclarubicin↗

PubMed2005

Systemic inflammatory syndrome and hepatic inflammatory cell infiltration caused by an interleukin-6 producing pheochromocytoma.

Pheochromocytoma is a tumor that produces a variety of biologically active substances in addition to catecholamines. We report here a patient with a pheochromocytoma, who presented with acute inflammatory symptoms and marked abnormalities in liver function and hematological tests. A 31-year-old man, who had experienced intermittent fever, chills and weight loss during the previous several months, was referred to our hospital for further evaluation. Laboratory examination revealed anemia, leukocytosis with elevated inflammatory markers, and abnormalities in coagulation and liver function tests. Histological examination revealed a marked plasmacytosis in the bone marrow and lymphocyte infiltration into the portal area of the liver. Along with increases in serum catecholamine and urine catecholamine metabolites, his serum interleukin (IL)-6 level was increased to 300 pg/ml, compared with a normal range of 3-12 pg/ml. Left adrenalectomy was performed. The adrenal tumor was densely immunostained with antibody to IL-6. After resection of his adrenal tumor, his serum IL-6 level returned to normal (11 pg/ml) and all symptoms subsided with normalization of laboratory findings.

Acute Disease↗

PubMed2004

Serum thyroglobulin levels at the time of 131I remnant ablation just after thyroidectomy are useful for early prediction of clinical recurrence in low-risk patients with differentiated thyroid carcinoma.

We investigated whether serum thyroglobulin (Tg) measured at the time of remnant ablation (ablation-Tg) could be a prognostic indicator complementary to serum Tg levels at the time of the first diagnostic whole-body scan (WBS) after thyroid hormone withdrawal (control-Tg; approximately 6-12 months after ablation-Tg) and whether ablation-Tg could predict the persistence or recurrence of disease in low-risk patients with differentiated thyroid carcinoma. Patients with differentiated thyroid carcinoma (n = 268) treated with total or near-total thyroidectomy followed by immediate (131)I remnant ablation were studied. Patients with anti-Tg autoantibodies and those showing evidence of extracervical metastases were excluded. Two patients showing remnant uptake on follow-up diagnostic WBS received a second ablation. We found significant correlation between ablation-Tg and control-Tg levels; 114 of 143 patients (80%) with ablation-Tg greater than 2 microg/liter showed detectable (>/=1 microg/liter) control-Tg, and 70 of 125 (56%) patients with ablation-Tg 2 microg/liter or less showed undetectable (<1 microg/liter) control-Tg [odds ratio 5.1, 95% confidence interval (CI) 3.0-8.9, P < 0.001]. When the 268 patients were followed up for a mean period of 5.7 +/- 1.4 yr (range 2.8-8.3 yr), 35 (13%) had recurrences; 73 (27%) were classified as "Tg positive, no evidence of disease"; and 160 (60%) showed complete remission. Of 143 patients with ablation-Tg greater than 2 microg/liter, recurrence was observed in 33 cases (23%); "Tg positive, no evidence of disease," was observed in 52 cases (36%); and complete remission was observed in 58 cases (41%). Of 125 patients with ablation-Tg 2 microg/liter or less, two patients (2%) showed recurrence during the follow-up; 21 patients (17%) were regarded as "Tg positive, no evidence of disease"; and 102 patients (81%) showed complete remission. The positive predictive value for recurrence in patients having ablation-Tg greater than 2 microg/liter was found to be 23.1% (33 of 143 patients, 95% CI 16.4-30.8%). The negative predictive value for recurrence in patients having ablation-Tg 2 microg/liter or less was found to be 98.4% (123 of 125 patients, 95% CI 94.4-99.8%). These data indicate that serum Tg levels measured at the time of immediate postoperative (131)I remnant ablation correlated well with serum Tg levels at the time of the initial diagnostic WBS and had a complementary role for predicting persistence or recurrence of disease in the earliest postoperative period.

Adolescent↗

PubMed2004

Ultrasonographic screening for detection of thyroid cancer in patients with Graves' disease.

OBJECTIVE: We prospectively screened consecutive patients with Graves' hyperthyroidism by ultrasonography (USG), regardless of presence of palpable nodules, and evaluated patients with nodule(s) by fine-needle aspiration (FNA) and by resulting surgery to define the prevalence of thyroid cancer in patients with Graves' disease. METHODS: Two hundred and forty-five consecutive Graves' disease patients without prior thyroid surgery or radio-iodine treatment were enrolled at Asan Medical Centre endocrinology clinic. All patients with nodule(s) of 5 mm or greater were reviewed for evaluation by FNA, and of these 90.0% (n = 62) underwent FNA. All patients with suspicious/malignant cytology or those with positive immunostaining with GAL-3 antibody underwent surgery. RESULTS: Among 245 patients, thyroid nodule(s) were detected in 35.1% (86/245) by USG. Nodule prevalence significantly increased according to age, which was the only significant variable predicting the presence of nodule(s) in logistic regression analysis. Among patients with thyroid nodule(s), 69 patients had nodule(s) of 5 mm or greater in size, and 62 cases of them (90.0%) underwent FNA. In eight patients, thyroid cancers were histologically confirmed (all papillary thyroid cancers), so the prevalence of thyroid cancer was at least 3.3% (8/245) in Graves' patients. Of eight patients with thyroid cancer, only one case was detected by palpation and the other seven patients were detected only by USG. In pathologic examination, mean size of tumour was 10.0 +/- 6.7 mm (5-25 mm), three cases had extrathyroidal extension (37.5%), four cases had cervical node metastasis (50.0%) and one case had multifocal tumour (12.5%). Thus, five of eight patients had locally advanced cancers (pT4 or pN1 lesion), but none had distant metastasis. Prevalence of thyroid cancers in Graves' disease tended to be higher in patients of 45 years or greater than younger patients (6.7%vs. 1.3%, P = 0.05), and that of the locally advanced cancers was significantly higher in older patients (5.6%vs. 0%, P < 0.05). Older age of the patient was the only significant factor predicting the presence of locally advanced thyroid cancers regardless of duration/severity of hyperthyroidism, goitre size, or of TBII activity. CONCLUSIONS: The prevalence of thyroid cancer in Graves' patients was at least 3.3% in this prospective analysis; most of them were micropapillary thyroid cancers. Stimulating TSHR antibodies seems not to induce nodule/cancer formation and not to change biologic behaviour of thyroid cancers in Graves' patients. Graves' patients of 45 years of age or above are more likely to harbour locally advanced thyroid cancers than younger patients, regardless of duration or severity of hyperthyroidism, goitre size, or of TBII activity.

Adult↗

PubMed2004

Completion thyroidectomy in patients with thyroid cancer who initially underwent unilateral operation.

BACKGROUND: In some instances, thyroid cancer may be diagnosed with histological examination after resection of putative or suspected benign nodule. In these cases, completion thyroidectomy followed by radioiodine ablation is usually recommended to prevent recurrence. If small intrathyroidal cancer is found, completion thyroidectomy may not be performed. Many patients have separate cancers in the contralateral lobe and in these cases completion thyroidectomy is essential even though primary tumour is small and limited within thyroid. OBJECTIVE: We analysed the frequency of malignant lesions in the contralateral lobe after completion thyroidectomy and assessed the predictive factors that may anticipate the presence of malignant lesion that may necessitate completion thyroidectomy. PATIENTS: Between 1995 and 2001, 243 patients were operated under the cytological diagnosis of follicular neoplasm. A total of 214 of them underwent lobectomy and isthmectomy and 81 turned out to have malignant disease in the resected lobe and they underwent completion thyroidectomy within a week to 6 months after the permanent section diagnosis of cancer. Their mean age was 40.7 +/- 12.1 years (range 14-71 years). RESULTS: After initial surgery, 53 patients had follicular carcinoma, 24 papillary carcinoma, one Hürthle cell carcinoma, one medullary, one insular and one anaplastic carcinoma. Mean tumour size was 4.1 +/- 2.6 cm (range 0.9-11 cm). After completion thyroidectomy, factors predicting the presence of cancer in the contralateral lobe were assessed according to clinical parameters and pathologic findings in ipsilateral lobe. First surgery revealed cancer multifocality in 34 cases, perithyroidal tumour extension in six and regional lymph node metastases in three. After completion thyroidectomy, 29 of the 81 patients revealed additional cancer in the contralateral lobe. Age, sex, size or pathologic type of the primary tumour was not associated with the presence of additional tumour in the contralateral lobe. Cancer multifocality in the ipsilateral lobe was the only significant variable to predict the presence of additional cancer in the contralateral lobe (relative risk = 6.03, confidence interval 2.23-16.35). Coexistence of benign nodule in ipsilateral lobe was not associated with increased cancer risk in the contralateral lobe. CONCLUSIONS: When diagnosed as thyroid cancer after unilateral surgery, the only predictive factor for the presence of additional contralateral cancer was multifocality of cancer in the ipsilateral lobe. We suggest that completion thyroidectomy is mandatory if multifocal cancers are found in the resected lobe, even though the cancers are very small and limited within the thyroid.

Adolescent↗

PubMed2003

A C/T polymorphism in the 5'-untranslated region of the CD40 gene is associated with Graves' disease in Koreans.

The genetic loci conferring susceptibility to Graves' disease remain unclear. The aim of the present study was to examine a C/T polymorphism in the 5'-untranslated region of the CD40 gene and its relationship with autoimmune thyroid diseases in Koreans. The C/T polymorphism in the 5'-untranslated region of CD40 gene, clinical characteristics, and thyroid antibodies were analyzed in a series of Korean patients (132 with Graves' disease, 118 with Hashimoto's thyroiditis, and 164 normal controls). The CC genotype was significantly associated with Graves' disease (odds ratio, 1.93; 95% confidence interval, 1.21-3.09; corrected p = 0.019). On the other hand, the frequency of the TT genotype was significantly lower in Graves' patients than in controls (8% vs. 18%; odds ratio, 0.38; 95% confidence interval, 0.18-0.82; corrected p = 0.044). Allele frequencies in CD40 did not differ from controls in patients with Hashimoto's thyroiditis. In patients with Graves' disease, there were significant differences between genotypic groups in the activity of stimulating thyrotropin (TSH) receptor antibody. However, clinical characteristics and other thyroid antibodies were not significantly different. In conclusion, the C allele in the 5'-untranslated region of the CD40 gene may confer genetic susceptibility to Graves' disease in Koreans.

5' Untranslated Regions↗