Biomedical subjects

Keiichi Nakano

Publications and source records attributed to Keiichi Nakano.

16 recordsLinked to original sources

PubMed2004

Prognosis after reoperation for local recurrence of papillary thyroid carcinoma.

PURPOSE: To investigate the factors associated with a favorable prognosis after reoperation for local recurrent papillary thyroid carcinoma (PTC), we reviewed 45 patients who underwent surgery for first local recurrence of PTC. METHODS: We divided the patients into two groups. Group A (n = 28) had no second recurrence, and group B (n = 17) had second local recurrence after surgery for recurrence. RESULTS: The mean follow-up period after reoperation was 56.9 months. The mean age at the time of reoperation in group A was significantly lower than that in group B, at 48.1 years versus 62.3 years, respectively (P = 0.0007). The mean age at the time of the initial operation in group A was also significantly lower than that in group B, at 40.1 years versus 55.1 years, respectively (P = 0.0006). Patients with recurrent tumors only outside the area dissected at the initial operation (n = 27) had a better outcome than those with recurrence within the dissected area (n = 18; P = 0.0127). Patients who underwent systematic partial or modified neck dissection (n = 36) had a better outcome than those who underwent only simple local resection (n = 9; P = 0.0169). CONCLUSION: For local recurrent PTC, systematic neck dissection is recommended over local resection of recurrent tumors.

Adult↗

PubMed2003

Expression of alpha1,6-fucosyltransferase (FUT8) in papillary carcinoma of the thyroid: its linkage to biological aggressiveness and anaplastic transformation.

Previous studies have demonstrated that terminal fucosylation is associated with the biological aggressiveness of carcinomas, but the significance of core fucosylation (alpha1,6-fucosylation) through alpha1,6-fucosyltransferase (FUT8) has not been studied in depth. Herein, we investigated the expression of alpha1,6-fucosyltransferase (FUT8) in 133 cases of thyroid carcinomas using an immunohistochemical approach. The expression of FUT8 was quite low in normal follicules. A high expression of FUT8 was observed in 33.3% of papillary carcinoma and the incidence was directly linked to tumor size and lymph node metastasis. In contrast, this phenomenon was less frequently observed in follicular carcinoma and anaplastic (undifferentiated) carcinoma. These results suggest that FUT8 expression may be a key factor in the progression of thyroid papillary carcinomas, but not follicular carcinomas, and decreases in FUT8 expression might be linked to anaplastic transformation.

Carcinoma↗

PubMed2003

p130 expression in thyroid neoplasms: its linkage with tumor size and dedifferentiation.

p130 belongs to the retinoblastoma-related gene family, and its gene product works to negatively regulate cell cycle progression in the G1 phase. In this study, we investigated p130 expression in thyroid neoplasms. p130 overexpression was observed in 33.3% of follicular adenoma and 50% of follicular carcinoma and the incidences were not significantly different. In papillary carcinoma, it was overexpressed in 36.5% of cases, but in microcarcinoma, the incidence was significantly lower (14.3%). Furthermore, in anapalstic carcinoma, p130 overexpression was less frequently seen than in papillary carcinoma except for microcarcinoma and follicular carcinoma, and only 14.3% of cases overexpressed this protein. These findings suggest that: (1) reduced p130 expression may contribute to the aggressive character of anplastic carcinoma; and (2) p130 may specify the growth characteristics of microcarcinoma.

Carcinoma↗

PubMed2003

Encapsulated anaplastic thyroid carcinoma without invasive phenotype with favorable prognosis: report of a case.

We herein report a case of anaplastic thyroid carcinoma in a 77-year-old woman with long-term disease-free survival. The tumor measured 7.5 x 6.0 cm in size and was diagnosed to be anaplastic carcinoma. We investigated the biological aggressiveness of this carcinoma by means of immunohistochemistry and found it have a high cell-proliferating activity, a disruption in the mechanism of apoptosis, and a high potential of cell spreading, similar to that observed in usual anaplastic carcinomas. The only unique point was that this tumor was encapsulated and no invasion of carcinoma cells beyond the capsule was microscopically observed. To avoid an obstruction of the trachea, a lobectomy without lymph node dissection was performed as a "palliative operation." Although neither adjuvant chemotherapy nor radiotherapy was carried out due to her age, she has nevertheless survived with no evidence of recurrence for 57 months after surgery. The presence of such a type of anaplastic carcinoma should thus be noted by surgeons and pathologists, even though the occurrence of such cases seems to be very rare.

Aged↗

PubMed2003

Y-box binding protein expression in thyroid neoplasms: its linkage with anaplastic transformation.

Recent studies have demonstrated that Y-box binding protein (YB-1) regulates the transcription of genes linked to carcinoma progression. In this study, we investigated the expression of this protein in thyroid neoplasms to elucidate its significance. The expression of YB-1 was immunohistochemically investigated using the monoclonal antibody for various thyroid neoplasms. Normal follicles did not overexpress YB-1, and only moderate overexpression of YB-1 was observed in some follicular tumors and papillary carcinoma, especially those of a larger size. In contrast, 92.9% of anaplastic carcinoma strongly overexpressed YB-1. YB-1 immunoreactivity was seen in both cytoplasms and cell nuclei, but the former was more predominant. These findings suggest that YB-1 plays a role in regulating the transcription as well as translation of genes contributing to the anaplastic transformation of thyroid carcinoma.

Adenocarcinoma, Follicular↗

PubMed2003

KAI1 expression in thyroid neoplasms: its linkage with clinicopathologic features in papillary carcinoma.

KAI1 is a metastasis suppressor gene located on human chromosome 11p11.2. Previous studies have shown that the down-regulation of KAI1 mRNA and decreased expression of its gene product are significantly linked to carcinoma progression, including metastatic ability. In this study, we investigated KAI1 protein expression in thyroid neoplasms. KAI1 overexpression was observed in 64.0% of papillary carcinoma cases, and the incidence was significantly higher than in cases of follicular carcinoma (20.0%) (p = 0.0001). In papillary carcinomas, decreased KAI1 expression was frequently observed in cases invading beyond the thyroid capsule (p = 0.001), as well as in lymph node metastases (p = 0.0047) and poorly differentiated lesions (p = 0.0299). Furthermore, in anaplastic carcinoma, the incidence of KAI1 overexpression was lower than in papillary carcinoma (p < 0.0001), and only 4.2% of the cases overexpressed this gene. These results suggest that KAI1 down-regulation is significantly related to the progression of papillary carcinoma, including lymph node metastasis, and its anaplastic transformation.

Adenocarcinoma, Follicular↗

PubMed2003

An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid.

The recent prevalence of ultrasound-guided fine-needle aspiration biopsy has resulted in a marked increase in the number of patients with papillary microcarcinoma (maximum diameter, </= 10 mm) of the thyroid detected by this sophisticated tool. On the other hand, it is debatable whether patients with papillary microcarcinoma should always undergo surgery after diagnosis, because a high incidence of occult papillary carcinoma has been observed in autopsy studies. Thus, we proposed observation without surgical therapy as a treatment option in 732 patients diagnosed with papillary microcarcinoma by the above technique from 1993 to 2001. One hundred sixty-two patients chose observation and were classified as the observation group. During the follow-up period for patients in the observation group, more than 70% of tumors either did not change or decreased in size compared to their initial size at diagnosis. They enlarged by more than 10 mm in 10.2%, and lymph node metastasis in the lateral compartments appeared in only 1.2% of patients during follow-up. On the other hand, 570 patients chose surgical treatment at diagnosis and 56 patients in the observation group who underwent surgery after a period of follow-up were classified as the surgical treatment group. Of these 626 patients, lymph node dissection was performed in 594 patients, and metastasis was confirmed histologically in 50.5%. Multiple tumor formation was seen in 42.8% of patients. In this group, the rate of recurrence was 2.7% at 5 years and 5.0% at 8 years after surgery. Our preliminary data suggest that papillary microcarcinomas do not frequently become clinically apparent, and that patients can choose observation while their tumors are not progressing, although they are pathologically multifocal and involve lymph nodes in high incidence.

Adolescent↗

PubMed2003

Overexpression of human tumor-associated antigen, RCAS1, is significantly linked to dedifferentiation of thyroid carcinoma.

OBJECTIVE: Counterattack by RCAS1 on carcinoma to cytotoxic T cells and natural killer (NK) cells has been suggested as a contribution to carcinoma progression, because RCAS1 can inhibit their proliferation and induce apoptosis. In this study, we examined RCAS1 expression in various thyroid neoplasms in order to clarify its clinical significance. METHODS: We studied RCAS1 expression by means of immunohistochemistry using a mouse monoclonal antibody against RCAS1 for normal thyroid epithelium, follicular adenoma, follicular carcinoma, papillary carcinoma and undifferentiated (anaplastic) carcinoma. RESULTS: Normal epithelium and follicular adenoma did not express or only faintly expressed RCAS1. In thyroid carcinomas. RCAS1 overexpression was more frequently observed in anaplastic (undifferentiated) carcinomas than papillary (p < 0.0001) and follicular carcinomas (p = 0.0018). In follicular carcinoma, the widely invasive type more frequently overexpressed RCAS1 than the minimally invasive type (p = 0.0488). Furthermore, the incidences of RCAS1 overexpression increased with carcinoma dedifferentiation (p < 0.0001). CONCLUSION: These results suggest that RCAS1 may contribute to the progression of thyroid carcinoma with high biological aggressiveness.

Adenocarcinoma, Follicular↗

PubMed2003

Changes in serum TSH receptor antibody (TRAb) values in patients with Graves' disease after total or subtotal thyroidectomy.

TSH receptor antibodies (TRAb) are generally regarded as mediators of thyroid stimulation in Graves' disease. In addition, a high serum TRAb value during pregnancy is one of the risk factors for intrauterine death, prematurity, and fetal or neonatal hyperthyroidism. Recently, correlations between a high serum TRAb value and endocrine opthalmopathy were also suggested. Surgical resection of the thyroid is usually followed by a reduction of serum TRAb levels in variable degrees. The relation between the extent of the thyroidectomy and the degree of reduction is still controversial. In addition, the changes in the TRAb value after total thyroidectomy (TT) over a long period of time have never been studied. We studied the changes in serum TRAb values after TT and subtotal thyroidectomy (ST) for more than 7 years. Forty-one patients with Graves' disease underwent TT, and 99 patients underwent ST. The serum TRAb values and the ratio of the patients who achieved normal values among each group (normalization rates of TRAb) at 3 and 6 months, 1, 3, 5 and 7 years after surgery were compared between the TT group and ST group. The mean preoperative TRAb values were not significantly different between the TT and ST groups, and the mean TRAb values measured 3, 6 and 12 months after surgery were not significantly different between the groups. However, the TRAb values measured 3, 5 and 7 years after surgery were significantly (p<0.05) lower in the TT group than in the ST group (16.7 +/- 3.3% vs 28.0 +/- 2.6%, 12.6 +/- 3.4% vs 29.3 +/- 3.8%, 5.6 +/- 0.9% vs 25.4 +/- 4.1%, respectively). The normalization rates of TRAb were not significantly different between the groups until 1 year after surgery. However, the normalization rates 3, 5 and 7 years after surgery were significantly (p<0.05) higher in the TT group than in the ST group (65.7% vs 42.4%, 77.3% vs 46.7%, 100% vs 59.1%, respectively). The surgical complication rates of TT were similar to ST except for permanent hypoparathyroidism. TT is a treatment option for Graves' disease, especially in patients with a high TRAb value who wish to have children or who have Graves' opthalmopathy.

Adolescent↗

PubMed2002

Prospective trial of unilateral surgery for nonhereditary medullary thyroid carcinoma in patients without germline RET mutations.

Although sporadic medullary thyroid carcinoma (MTC) tends to be unicentric and confined to one lobe, total thyroidectomy is usually performed because of the risk of a hereditary or bilateral process. Germline RET mutation analysis can discriminate hereditary MTC and truly sporadic, nonhereditary MTC. We analyzed 72 of 94 patients with MTC to establish the genetic nature and the clinical features of nonhereditary MTC. Since 1996 we have prospectively treated 15 patients with nonhereditary MTC (prospective study group, or PSG) according to a unilateral surgery policy. A group of 22 previously operated patients in whom the nonhereditary nature was established served as controls (retrospective study group, or RSG). Systematic central and ipsilateral neck dissection was performed in both groups. Outcome was assessed using postoperative stimulated serum calcitonin levels; a normal value was considered a biochemical cure. All 24 hereditary MTC patients carried germline RET mutations: 8 of 48 patients with apparently sporadic MTC had the mutations, and 6 of the 8 had bilateral MTC. All 40 patients without mutations had a unilateral tumor. In the RSG group 15 of 22 (68%) patients underwent total thyroidectomy, and the biochemical cure rate was 68%. Although only 3 of 15 (20%) of the PSG patients underwent total thyroidectomy, 12 of the 15 (80%) achieved biochemical cure. Univariate analyses revealed that pathologic node involvement- high T and N stages-was adversely related to biochemical cure. The extent of thyroid resection was not related to biochemical cure. Of 20 patients with node involvement, 10 achieved biochemical cure, indicating the importance of systematic neck dissection. Hemithyroidectomy with systematic central and ipsilateral neck dissection is appropriate surgery for nonhereditary MTC.

Adult↗

PubMed2002

Expression of G2-M modulators in thyroid neoplasms: correlation of cyclin A, B1 and cdc2 with differentiation.

Previous studies have demonstrated that cell proliferating activity accurately reflects the biological aggressiveness of thyroid neoplasms. In this study, we focused on the G2-M boundary regulators of the cell cycle and investigated the expression of three proteins, cyclin A, cyclin B1 and cdc2. The incidence of cyclin A overexpression was significantly linked to carcinoma differentiation (p < 0.0001) and, in particular, all 21 cases of undifferentiated carcinoma overexpressed this protein. On the other hand, cyclin B1 was overexpressed in four undifferentiated carcinomas (19.0%), but not in carcinomas of other types. Cdc2 overexpression was also related to carcinoma differentiation (p < 0.0001), and was directly linked to cyclin A overexpression (p < 0.0001), but not to cyclin B1 overexpression. No significant relationship could be established between the overexpression of these proteins and the histological type of follicular tumor. These results suggest that cyclin A, rather than cyclin B1, contributes significantly to the aggressive character of thyroid carcinoma, together with cdc2.

Adenoma↗

PubMed2002

Expression of p57/Kip2 protein in normal and neoplastic thyroid tissues.

p57 (Kip2) belongs to the Cip/Kip family and is one of the universal negative regulators of the cell cycle. In this study, we investigated the p57 expression of various types of thyroid neoplasm. p57 overexpression was observed in only 4.2% of normal thyroid tissues. In follicular adenoma and minimally invasive follicular carcinoma, p57 was overexpressed in 100% and 91.7% of the cases, respectively. However, its incidence was significantly lower (p<0.0001) in widely invasive follicular carcinoma, of which only 36.4% overexpressed p57. This phenomenon was seen in 63.1% of papillary carcinoma and 13.3% of anaplastic (undifferentiated) carcinoma. Furthermore, poorly differentiated and undifferentiated carcinoma more frequently lacked p57 expression (p<0.0001). These results suggest that the down-regulation of p57 may play a role in the dedifferentiation of thyroid carcinoma and in follicular carcinoma mutating to be more invasive.

Cell Differentiation↗

PubMedDate not supplied

Bag-1 expression in thyroid neoplasm: its correlation with Bcl-2 expression and carcinoma dedifferentiation.

BACKGROUND: Apoptosis, programmed cell death, is one of the promnent factors in the evaluation of carcinoma characteristics. It is well-known that bcl-2 and its related proteins significantly modulate apoptosis. Bag-1 is a recently identified bcl-2-related protein and is known to be linked to the biological aggressiveness of some carcinomas. MATERIALS AND METHODS: We immunohistochemically investigated bag-1 and bcl-2 expression in various thyroid neoplasms using monoclonal antibodies. RESULTS: High bag-1 expression was observed in 66.7% of follicular adenoma and 75.0% of follicular carcinoma, and no statistical difference was established between them. In papillary carcinoma, 60.7% were classified with high bag-1 expression, whereas only 4.5% of anaplastic (undifferentiated) carcinoma highly expressed bag-1, and the incidence was significantly lower (p < 0.0001) than in papillary and follicular carcinomas. Furthermore, in thyroid neoplasm, bag-1 expression was directly linked (p < 0.0001) to bcl-2 expression. CONCLUSION: These findings suggest that bag-1 may interact with bcl-2 to play an important role in thyroid neoplasm before anaplastic transformation, and the disruption of events mediated by bag-1 and bcl-2 may be a typical characteristic of undifferentiated carcinoma.

Adenocarcinoma, Follicular↗

PubMedDate not supplied

Survivin expression is significantly linked to the dedifferentiation of thyroid carcinoma.

Survivin is a novel member of the apoptosis protein inhibitors, but according to previous reports, it is also significantly linked to cell proliferating activity. In this study, we investigated the expression of survivin in thyroid neoplasms. Survivin was only occasionally expressed in normal follicular cells, whereas in follicular and papillary carcinomas, about 20% of cases were positive for survivin. The incidence was significantly higher in advanced stage papillary carcinoma (p=0.0080) and papillary and follicular carcinomas with poorly differentiated lesions (p=0.0150). In anaplastic carcinoma, survivin positivity was observed in 84% of the cases, which was in significantly higher incidence than in papillary or follicular carcinoma (p<0.0001). These results suggest that survivin is strongly related to the dedifferentiation of thyroid carcinoma.

Adenocarcinoma, Follicular↗

PubMedDate not supplied

Decreased expression of cyclin G2 is significantly linked to the malignant transformation of papillary carcinoma of the thyroid.

BACKGROUND: Cyclin G2 is a novel cyclin negatively regulating the cell cycle progression, contrary to the characteristics of conventional cyclins. However, little is known about the cyclin G2 expression in human carcinomas. We thus investigated cyclin G2 expression in human thyroid neoplasms. MATERIALS AND METHODS: We immunohistochemically examined cyclin G2 expression in 40 normal thyroids and 80 thyroid neoplasms. RESULTS: Normal thyroids expressed cyclin G2 in more than 5% of follicular cells. Of 30 papillary carcinomas including 6 microcarcinoma, cyclin G2 expression was not, or only occasionally, observed in carcinoma cells, indicating its expression decreased in all these cases. On the other hand, in 16 of the 24 follicular adenomas (66.7%) and 5 of the 23 follicular carcinomas (21.7%), cyclin G2 expression was retained (more than 5% of neoplastic cells were positive), and adenomas more frequently (p = 0.0032) retained cyclin G2 expression than carcinomas. CONCLUSION: Our results suggest that lack of cyclin G2 plays an important role in the malignant transformation of papillary carcinoma. Also, it may play an adjuvant role in the transformation of follicular adenoma to carcinoma. This is the first study of the expression of cyclin G2, a novel cyclin having a role opposite to that of conventional cyclins, in human carcinoma.

Carcinoma↗

PubMedDate not supplied

Alterations of the K-ras and p53 genes and microsatellite instability in sporadic colorectal carcinomas.

BACKGROUND: The international guidelines for the evaluation of microsatellite instability (MSI) in colorectal cancer were defined in 1997 by the National Cancer Institute (NCI). Here, the relationship between MSI, cancer-associated genes and their clinicopathological variables were revaluated using these guidelines. PATIENTS AND METHODS: Mutations of K-ras at exon 1 and p53 at exons 5, 6, 7 and 8 were analyzed in 43 cases of sporadic colorectal carcinoma. MSI was analyzed using the 5 markers recommended by the NCI reference panel. RESULTS: The proportion of p53 mutations in the MSI-H cases (0 out of 5; 0%) was lower than that of non-MSI-H cases (23 out of 38; 60.5%) (p=0.0117). The proportion of p53 mutations in microsatellite stable (MSS) cases (21 out of 34; 61.8%) was higher than that of non-MSS cases (2 out of 9; 22.2%) (p=0.0366). The proportion of K-ras mutations in MSI-H tumors (1 out of 5; 20.0%) was less frequent than in non-MSI-H tumors (19 out of 38; 50.0%) (p=0.2115). CONCLUSION: p53 mutations in MSI-H tumors were much less common than in non-MSI-H tumors. This result suggested that alterations of the p53 gene are not closely associated with carcinogenesis in MSI-H carcinomas.

Aged↗