Biomedical subjects

Kanji Kuma

Publications and source records attributed to Kanji Kuma.

At least 19 recordsLinked to original sources

PubMed2006

Effect of levo-thyroxine replacement on non-high-density lipoprotein cholesterol in hypothyroid patients.

CONTEXT: Recently, non-high-density lipoprotein cholesterol (non-HDL-C), a measure of total cholesterol minus HDL-C, has emerged as a predictor of cardiovascular disease. OBJECTIVE: We evaluated the effect of L-T4 replacement on non-HDL-C levels in patients with primary hypothyroidism. METHODS: Thirteen patients with overt hypothyroidism and 26 patients with subclinical hypothyroidism participated in the study. The lipid profiles, including non-HDL-C, were measured in patients with hypothyroidism before and 3 months after L-T4 replacement was started. RESULTS: After L-T4 replacement, the serum concentrations of all lipoproteins, exclusive of lipoprotein (a) [Lp(a)], were significantly decreased in patients with overt hypothyroidism. In patients with subclinical hypothyroidism, the serum concentrations of total cholesterol, non-HDL-C, remnant-like particle cholesterol, and apolipoprotein B (Apo B) were significantly decreased, whereas no significant changes in the serum concentrations of low-density lipoprotein cholesterol, HDL-C, triglycerides, apolipoprotein A-I, and Lp(a) were observed. In all 39 patients, the reduction in the non-HDL-C levels correlated with the reduction in the low-density lipoprotein cholesterol, remnant-like particle cholesterol, and Apo B levels. However, the reduction in the non-HDL-C levels did not correlate with the reduction in the HDL-C, Lp(a), and apolipoprotein A-I levels. CONCLUSIONS: This study is the first to show that L-T4 replacement may reduce serum concentrations of non-HDL-C in patients with hypothyroidism. The study also suggests that such altered serum concentrations of non-HDL-C in hypothyroidism may be related to the disturbed metabolism of low-density lipoprotein, remnant lipoprotein, and Apo B.

Adult↗

PubMed2006

Sporadic congenital hyperthyroidism due to a germline mutation in the thyrotropin receptor gene (Leu 512 Gln) in a Japanese patient.

Constitutively activating thyrotropin receptor (TSHR) germline mutations have been identified as a molecular cause of congenital hyperthyroidism. We here describe a Japanese woman who had presented with severe hyperthyroidism and advanced bone age as a neonate. She underwent neurosurgical intervention for craniosynostosis, and presented with perodactylia and mild mental retardation with hydrocephalus. Hyperthyroidism has been refractory to antithyroid drug therapy in the absence of antithyrotropin receptor antibodies during follow-up of 20 years, resulting in an enlarged goiter. Analysis of the patient's genomic DNA showed a heterozygous thymine-to-adenine point mutation in exon 10 of TSHR at position 1535 which was not present in the parents' DNA. This mutation, changing leucine to glutamine in codon 512 in the third transmembrane region, was previously identified as a somatic mutation in toxic thyroid nodules and was shown to increase basal cAMP production in vitro. To our knowledge, this is the first report of a germline mutation of TSHR causing sporadic congenital nonautoimmune hyperthyroidism in a Japanese patient.

Adult↗

PubMed2006

Two-day thionamide withdrawal prior to radioiodine uptake sufficiently increases uptake and does not exacerbate hyperthyroidism compared to 7-day withdrawal in Graves' disease.

The appropriate period of antithyroid drug (ATD) discontinuation before radioiodine therapy is the most critical problem in Graves' disease patients under going treatment with ATD. To determine the optimal period that does not alter the outcome of radioiodine therapy or exacerbate hyperthyroidism, we compared serum FT4 levels at radioiodine uptake (RAIU) and therapy outcomes between a 2-day withdrawal group and 7-day withdrawal group. We prospectively recruited 43 patients for the 2-day withdrawal protocol and retrospectively reviewed 49 patients treated with radioiodine following the protocol of 7-day withdrawal. There was no significant difference in RAIU between the 2 groups. The mean serum FT4 level measured on the first day of 24-h RAIU of the 7-day group was significantly higher than that in the 2-day group. There were no significant differences in the outcomes at each point (6 months, 1 year, and 2 years after therapy) between the 2 groups. Our results indicated that withdrawal of ATD for 2 days is superior to 7 days in that 2 days discontinuation did not exacerbate hyperthyroidism. In order to prevent serum thyroid hormone increase after ATD withdrawal and radioiodine therapy, a 2-day ATD withdrawal period before radioiodine therapy may be useful for high-risk patients such as the elderly and patients with cardiac complications. We believe that the 2-day ATD withdrawal method may be useful for patients undergoing treatment with ATD who are to undergo radioiodine therapy.

Adult↗

PubMed2006

Haplotype analysis reveals founder effects of thyroglobulin gene mutations C1058R and C1977S in Japan.

CONTEXT: Thyroglobulin (Tg) mutations were previously believed to be rare, resulting in congenital goitrous hypothyroidism. However, an increasing number of patients with Tg mutations, who are euthyroid to mildly hypothyroid, have been identified in Japan. OBJECTIVES: The purpose of this study was to investigate whether the three frequently found Tg mutations, namely C1058R, C1245R, and C1977S, were caused by a founder effect. RESULTS: We found 26 different mutations within the Tg gene in 52 patients from 41 families. Thirty-five patients were homozygous for the mutations, whereas the others were compound heterozygous. The occurrence of Tg mutation within the general Japanese population is one in 67,000. Patients with the C1245R mutation were found throughout Japan, whereas those with the C1058R mutation were confined to a small village on a southern island, and those with the C1977S mutation were restricted to a city. The eight patients with the C1058R mutation and the seven patients with the C1977S mutation all showed the same combinations of 18 single-nucleotide polymorphisms in the coding region of the Tg gene, which would appear in one in 810 million and one in 37 billion, respectively, control subjects. CONCLUSIONS: The frequently found mutations, C1058R and C1977S, were caused by founder effects. This result suggests that Tg mutations may provide a genetic basis for the cause of familial euthyroid goiter.

Founder Effect↗

PubMed2006

A case of hypothyroid Graves' disease following external radiation therapy to the cervical region.

A case of hypothyroid Graves' disease occurred following external radiation therapy to the cervical region is described. Severe hypothyroidism developed in a 56-year-old man 6 months after external radiation therapy for submandibular cancer. Serological evaluation of thyroid autoimmunity revealed the presence of antithyroid antibodies and thyrotropin-binding inhibitory immunogloblins (TBII). Diplopia, limitation of downward gaze, and palpebral edema developed 2 years after levothyroxine replacement therapy. Ocular magnetic resonance imaging revealed marked hypertrophy of the bilateral extraocular muscles with signal hyperintensity on T2-weighted images. This infiltrative ophthalmopathy showed marked improvement after additional treatment with high-dose methylprednisolone and orbital radiation, in parallel with a decrease in TBII. These results suggest that radiation-associated thyroidal injury might be associated with the etiology of hypothyroid Graves' disease.

Carcinoma, Squamous Cell↗

PubMed2006

Four cases of Graves' disease which developed after painful Hashimoto's thyroiditis.

We report four cases of Graves' disease that developed after painful Hashimoto's thyroiditis. All were middle-aged women, who had high titers of anti-thyroid antibodies and thyrotoxicosis at the onset of painful Hashimoto's thyroiditis. After 2 to 7 years, they developed Graves' disease with positive antibody against the thyrotropin receptor. Their clinical courses of Graves' disease went favorably due to the treatment with antithyroid drug or radioactive iodine therapy. Painful Hashimoto's thyroiditis is an atypical variant of Hashimoto's thyroiditis and is one form of destructive thyroiditis. Thyroid damage due to painful Hashimoto's thyroiditis may be associated with the development of Graves' disease.

Antithyroid Agents↗

PubMed2006

Clinical significance of metastasis to the central compartment from papillary microcarcinoma of the thyroid.

We previously demonstrated that for papillary microcarcinoma (PMC), (1) patients with lateral lymph node metastasis detected on preoperative ultrasonography (US) are more likely to develop recurrence, and (2) dissection of the lateral compartment does not improve the prognosis of patients without US-detectable lateral metastasis. In this study, we focused on metastasis from PMC to the central compartment. We investigated the clinical significance of lymph nodes in the central compartment using the same series of 600 patients as used in the previous study. Ultrasound-diagnosed central node metastasis could be found in 30 patients (20.0%). Although the specificity of US for detecting central node metastasis was 99.1%, sensitivity was only 10.9%. Neither US-diagnosed nor pathologically confirmed central node metastasis affected the disease-free survival (DFS) rate of PMC patients. Furthermore, in cases where PMC was located only in one lobe, central node dissection in the contralateral lobe did not improve the DFS rate. These findings suggest that, for PMC, (1) US is an insensitive technique for detecting the central node metastasis, (2) the presence of central node metastasis is unrelated to DFS of patients, and (3) when performing lobectomy for PMC involving only one lobe, dissection of the central compartment in the contralateral lobe is optional.

Adult↗

PubMed2006

Prognostic significance of extrathyroid extension of papillary thyroid carcinoma: massive but not minimal extension affects the relapse-free survival.

OBJECTIVES: Extrathyroid extension has been recognized as a prognostic factor in papillary thyroid carcinoma. In the most recent version of the UICC TNM classification system, extrathyroid extension has been classified into two grades, minimal extension (extension to sternothyroid muscle or perithyroid soft tissues) and massive extension (extension to subcutaneous soft tissue, larynx, trachea, esophagus, or recurrent laryngeal nerve). In this study, we investigated the prognostic significance of each of the two types of extension. PATIENTS AND METHODS: One thousand and sixty-seven patients with papillary thyroid carcinoma without distant metastasis at surgery, who underwent surgical treatment in Kuma hospital between 1990 and 1995 and had been followed postoperatively for 60 months or more, were enrolled in this study. The grading of extrathyroid extension was based on both pathological findings and intraoperative surgical findings. RESULTS: In univariate analysis, although patients with massive extension showed a significantly worse relapse-free survival (RFS) rate than those with no or minimal extension (P < 0.0001), there was no difference in the RFS rate between patients with no extension and those with minimal extension. Among patients with massive extension, the RFS rate tended to be worse in those with posterior extension than in those with anterior extension (P = 0.0562). Furthermore, the RFS rate of patients with massive posterior extension only to the recurrent nerve demonstrated a better RFS rate than those with extension to other posterior organs (P = 0.0052). Multivariate analysis demonstrated that massive extrathyroid extension is recognized as an independent prognostic factor for RFS (P = 0.0003). CONCLUSIONS: These findings suggest that (1) upgrading of T category for tumors with massive extension is appropriate, whereas that for tumors with only minimal extension is not, and (2) careful surgical treatment and postoperative follow-up are required for tumors with massive extension to posterior organs other than the recurrent laryngeal nerve.

Adenocarcinoma, Papillary↗

PubMed2006

Sensitivity and specificity of intraoperative recurrent laryngeal nerve stimulation test for predicting vocal cord palsy after thyroid surgery.

INTRODUCTION: Recurrent laryngeal nerve (RLN) palsy after thyroidectomy, although infrequently encountered, can decrease quality of life. In addition to the hoarseness that occurs with unilateral RLN palsy, bilateral RLN palsy leads to dyspnea and often to life-threatening glottal obstruction. Therefore, intraoperative awareness of the nerve's status is of great importance. This study examined the sensitivity and specificity of a palpation technique to detect contraction of the posterior cricoarytenoid muscle (PCA) through the posterior hypopharyngeal wall while the RLN was being stimulated with a disposable nerve stimulator during thyroid surgery (the laryngeal palpation test) to predict postoperative RLN deficits. METHODS: A total of 2197 RLNs in 1376 patients were identified to be at risk of injury during thyroidectomy performed between July 2003 and August 2004. Postoperative RLN integrity was assessed using direct laryngoscopy or laryngofiberoscopy to visualize vocal fold mobility. RESULTS: Altogether, 76 RLNs failed to elicit a PCA contraction in response to nerve stimulation, and 80 cases of temporary vocal cord palsy and 21 cases of permanent vocal cord palsy were recognized on postoperative evaluation. For postoperative vocal cord palsy, the sensitivity and specificity of the laryngeal palpation test were 69.3% and 99.7%, respectively, with a positive predictive value of 92.1% and negative predictive value of 98.5%. For permanent vocal cord palsy, the sensitivity and specificity were 85.7% and 97.3%, respectively, with a positive predictive value of 23.7% and negative predictive value of 99.8%. CONCLUSIONS: The laryngeal palpation test is not a particularly useful method for predicting the level of RLN function after thyroidectomy. All patients must be examined postoperatively by direct laryngoscopy or laryngofiberoscopy to check vocal cord mobility. Even if there is no contraction of the PCA and we detect vocal cord palsy immediately after surgery, vocal cord palsy often recovers within 1 year when visual preservation of RLN is successful.

Adolescent↗

PubMed2006

A prophylactic infusion of calcium solution reduces the risk of symptomatic hypocalcemia in patients after total thyroidectomy.

BACKGROUND: Several risk factors have been associated with post-operative transient hypocalcemia after thyroid surgery. However, there are no studies evaluating preventive measures to avoid symptomatic postoperative hypocalcemia. Although intravenous infusion of calcium improves hypocalcemic symptoms, it is unknown whether prophylactic infusion prevents symptoms of postoperative hypocalcemia. PATIENTS AND METHODS: Five hundred and forty-seven patients underwent total thyroidectomy. Two groups were identified: group A (n = 243) received prophylactic intravenous drip infusion of 78-156 mg of calcium solution at 3-8 hours after operation, and group B (n = 304) received no prophylactic treatment. Prophylactic infusion was used only once if the patients did not have symptoms of hypocalcemia. Serum calcium (Ca) levels, intact parathyroid hormone (i-PTH) levels on the first postoperative day (1st POD), and the prevalence of symptoms of hypocalcemia were prospectively analyzed. RESULTS: The serum Ca levels at the 1st POD in group A patients (7.91 +/- 0.49 mg/dl, mean +/- SD) was significantly higher than group B patients (7.65 +/- 0.54, P < 0.0001), while the serum i-PTH levels were not significantly different between the two groups. The prevalence of numbness and/or tetany before noon on the 1st POD was significantly lower in group A patients. Prophylactic infusion of calcium solution reduced the prevalence of tetany from 8.6% to 2.1%. CONCLUSION: A prophylactic infusion of calcium solution after total thyroidectomy may be useful in reducing the development of symptomatic hypocalcemia and reduces the patients' risk of having discomfort and anxiety due to hypocalcemia.

Calcium↗

PubMed2006

Clinical significance of lymph node metastasis of thyroid papillary carcinoma located in one lobe.

BACKGROUND: Previous studies have shown that lymph node metastasis can be of prognostic value. In this study, we investigated the clinical significance of node metastasis focusing on metastasis in the central compartment for patients with papillary carcinoma located in one lobe. PATIENTS AND METHODS: We investigated the frequency of lymph node metastasis in 759 patients with papillary carcinoma to determine whether and how such metastasis affects disease-free survival (DFS). RESULTS: Central node metastasis was observed in 63% of patients, and the frequency was increased in relation to tumor size. The frequency of lateral node metastasis was 62.0%, which was also directly related to tumor size. On multivariate analysis of cases showing tumor larger than 1 cm, central node metastasis was recognized as an independent prognostic factor of DFS. The frequency of metastasis to the paratracheal nodes contralateral to the tumor was drastically elevated for tumors larger than 1 cm, but metastasis to this region did not independently predict worse DFS. CONCLUSION: Central node metastasis independently predicts a worse DFS for patients with papillary carcinoma larger than 1 cm.

Adult↗

PubMed2006

Minimal extrathyroid extension does not affect the relapse-free survival of patients with papillary thyroid carcinoma measuring 4 cm or less over the age of 45 years.

PURPOSE: In the most recent version of the UICC TNM classification system for thyroid carcinoma, tumors with minimal extrathyroid extension were classified as T3. In this study, we investigated whether this upgrading is appropriate for papillary thyroid carcinoma. METHODS: We investigated the difference in the relapse-free survival (RFS) rate between patients with tumors having no, minimal, and massive extrathyroid extension in a series of 502 patients over the age of 45 years. RESULTS: Patients with tumors showing massive extension showed a worse RFS rate except for those with tumors measuring 1 cm or less. However, there was no significant difference in RFS between tumors measuring 4 cm or less showing no or minimal extension. In an investigation of 409 patients without any clinically apparent node metastasis, the RFS of patients with tumors larger than 4 cm with massive extension was significantly worse than those with tumors measuring 4 cm or less, while the RFS of patients with tumors with either no or minimal extension did not depend on the tumor size. CONCLUSIONS: These findings suggest that tumors with minimal extension should be classified to have the same T grade as those without such extension, and upstaging of such tumors is therefore not appropriate.

Aged↗

PubMed2006

Delta Np73 expression in thyroid neoplasms originating from follicular cells.

AIMS: p73, a homologue of p53, is known as a negative regulator of tumour progression. However, delta Np73, an isoform of p73 lacking the NH2-terminal transactivation domain plays an oncogenic role by interfering with the activity of p53 and TA (full-length transactivating isoforms) p73. In this study, we investigated the expression of delta Np73 in human thyroid neoplasms originating from follicular cells. METHODS: We immunohistochemically investigated delta Np73 expression in 223 thyroid neoplasms. Delta Np73 expression level was evaluated as the sum of positivity score and intensity score. RESULTS: Normal follicular cells did not express delta Np73, but 27.3% of follicular adenoma, 85.4% of follicular carcinoma, 99.2% of papillary carcinoma, and 95.7% of anaplastic carcinoma were positive for the transcript. Delta Np73 expression level did not differ between widely invasive and minimally invasive follicular carcinomas. In papillary carcinoma, the level was inversely linked to tumour size, extrathyroid extension, and clinically apparent metastasis. Furthermore, in anaplastic carcinoma, delta Np73 expression level was significantly lower than that in papillary carcinoma. CONCLUSIONS: Our findings indicate that delta Np73 plays a role predominantly in the early phase of papillary carcinoma progression.

Adenocarcinoma, Follicular↗

PubMed2006

Inverse relationships between the expression of MMP-7 and MMP-11 and predictors of poor prognosis of papillary thyroid carcinoma.

AIMS: Matrix metalloproteinases (MMPs) have various functions that play roles in carcinoma development. In this study, we investigated the expression of two representative MMPs, MMP-7 and MMP-11, in papillary thyroid carcinomas. METHODS: We immunohistochemically investigated the expression of these MMPs in 196 cases of papillary carcinoma. RESULTS: A high level of MMP-7 expression was observed in 56 cases (28.3%). The expression level was significantly decreased in cases showing large tumour, N positivity, large pT and poor differentiation. MMP-11 expression was high in 119 cases (60.1%). The expression level was inversely related to tumour size, N factor, pT factor, pN factor, extrathyroid extension, and poor differentiation. CONCLUSIONS: In contrast to other MMPs, MMP-7 and MMP-11 are inversely linked to aggressive characteristics of papillary thyroid carcinoma and their down-regulations may even be a marker of poor prognosis in patients.

Biomarkers, Tumor↗

PubMed2006

Coexistent Anaplastic and Differentiated Thyroid Carcinoma.

The aim of the present study was to clarify the underlying molecules that might contribute to the highly aggressive behavior of anaplastic thyroid carcinoma. We selected 5 cases of anaplastic thyroid carcinoma that had a differentiated area to determine differences in the molecules of undifferentiated and differentiated cancer cells. We immunohistochemically examined the localization of nuclear antigen (Ki-67), proliferating cell nuclear antigen (PCNA), p53, apoptotic protease-activating factor-1 (Apaf-1), CD26, galectin-3, E-cadherin, and CD147. We found an increased Ki-67, PCNA, and p53 labeling indices; decreased levels of Apaf-1, CD26, galectin-3, and E-cadherin; and overexpression of CD147 in the undifferentiated area compared with the differentiated area. These findings indicate high proliferative properties, suppression of apoptosis, disruption of cell-cell interaction, and induction of matrix metalloproteinases in the undifferentiated areas. Thus the molecules examined might be useful for evaluating the aggressive nature of this tumor and the prognosis.

Journal Article↗

PubMed2006

Thrombospondin 1 mRNA as a candidate for a marker to detect thyroid-derived fibroblasts in fine needle aspiration biopsy of the thyroid.

Possible interference of fibroblasts is suggested in aspiration biopsy nucleic acid diagnosis (ABND). However, detection of fibroblasts in the aspirates is difficult, because the gene expression profiles of thyroid malignancies and fibroblasts are much alike in many aspects. To identify a specific marker for thyroid-derived fibroblasts, the data of the serial analysis of gene expression (SAGE) were compared to screen differentially expressed genes between fibroblasts and thyroid normal and tumor tissues. In the SAGE data, 5 genes were identified to be differentially expressed. Among these, thrombospondin 1 (TSP-1, THBS1) mRNA was the most differentially expressed. Further, the overexpression of TSP-1 mRNA in fibroblasts was confirmed by real-time RT-PCR analysis using 73 thyroid normal and tumor tissues and 7 cultures of thyroid-derived fibroblasts. These results suggest that TSP-1 mRNA is a possible marker for contamination of thyroid-derived fibroblasts.

Biomarkers↗

PubMed2006

Coexistent anaplastic and differentiated thyroid carcinoma: an immunohistochemical study.

The aim of the present study was to clarify the underlying molecules that might contribute to the highly aggressive behavior of anaplastic thyroid carcinoma. We selected 5 cases of anaplastic thyroid carcinoma that had a differentiated area to determine differences in the molecules of undifferentiated and differentiated cancer cells. We immunohistochemically examined the localization of nuclear antigen (Ki-67), proliferating cell nuclear antigen (PCNA), p53, apoptotic protease-activating factor-1 (Apaf-1), CD26, galectin-3, E-cadherin, and CD147. We found increased Ki-67, PCNA, and p53 labeling indices; decreased levels of Apaf-1, CD26, galectin-3, and E-cadherin; and overexpression of CD147 in the undifferentiated area compared with the differentiated area. These findings indicate high proliferative properties, suppression of apoptosis, disruption of cell-cell interaction, and induction of matrix metalloproteinases in the undifferentiated areas. Thus the molecules examined might be useful for evaluating the aggressive nature of this tumor and the prognosis.

Biomarkers, Tumor↗

PubMed2005

Expression of cdc25B and cdc25A in medullary thyroid carcinoma: cdc25B expression level predicts a poor prognosis.

Cdc25B and cdc25A phosphatases are prominent stimulators of cell cycle progression and have been suggested to play oncogenic roles. In this study, we immunohistochemically investigated the expression of these phosphatases in medullary thyroid carcinoma. Cdc25B was positive in 35.8% of cases examined. Its positivity was linked only to patient age. However, patients with cdc25B-positive tumors showed a significantly worse disease-free survival rate (P=0.0210) than those with cdc25B-negative tumors. Cdc25A was positive in only 17.2% of cases and was not related to clinicopathological parameters or prognosis. These findings suggest that cdc25B can be regarded as having prognostic significance and as a novel marker of biologically aggressive characteristics in this carcinoma.

Adolescent↗