Hitoshi Kawamoto

Extracapsular invasion of lymph node metastasis is an indicator of distant metastasis and poor prognosis in patients with thyroid papillary carcinoma

In patients with thyroid papillary carcinoma, age and the presence or absence of distant metastasis are regarded as the main prognostic factors. However, the histologic characteristics of thyroid papillary carcinoma that develops distant metastasis have not yet been clarified.

Familial nonmedullary thyroid carcinoma characterized by multifocality and a high recurrence rate in a large study population.

First-degree relatives of persons with thyroid cancer are known to be at relatively high risk for the disease. To better understand the clinicopathologic characteristics of familial nonmedullary thyroid carcinoma (FNMTC), we carried out a retrospective study in which we identified individuals treated at our institution who had at least one first-degree relative with the disease. We used data obtained from our patient records to compare the features of 258 cases of the disease with the features of sporadic papillary or follicular thyroid carcinoma in another group of patients. The 258 patients represented 154 families and were selected from among 6458 patients with papillary or follicular thyroid carcinoma who underwent thyroidectomy between 1946 and 2000. Compared to the patients with sporadic disease, the FNMTC patients were more likely to have intraglandular dissemination (28.5% vs. 40.7%; p < 0.0001) and multiple benign nodules (29.8% vs. 41.5%; p <0.0001). There were no significant differences between the two types of patients in terms of gender, age, tumor diameter, adhesion to or invasion of the surrounding tissues, macroscopic metastasis observed at surgery, histology, presence of single benign nodules, presence of chronic thyroiditis, microscopic metastasis, or rate of lymph node metastasis. Recurrence was statistically frequent in the FNMTC patients compared with that in the sporadic disease patients (16.3% vs. 9.6%; p = 0.0005), and the disease-free survival rate was significantly poorer in the FNMTC patients (p = 0.0041 by the Wilcoxon test and p <0.0001 by the log-rank test). No significant difference in the overall survival rate was found between the two groups. Multivariate analysis by Cox’s proportional hazards method showed FNMTC to be an independent predictor of shorter disease-free survival (risk ratio 1.88; confidence interval 1.35–2.54; p = 0.0003). Locoregional recurrence in the ipsilateral or contralateral lymph nodes and contralateral thyroid lobe was significantly more frequent in the FNMTC patients than in the sporadic disease patients, whereas no difference was found regarding distant metastases. We conclude that FNMTC is a clinically distinct entity with an aggressive nature. Because of the frequent presence of benign nodules, multifocality, and high rate of locoregional recurrence, total or near-total thyroidectomy with modified radical neck dissection in FNMTC patients is recommended.

Trans-sellar color Doppler ultrasonography during transsphenoidal surgery.

OBJECTIVE To improve the safety and efficacy of transsphenoidal pituitary adenoma surgery, we investigated transsphenoidal intraoperative color Doppler ultrasonography using a biplane transducer system. METHODS We studied 23 patients with pituitary adenomas (18 patients with macroadenomas and 5 patients with microadenomas) who underwent transsphenoidal surgery. The Hitachi EUB555 color Doppler ultrasound system (Hitachi Medical, Tokyo, Japan) was used with a pediatric biplane transesophageal echo cardiography probe (EUP-ES533, 7.5 MHz, biplane phased array sector probe, 9.8-mm tip). The probe was inserted into the saline-filled sphenoid sinus after the sellar floor was opened. Intra- and suprasellar images were obtained just before dural incision and after the tumor removal was thought to have been accomplished. RESULTS In all patients, the tumor was depicted as a slightly hyperechoic mass, as compared with the cerebrum. Using color Doppler imaging, major cerebral arteries were depicted clearly in 74% of patients. The pituitary glands, pituitary stalks, and optic chiasms were observed in patients with small adenomas, but not when large adenomas were present. Cavernous sinus invasion, concomitant aneurysm, and residual tumor were clearly visualized. In patients with large adenomas, the end point of surgery was decided when there was an ultrasonographically demonstrated collapsed tumor capsule, subcapsular total vacancy, and reappearance of the optic chiasm. CONCLUSION Trans-sellar color Doppler ultrasonography seems to be a useful intraoperative guiding system that may improve the safety and efficacy of transsphenoidal surgery.

Thyroid Cancer Associated with Adenomatous Goiter: An Analysis of the Incidence and Clinical Factors

We evaluated the incidence of thyroid cancer in patients with adenomatous goiter and investigated the clinical factors distinguishing patients with occult thyroid cancer, defined as a tumor size smaller than or equal to 10 mm, from those with clinical thyroid cancer, defined as a tumor size larger than 10 mm. Of 835 patients with histologically confirmed adenomatous goiter, 256 (30.7%) also had thyroid cancer, being occult in 137 patients and clinical in 119 patients. There was no correlation between the maximum size of the thyroid cancer tumor and the age of the patient, and the percentage of patients with thyroid cancer in each group was not influenced by age. There were no significant differences in age, sex, the serum concentrations of free triiodothyronine, free thyroxine, thyrotropin, and thyroglobulin, or the urinary iodine creatinine ratio. The frequency of calcified lesions being detected by ultrasonography (US) and/or neck X-ray in the patients with clinical thyroid cancer was significantly greater than that in those with occult cancer at 83%vs 57%, respectively (P<0.0001). This study disclosed a high prevalence of thyroid cancer associated with adenomatous goiter, and the results suggest that a considerable number of associated carcinomas remain occult. The detection of calcification in the thyroid gland is one of the surgical indications for patients with adenomatous goiter.

Type IV collagenase activity and cavernous sinus invasion in human pituitary adenomas

SummaryPituitary adenomas are regarded generally as benign tumours, but some of them can invade the cavernous sinus. On the other hand, matrix metalloproteinase-9 (MMP-9), which is a type IV collagenase, recently has been found to be expressed in matastases and to be related to the invasiveness of various malignant tumours including brain tumours. In order to investigate some characteristic features of pituitary adenomas which invade the cavernous sinus, we examined immunohistological studies for MMP-9 in seven pituitary adenomas for type IV collagen in a dura mater and assayed for type IV collagenase activity in seven adenomas using type IV collagen labelled with fluorescein isothiocyaniate (FITC).We found immunopositive adenoma cells for MMP-9 in all invasive adenoma and immunopositive spindle like cells for type IV collagen in the dura mater. All three invasive adenomas had high levels of type IV collagenase activity (0.57–0.72 U/ml), but the four adenomas which did not invade the cavernous sinus had low levels of type IV collagenase activity (0.0–0.10 U/ml).These results suggest that the level of type IV collagenase activity in a pituitary adenoma may be related to its ability to invade the cavernous sinus.

Effect of Combining Ultrasonography and Ultrasound-Guided Fine-Needle Aspiration Biopsy Findings for the Diagnosis of Thyroid Nodules

OBJECTIVE To assess the accuracy of ultrasonography and cytology in predicting malignancy in thyroid nodules. DESIGN Prospective open study. SETTING Thyroid centre, Japan. SUBJECTS 329 nodules in 309 patients examined by a new ultrasound scanner and ultrasound-guided fine-needle aspiration biopsy. INTERVENTIONS Comparison of ultrasonographic, cytological, and combined diagnosis with the histological diagnosis. MAIN OUTCOME MEASURES Sensitivity, specificity, and accuracy of each diagnostic method. RESULTS The sensitivity, specificity, accuracy were 84%, 87%, 85% for cytological diagnosis, and 82%, 91%, and 87% for ultrasonographic diagnosis. By using ultrasonographic diagnosis when cytological specimens were inadequate or gave false negative results, the sensitivity, specificity, and accuracy went up to 89%, 91%, and 90%, respectively. We could not diagnose follicular carcinomas accurately by combined cytology and ultrasonography. CONCLUSION The combination of ultrasonography and cytology improves the accuracy of diagnosis of thyroid nodules, but is less effective with follicular tumours.

Analysis of the growth rate and cavernous sinus invasion of pituitary adenomas

SummaryPituitary adenomas generally are regarded as benign tumours, but a part of them can invade the cavernous sinus and recur. We examined 43 pituitary adenomas for the following factors: tumour volume, endocrinological function, cavernous sinus invasion, and growth rates examined by using anti-proliferating cell nuclear antigen (PCNA) and MIB1 (a novel anti-Ki-67) as markers.There was significant correlation between PCNA- and MIB1-positive cell rates and PCNA- and MIB1-positive cell rates were higher in the three cases with rapid regrowth than in the other cases. Staining was stronger and more distinct for MIB1 than for anti-PCNA; thus, MIB1-positive cells were easily distinguished by their intense immunoreactivity. MIB1 may be useful for detecting those rare cases with rapid regrowth even when initially regarded as benign tumours.Adenomas with cavernous sinus invasion were significantly larger than those demonstrating no invasion. However, no significant difference was found in the frequency of PCNA- or MIB1-positive cells between adenomas with and without cavernous sinus invasion.These findings suggest that cavernous sinus invasion and growth rate are independent biological factors. Therefore, cavernous sinus invasion may be due to chemical factors produced by the tumour itself rather than as a result of rapid tumour growth.

MIB1 immunopositivity is associated with rapid regrowth of pituitary adenomas

SummaryPituitary adenomas are generally regarded as benign tumours, but they may recur. We identified eight patients with pituitary adenomas that showed rapid regrowth within 2 years of initial surgery. We estimated the percentage of cells in each specimen that showed positive immunostaining for MIB1 (a novel anti-Ki-67) and compared the values to those of 40 adenomas that showed no regrowth. The mean MIB1 index for 40 adenomas that showed no evidence of regrowth was 0.19±0.06%. This was significantly (p<0.0001) lower than that for adenomas that showed rapid regrowth (1.27±0.31%), based on the initial resected specimens. Immediately after detection of rapid regrowth and in adenomas that were resistant to bromocriptine or irradiation, the MIB1 index was always greater than 1.0%. Most patients with rapidly regrowing adenomas were well controlled by radiation therapy.Our results suggest that a MIB1 index greater than 1.0% may be a useful predictor of rapid regrowth of pituitary adenomas and may be useful for planning of therapy.

Matrix metalloproteinase-9 secretion by human pituitary adenomas detected by cell immunoblot analysis

SummaryTwenty-two pituitary adenomas were examined on the secretion of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) using a cell immunoblot assay, and discussed regarding an association between cavernous sinus invasion and the secretion of these proteins. The cell immunoblot assay, a kind of immunoblot procedure, is able to detect proteins at the single cell level and to detect the incidence of tumour cells secreting the target proteins in the total tumour cell population. The incidence of tumour cells secreting MMP-9 was significantly higher in invasive adenomas than in noninvasive ones. On the other hand, TIMP-1 secretion was not detected in any adenomas in this study. This result suggested that MMP-9 secretion, and especially the number of MMP-9-secreting cells, may be associated with cavernous sinus invasion of pituitary adenomas.

Dissecting aneurysm of basilar artery presenting with recurrent subarachnoid hemorrhage.

Abstract Spontaneous basilar dissecting aneurysms secondary to subarachnoid hemorrhage are rare, usually presenting with ischemia rather than a subarachnoid hemorrhage (SAH). A 63-year-old man who had SAH repeatedly from a ruptured basilar dissecting aneurysm was treated with endovascular occlusion of the unilateral vertebral artery. Postoperative angiograms 1 month after the procedure showed complete obliteration of the aneurysm. The clinical follow-up at 20 months showed no evidence of recurrent hemorrhage.