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Biomedical subjects

Kanji Kuma

Publications and source records attributed to Kanji Kuma.

At least 37 records · Page 2Linked to original sources

Papillary microcarcinomas of the thyroid with preoperatively detectable lymph node metastasis show significantly higher aggressive characteristics on immunohistochemical examination.

OBJECTIVES: We recently demonstrated that papillary microcarcinomas with preoperatively detectable node metastasis in the lateral compartment on ultrasonography (clinically apparent metastasis) show worse postoperative relapse-free survival than those with no metastasis or metastasis that could not be detected preoperatively, but was confirmed by pathological examination after surgery (occult metastasis). In this study, we investigated difference in the aggressive characteristics of microcarcinoma of this type from various perspectives. MATERIALS AND METHODS: We immunohistochemically examined the expression of cell proliferating markers, Ki-67, cyclin D1, p27, and retinoblastoma gene product (pRb), apoptotic markers, single-strand DNA (ssDNA), and metastatic suppressor, kangai-1 (KAI-1) for 19 microcarcinoma patients with clinically apparent metastasis, 14 patents with occult metastasis, and 22 patients without metastasis. RESULTS: Cases of clinically apparent metastasis showed increased cyclin D1 expression together with decreased p27 expression and higher levels of pRb and Ki-67 expression. Furthermore, ssDNA expression was higher and bcl-2 expression was lower in these cases, while KAI-1 expression was significantly reduced. There was no significant difference in the expression of these proteins between cases demonstrating no and occult metastases. CONCLUSION: These findings suggest that cases of clinically apparent metastasis show significantly higher growth based on cell proliferating activity, apoptosis, and expression of metastatic suppressor than those demonstrating no or occult metastases.

Adult↗

Thyrotoxicosis caused by weight-reducing herbal medicines.

The weight-reducing herbal medicines "Dream Shape" and "Ever Youth" became available in Japan in 2000. Herein, we describe 12 patients who developed thyrotoxicosis after taking them. The thyroid hormone content of 1 capsule or tablet of herbal medicine, measured following Pronase digestion and ethanol extraction, was approximately 1 mug of triiodothyronine and 3 to 4 mug of thyroxine. Two of us took 10 capsules or tablets of Dream Shape or Ever Youth, and changes in thyroid hormone levels were observed during the first 24 hours. Serum free triiodothyronine levels began to rise 2 hours after ingestion and reached peak levels at 4 to 8 hours; changes in free thyroxine and thyrotropin levels were small during the first 24 hours. Similar herbal medicines may have been distributed to other countries via the Internet. Resultant factitious thyrotoxicosis can create diagnostic and therapeutic confusion, particularly in patients with thyroid disease.

Administration, Oral↗

Phosphorylation and inactivation of Tob contributes to the progression of papillary carcinoma of the thyroid.

Tob, a member of the Tob/BTG family, is a novel anti-proliferative protein, but it becomes inactive when phosphorylated. In this study, we investigated whether Tob is phosphorylated and inactive in various thyroid neoplasms in order to elucidate how this event plays a role in their progression. Tob phosphorylation was only occasionally seen in normal follicular cells. A high level of Tob phosphorylation was observed in 42.1% of follicular adenoma, 14.3% of follicular carcinoma. In papillary carcinoma, the Tob phosphorylation level was elevated more frequently than that in follicular carcinoma, and 39.7% of specimens were classified in the high group. Tob phosphorylation level in papillary carcinoma was directly linked to tumor size, lymph node metastasis, extrathyroid extension and the presence of poorly differentiated lesion. In anaplastic carcinoma, surprisingly, Tob phosphorylation was not observed in any cases, but the deficiency of Tob expression was also observed in all these cases. These results suggest that (1) Tob phosphorylation contributes to the progression of papillary carcinoma especially in the later phase through cancellation of its anti-proliferative function, and (2) the deficiency of Tob expression is attributable to the lack of Tob phosphorylation in anaplastic carcinoma.

Adenoma↗

Decreased relative expression level of trefoil factor 3 mRNA to galectin-3 mRNA distinguishes thyroid follicular carcinoma from adenoma.

The expression level of trefoil factor 3 (TFF3) mRNA is a marker for distinguishing thyroid follicular adenomas from carcinomas. However, when measuring the expression level of TFF3 mRNA in fine needle aspiration biopsies, an appropriate internal control mRNA, of which expression is restricted in thyroid epithelial--derived cells, is necessary, since they are often contaminated with a considerable number of blood cells, which do not express TFF3 mRNA. In this study, we evaluated the efficiency of molecular-based diagnosis of thyroid follicular carcinoma by measuring the relative expression of TFF3 mRNA by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) using galectin-3 mRNA as an internal control. The TFF3/galectin-3 mRNA ratio (T/G ratio) was measured in 54 follicular adenomas and 29 follicular carcinomas. It was markedly decreased in 7 follicular carcinomas of widely invasive type and with evident distant metastases. When the cutoff point was set at 16.0 by a receiver operator characteristic curve, the TG ratio showed good agreement with the pathological diagnosis [kappa=0.55; 95% confidence interval (CI), 0.34-0.77]. This agreement was better when the pathologically questionable cases were excluded (kappa=0.72; 95% CI, 0.49-0.95). Quantification of the T/G ratio may be a useful tool for the distinction between follicular adenomas and carcinomas, which is the most difficult in thyroid pathology.

Adenocarcinoma, Follicular↗

Usefulness of thyroglobulin measurement in fine-needle aspiration biopsy specimens for diagnosing cervical lymph node metastasis in patients with papillary thyroid cancer.

The diagnosis of lymph node metastasis in patients with papillary thyroid cancer is an important factor when deciding to perform neck dissection at the initial surgery, as well as for evaluating the lymph node swelling after surgery. Ultrasound (US)-guided fine-needle aspiration biopsy cytology (FNAB-C) is the most useful technique for diagnosing lymph node metastasis. Recently, however, measurement of thyroglobulin in the wash-out of the needle (FNAB-Tg) has been proposed for early detection of neck lymph node metastasis in patients with differentiated thyroid cancer. The purpose of this study was to evaluate the usefulness of FNAB-Tg in detecting lymph node metastasis prior to initial or reoperative thyroid surgery. US-guided FNAB-C was performed on 129 enlarged lymph nodes of 111 patients before surgery. All of them were later histologically confirmed to contain metastasis. Immediately after obtaining an FNAB-C specimen, the needle was rinsed with 0.5 ml of normal saline solution, and the wash-out was subjected to measurement of the Tg level (FNAB-Tg). If the FNAB-Tg level was higher than the serum Tg of the patient, we diagnosed the lymph node as positive (metastatic lymph node). FNAB-Tg sensitivity was 81.4%, and FNAB-C sensitivity was 78.0%. Altogether, 4 (36.4%) of 11 cases judged "benign" and 6 (37.5%) of 16 cases judged "inadequate" by FNAB-C were positive by the FNAB-Tg measurement. Thyroglobulin measurement in fine-needle aspiration biopsy wash-out is thus a useful technique for diagnosing lymph node metastasis of papillary thyroid cancer.

Biopsy, Fine-Needle↗

Needle tract implantation of papillary thyroid carcinoma after fine-needle aspiration biopsy.

Although fine-needle aspiration biopsy (FNAB) is a useful tool for diagnosing thyroid carcinoma, there are some risks of complications. In this study, we investigated tumor implantation by FNAB of papillary carcinoma. We compared the characteristics of the main tumors and implanted tumors of patients showing FNAB implantations. Between 1990 and 2002, 4912 patients underwent FNAB and were diagnosed as having papillary carcinoma. We encountered 7 cases of needle tract implantation, which account only for 0.14%. We reviewed these 7 cases as well as 3 other patients who underwent FNAB in other hospitals. The intervals between FNAB and detection of the implanted tumor ranged from 2 to 131 months. For these 10 patients, the main tumors in 6 were diagnosed as poorly differentiated carcinoma, and 7 showed extrathyroid extension. Five showed the development of implanted tumor after comparatively shorter intervals (2-68 months), and we classified these as the short interval group. The remaining 5 were classified as the long interval group, because tumor development occurred after 87-131 months. All 5 cases in the short interval group involved preoperatively detectable lymph node metastasis; those in the long interval group did not. The MIB-1 labeling index of the implanted tumor was high in 4 cases in the short interval group, but it was low in all cases in the long interval group. The implanted tumors could be surgically removed without recurrence at the focal sites. These findings indicate that, although high growth activity in the metastatic lesions may be a risk factor of FNAB, inducing the growth of implanted tumors along the needle tract within a short interval after the procedure, FNAB remains the most useful technique for diagnosing thyroid carcinoma. The incidence of implantation was low, and when it did occur, the tumors could be surgically removed without recurrence.

Aged↗

Stretching exercises to reduce symptoms of postoperative neck discomfort after thyroid surgery: prospective randomized study.

Patients who undergo thyroid surgery frequently suffer from unpleasant symptoms such as a stretching, choking, or pressing feeling or discomfort in the neck for a long time. The usefulness of rehabilitation (i.e., a stretching exercise) for reducing these symptoms after surgery has never been studied. In the present study, attempts were made to evaluate the usefulness of the stretching exercise in reducing disagreeable postoperative symptoms in the patients who had undergone thyroid surgery. A total of 409 patients, including 234 thyroid cancer patients, were randomly divided into a stretching group (n = 204) and a control group (n = 205). Patients in the stretching group were instructed that the stretching exercise was to be performed three times a day beginning the morning following surgery. A questionnaire survey was performed before surgery and then 1 week, 1 month, 6 months, and 1 year after surgery. Total symptom scores obtained from the questionnaire survey from the control group and the stretching group were compared. The use of analgesics was also investigated. Postoperative neck symptoms declined gradually over the course of a year, and the total symptom scores were significantly (p < 0.001) lower in the stretching group than in the control group at all points throughout the year (1 week, 1 month, 6 months, and 1 year). The mean requirement for the use of analgesics during hospitalization was significantly (p < 0.0001) less in the stretching group (1.6 +/- 2.3 tablets, mean +/- SD) than in the control group (3.1 +/- 3.8 tablets). The stretching exercise had effectively reduced postoperative neck symptoms and also reduced the use of analgesics after thyroid surgery.

Adolescent↗

Ultrasonographically and anatomopathologically detectable node metastases in the lateral compartment as indicators of worse relapse-free survival in patients with papillary thyroid carcinoma.

The recent prevalence of ultrasonography has made it easier to detect lymph node metastasis in the lateral compartment of patients with thyroid carcinoma. In this study, we investigated the prognostic impact of lateral node metastasis preoperatively detectable by ultrasonography (US) and metastasis diagnosed by pathology examination but not detected on preoperative US [anatomopathologically (AP)-detectable metastasis] in 560 patients with papillary carcinoma >1 cm in diameter, who underwent thyroidectomy with modified radical neck dissection at our hospital. Patients with US-detectable metastasis (US+ patients) showed a significantly worse relapse-free survival (RFS) rate than those with no metastasis (US-/AP- patients) or AP-detectable metastasis (US-/AP+ patients) regardless of tumor size. Furthermore, the RFS of US-/AP+ patients with tumors >2 cm was worse than that of US-/AP- patients with tumors >2 cm or US-/AP+ patients with tumors measuring 1.1-2.0 cm. There was no significant difference in RFS between US-/AP+ and US-/AP- patients with tumors measuring 1.1-2.0 cm. These findings suggest that US-detectable lateral metastasis predicts a worse RFS for patients regardless of tumor size, and AP-detectable metastasis affects the RFS of patients with tumors >2 cm.

Adenocarcinoma, Papillary↗

Ill-defined edge on ultrasonographic examination can be a marker of aggressive characteristic of papillary thyroid microcarcinoma.

We have previously demonstrated that, although most papillary thyroid microcarcinomas (PMC) do not grow or grow only slowly, cases showing lateral node metastasis diagnosed by ultrasonography (US) show an aggressive characteristic associated with poor disease-free survival. In this study, we focused on two prominent U.S. features: tumor, edge definition and strong echoes. We investigated whether these findings reflect aggressive characteristics of PMC in a series of 155 cases. Poor edge definition was observed in 21.5% of patients, all of who showed worse disease-free survival (p = 0.0477) than those with a well-defined edge. Furthermore, this finding was directly linked to US-diagnosed lateral node metastasis (p = 0.0001). Strong echoes were observed in 63.9% of the cases, and fine strong echoes were seen in 25.2%. Cases demonstrating fine strong echoes tended to frequently show recurrence (p = 0.0902), and this finding was also significantly linked to US-diagnosed lateral node metastasis (p = 0.0494). These findings suggest that an ill-defined tumor edge is an important US feature of biologically aggressive PMC. We should carefully follow such patients, regardless of the therapeutic strategy, observation, or surgical treatment chosen.

Adenocarcinoma, Papillary↗

Favorable surgical results in 433 elderly patients with papillary thyroid cancer.

Papillary thyroid cancer (PTC) has a good prognosis among patients younger than 45 years old, but the prognosis in elder is worse and treatment strategy is not well established. We retrospectively analyzed the clinical features and outcomes of 433 patients with PTC aged 70 years or older. The patients consisted of three groups: group A (n = 327); patients receiving surgical treatment, group B (n = 51); patients with microcancer (maximal diameter, < or = 1.0 cm) who did not undergo surgical treatment, group C (n = 55); patients in whom surgery was contraindicated due to age, high surgical risk or complication by other illnesses. In group A, the mean tumor size was 2.6 +/- 1.5 cm, and 218 patients (66.7%) had pathologically confirmed lymph node metastasis; 110 patients (33.6%) had extrathyroidal invasion. The 5- and 10-year overall survival rates (OSR) in group A were 97.2% and 85%, respectively, which was significantly higher than the 5-year OSR in group C (62.6%). The 5- and 10-year disease-specific survival rates (DSSR) in group A were 98.5% and 91.3%, respectively, which was also significantly higher than the 5-year DSSR in group C (81.8%). Although the patients in group B did not receive any treatment, none of them demonstrated cause-specific death or progression of disease. Papillary thyroid cancer in elderly patients, except for microcancers, may be biologically aggressive. Thus surgery is recommended for these patients, if their general status is judged able to tolerate the stress of anesthesia and surgery.

Aged↗

Ultrasonography as a method of screening for tracheal invasion by papillary thyroid cancer.

PURPOSE: To assess the reliability of ultrasonography (US) for detecting tracheal invasion by papillary thyroid cancer (PTC). METHODS: We reviewed the clinical and surgical data of 509 patients who underwent surgery for primary PTC during 2003, after routine preoperative US. RESULTS: Ultrasonography showed possible tracheal invasion in 43 of the 509 patients. However, the US findings could not be evaluated in 32 patients because of high tumor calcification, a tumor diameter greater than 4 cm, or tumor extension inferior to the clavicle. We shaved the tracheal wall in 11 patients and resected the tracheal wall in 2 patients. The sensitivity of US for diagnosing of tracheal invasion was 91%, the specificity 93%, the predictive value of a positive test 25%, the predictive value of a negative test 99%, and the accuracy 93%. CONCLUSION: Ultrasonography is a useful method of screening for tracheal invasion. A negative sonogram is a reliable indicator of the absence of tracheal invasion, except when tumors are highly calcified or extend inferior to the clavicle.

Adenocarcinoma, Papillary↗

Caveolin-1 and 14-3-3 sigma expression in follicular variant of thyroid papillary carcinoma.

There are two prominent types of thyroid carcinoma, papillary carcinoma (PC) and follicular carcinoma (FC) arising from thyroid follicular cells, which have different biological characteristics. The follicular variant of papillary carcinoma (FVPC) has a structure similar to FC, although it is classified as a subtype of PC. We have previously demonstrated that caveolin-1, a major component of caveolae and an inhibitor of growth signal transduction, and 14-3-3 sigma, a regulator of the cell cycle and signal transduction, are frequently expressed in pure PC, but not in FC. In this study, we investigated these expressions in FVPC and FC. Caveolin-1 and 14-3-3 sigma were expressed in 96.2% and 92.3% of FVPC, respectively. However, almost all FC, with only a few exceptions, were negative for these findings, indicating that these proteins were more frequently expressed in FVPC than in FC (p < 0.0001). These findings suggest that caveolin-1 and 14-3-3 sigma positively or negatively regulate the development of FVPC but not that of FC, reflecting the difference of biological characteristics of these two types of carcinoma.

14-3-3 Proteins↗

S100A9 expression is significantly linked to dedifferentiation of thyroid carcinoma.

S100A9, a calcium-binding protein, is associated with myeloid cell differentiation and is expressed in some adenocarcinomas as well as in squamous epithelia and squamous cell carcinoma. In this study, we immunohistochemically investigated S100A9 expression in thyroid neoplasms. S100A9 was absent in normal follicles, follicular adenoma, and follicular and papillary carcinomas with conventional growth structures. In lesions showing a solid, trabecular, or scirrhous growth pattern, S100A9 immunoreacitivity was occasionally observed. One (5.9%) of the 17 follicular carcinomas and three (7.8%) of the 38 papillary carcinomas were regarded as positive for S100A9, but the positive cell areas always accounted for 5% or less. However, S100A9 was positive in all 19 undifferentiated carcinomas examined. Among them, the positive cell area was greater than 5% in 16 (84.2%), and greater than 25% in six (31.6%) cases. It is therefore suggested that S100A4 protein plays an important role in thyroid carcinoma dedifferentiation, and can be considered a novel characteristic of undifferentiated carcinoma.

Adenocarcinoma, Follicular↗

Expression of Jun activation domain-binding protein 1 and p27 (Kip1) in thyroid medullary carcinoma.

AIMS: p27 is a prominent regulator of cell proliferation by universally inhibiting the cell cycle, while Jun activation domain-binding protein 1 (Jab1), a multifunctional cell signaling protein, contributes to carcinoma progression by degrading p27. In this study, we investigated the expression of these proteins in medullary thyroid carcinoma. METHODS: We immunohistochemically examined Jab1 and p27 expression in 64 medullary thyroid carcinomas. RESULTS: Of the 64 cases examined, decreased p27 expression was observed in 38 cases (59.4%). The p27 expression level was inversely linked to tumour size as well as plasma calcitonin level. Jab1 expression level was generally high, and 46 cases (71.9%) were classified as overexpressing Jab1. The incidence was higher than those in papillary and follicular carcinomas, which were previously reported. Jab1 expression level was inversely linked to that of p27, and all five cases with only cytoplasmic but not nuclear staining of p27 overexpressed Jab1. CONCLUSIONS: These findings suggest that (1) decrease in p27 expression may contribute to local tumour growth; (2) Jab1 expression is related to the progression of medullary carcinoma by decreasing the amount of p27 in the cell and accelerating its degradation; and (3) Jab1 may play a more vital role in the pathogenesis of medullary carcinoma than papillary and follicular carcinomas.

Adult↗

Galectin-3 expression in follicular tumours: an immunohistochemical study of its use as a marker of follicular carcinoma.

AIMS: Galectin-3, a member of the beta-galactoside binding family of lectins, has been regarded as a useful tool for discriminating malignant tumours from benign nodules of the thyroid, including the distinction between follicular carcinoma and adenoma. However, there are follicular tumours with unclear vascular or capsular invasion, which makes diagnosis more difficult. In this study, we investigated the relationship between galectin-3 expression and the degree of vascular or capsular invasion of follicular tumours. METHODS: We immunohistochemically investigated galectin-3 expression in 260 cases of follicular tumour with various degrees of vascular or capsular invasion classified into four categories. RESULTS: The galectin-3 expression level significantly increased with the degree of vascular or capsular invasion (p<0.0001). However, its diagnostic value for follicular carcinoma was not high because the sensitivity and specificity were 68.7% and 57.5%, respectively. CONCLUSIONS: Our findings suggest that galectin-3 plays a role in the transformation of follicular tumours from benign to malignant; however, when diagnosing follicular tumours, the presence of this protein should not be required for diagnosing malignant transformation in all cases. Therefore, we must conclude that galectin-3 should only be considered an adjuvant marker for follicular carcinoma.

Adenocarcinoma, Follicular↗

Acute suppurative thyroiditis after fine-needle aspiration causing thyrotoxicosis.

A case of thyrotoxicosis caused by acute suppurative thyroiditis after repeated fine-needle aspiration (FNA) is described. A 39-year-old woman with atopic dermatitis showed rapid enlargement of a left thyroid cyst after a third FNA. She had a high fever, painful swelling of the left thyroid, and elevated thyroid hormone levels. Ultrasonography revealed abscess formation in the left thyroid cyst. The cytologic examination of an FNA specimen showed abundant neutrophils, and culture of the aspirate yielded Staphylococcus aureus. Because antibiotic treatment for 1 month failed to improve the inflammatory findings, the patient subsequently underwent left thyroid lobectomy, which resulted in the normalization of thyroid function and the resolution of inflammation. Thyroid infection had possibly been induced by needle-track seeding, because atopic skin favors colonization by S. aureus because of local immunologic deficiency. FNA is a useful and safe technique for aspirating fluid from thyroid cysts, but special care is required in patients with atopic dermatatis to avoid bacterial infection.

Adult↗

Successful use of iodine and levothyroxine to treat Graves' disease in a pregnant patient with allergy to antithyroid drugs and high thyrotropin-binding inhibitor immunoglobulin after radioiodine therapy.

High titer of thyrotropin-binding inhibitor immunoglobulin (TBII) in patients with Graves' disease can cause fetal hyperthyroidism during pregnancy. Prevention of fetal hyperthyroidism by administration of antithyroid drug (ATD) and levothyroxine (LT(4)) to pregnant patients who previously received ablative therapy has been reported. We administered iodine and LT(4) to a patient during gestation, because she had a severe adverse reaction to ATD. Although gestation proceeded normally, the infant showed transient neonatal hyperthyroidism right after birth. We believe that the fetus would have developed hyperthyroidism if we had not administered iodine to the mother. Administration of iodine and LT(4) to a pregnant patient with Graves' disease showing a high TBII after ablative therapy should be considered in rare patients with allergy to ATD.

Adult↗