Clinical recurrence of papillary thyroid cancer in the remnant lobe.

OBJECTIVE: To find out which factors predict recurrence of cancer in the remnant after unilateral thyroid lobectomy for patients with papillary cancer. DESIGN: Retrospective study. SETTING: Teaching hospital, Japan. SUBJECTS: One hundred thirty-three patients with a clinically solitary papillary thyroid cancer who had unilateral lobectomy for the primary disease between 1966 and 1990 and were followed up for more than 60 months. Twelve patients had developed recurrences in the remnant gland by the time of the second operation and 121 patients had not as judged by a second operation, an ultrasound examination, or by palpation. RESULT: The primary tumour size in those who developed recurrences was significantly larger than in those who did not (p < 0.0001), and clinical signs of regional lymph node involvement or distant metastases were also significantly more common (p = 0.006). No patient died of their cancer. CONCLUSION: Size of the primary tumour is an important prognostic factor for recurrence of solitary papillary thyroid cancer in the remnant after unilateral lobectomy. Such recurrences are unlikely to be lethal.

Pure clear cell papillary thyroid carcinoma with chronic thyroiditis: report of a case.

We herein report a case of pure clear cell papillary thyroid carcinoma, which is the first reported case in Japan. The tumors measured 1.0 x 0.9 and 0.7 x 0.4 cm in size. An ultrasonographical examination revealed hypoechoic irregular-shaped lesions with fine internal calcifications. No lymph node metastasis was observed in any of the surgical specimens. Distant metastasis had not been observed as of 6 years after surgical treatment. The number of cases of pure clear cell papillary carcinoma reported so far are too few to clearly elucidate its characteristics; however, the ultrasonographical findings and biological behavior of this case were compatible with those of non-clear cell papillary thyroid carcinoma.

The relationship between multiple intrathyroidal involvement in papillary thyroid carcinoma and chronic non-specific thyroiditis.

The relationship between multiple intrathyroidal involvement (MII) and chronic non-specific thyroiditis (CT) was investigated in 69 papillary thyroid carcinoma patients who received a subtotal or total thyroidectomy. The overall incidence of MII in patients with CT and the incidence of MII in the affected lobe of the patients with CT were significantly higher than that without CT (P = 0.0012 and 0.0425, respectively). Because Hashimoto's thyroiditis is believed not to carry the increased risk of associated thyroid malignancy, the high incidence of MII in the affected lobe in the case with CT is postulated to be caused by intraglandular metastases.

Therapeutic efficacy of the angiogenesis inhibitor O-(chloroacetyl-carbamoyl) fumagillol (TNP-470; AGM-1470) for human anaplastic thyroid carcinoma in nude mice.

TNP-470 (AGM-1470), a synthetic analog of fumagillin (6-chloroacetyl-carbamoyloxy-4-(1,2-epoxy-1,5-dimethyl- 4-hexenyl)-5-methoxy-1-oxaspiro [2,5] octane 1, has been reported to reduce the supply of nutrients to experimental tumors by inhibiting angiogenesis. In this study, we investigated anti-tumor activity of TNP-470 against human thyroid anaplastic carcinoma with a view to developing a new treatment for this thyroid tumor. A transplantable tumor was established from thyroid anaplastic carcinoma of a 78-year-old woman, as a xenograft in nude mice (BALB/c, nu/nu, male). This transplantable tumor, with chromosomal abnormality was shown to be non-functional in excretory hormones and to preserve morphological characteristics of the original anaplastic tumor tissue. TNP-470 was given at a dose of 50 mg/kg b.w. to nude mice transplanted with human thyroid anaplastic carcinoma by different routes of administration: intratumoral, peritumoral, subcutaneous and intraperitoneal. Intratumoral and peritumoral administration were effective, and especially the TNP-470 administered by the former route completely inhibited tumor growth. Immunohistochemical analysis using anti-factor VIII antibody revealed the density of microvessels to be significantly decreased by local administration of TNP-470 (intratumoral administration, 7.8 +/- 2.9/mm2, control, 27.0 +/- 6.3/mm2; peritumoral administration, 9.7 +/- 2.6/mm2, control, 21.1 +/- 5.1/mm2). Our findings suggested the possibility of clinical application of TNP-470 to control the growth of human anaplastic thyroid carcinoma.

Adverse effects of intraportal chemotherapy on natural killer cell activity in colorectal cancer patients.

BACKGROUND: Adjuvant intraportal chemotherapy has been used with a view to prevent the development of metachronous hepatic metastases following curative resection for colorectal cancer. To evaluate the effects of this therapy on systemic antitumor immunological activity, 35 colorectal cancer patients who underwent curative resection were investigated. METHOD: Among them. 19 had adjuvant intraportal chemotherapy with mitomycin C and 5-fluorouracil (treated group) and 16 had no chemotherapy (untreated group). Natural killer (NK) cell activity, lymphocyte subpopulations, and immunosuppressive acidic protein (IAP) in the peripheral blood were measured serially before and after operation, and the values were compared between the two groups. RESULTS: The NK cell activity and the percentages of CD16 positive and CD56 positive cells were markedly reduced in the treated group postoperatively. Significant difference was also observed between the two groups on the 4th postoperative day in regard to NK cell activity and CD56 positive cells. CONCLUSIONS: Intraportal chemotherapy in our study reduced the NK cell activity and its population in the peripheral blood.

Postoperative outcome of insufficient surgery for small differentiated thyroid carcinoma.

We performed conservative surgery for small differentiated thyroid carcinoma, but also inadvertently carried out minimal insufficient surgery, such as enucleation (Ex) or partial lobectomy (pLx) without regional node dissection for malignant thyroid nodules. In this study, the long-term postoperative outcome after such insufficient surgical treatment was evaluated. Of 348 patients with differentiated thyroid carcinoma who underwent initial surgery between 1953 and 1976, 84 underwent either Ex or pLx and their records are herein reviewed. The frequency of recurrence from the remnant gland or regional lymph nodes was examined in relation to the tumor diameter (< or = 1.0 cm, tis; 1.0 cm-2.0 cm, t1; > 2.0 cm, t2). After Ex/pLx, the recurrence rate in the tis group was 13.3% and not significantly different from that (13.6%) in the t1 group. The recurrence rate was notably increased in the t2 group. Moreover, there was no significant difference between the recurrence rate in the tis and t1 groups after Ex/pLx and that after lobectomy with nodal dissection. These results suggest that a reoperative procedure with a more extensive thyroidectomy and neck dissection might not necessarily be required immediately after minimal insufficient surgery is inadvertently carried out in patients with small differentiated thyroid carcinoma measuring 2.0 cm in diameter or less.

Squamous cell carcinoma arising from thyroglossal duct remnants: report of a case and results of immunohistochemical studies.

We report on the case of a 57-year-old male found to have squamous cell carcinoma (SCC) arising from thyroglossal duct remnants. The patient presented with an asymptomatic tumor in his anterior neck which was immovable on palpation. Aspiration biopsy cytology revealed class V malignancy with many atypical clusters and marked keratinization. After preoperative radiation, a radical operation employing Sistrunk's procedure with bilateral neck dissection was performed. Histopathological examination confirmed a diagnosis of moderately differentiated SCC, but revealed ciliated columnar epithelium in the walls of the cyst without a normal layer of squamous cells. Furthermore, immunohistochemical studies demonstrated the tumor to be negative for thyroglobulin staining, but positive for cytokeratin and carcinoembryonic antigen. These histopathological findings proved attributable to squamous metaplasia occurring in the ciliated columnar epithelium of the thyroglossal duct. Thus, SCC might originate in the metaplastic portion of the thyroglossal duct remnants. Although the prognosis associated with SCC in the thyroglossal duct is not as optimistic as that associated with papillary carcinoma, no evidence of recurrence has been observed in this patient in the 7 years since his operation. This suggests the effectiveness of our therapeutic approach for this unusual disease.

Assessment of proliferative activity of glandular cells in hyperfunctioning parathyroid gland using flow cytometric and immunohistochemical methods.

The proliferative activity of epithelial cells in hyperfunctioning parathyroid glands was estimated by flow cytometric and immunohistochemical procedures. A total of 30 parathyroid glands, 29 hyperfunctioning glands, and 1 normal gland were studied. The pathology of the 29 glands was determined to be hyperplasia in 19 and adenoma in 10. The S-phase cell population was expressed in terms of the S-phase fraction (%SPF) calculated from the histogram by DNA flow cytometry and in terms of the BrdU immunostaining labeling index (BrdU LI). Cells in all stages of the cell cycle were studied by Ki-67 immunostaining and expressed in terms of the labeling index (Ki-67 LI). Both BrdU LI and Ki-67 LI values were low, ranging from 0% to 0.58% and from 0.21% to 2.62%, respectively. The BrdU LIs were lower than the Ki-67 LIs, ranging from one-sixth to one-twelfth of the values depending on the disease. There were significant correlations between the two indices (p < 0.001). The %SPF determined by flow cytometry was consistently higher than both the BrdU LI and the Ki-67 LI. This discrepancy cannot be explained precisely, and further improvements are required for the flow cytometric analysis of %SPF. The cell cycle study by BrdU and Ki-67 immunohistochemistry suggested that the glandular cells of the hyperfunctioning parathyroid were characterized by low proliferative activity. No evidence of rapid cell turnover rate assumed from the flow cytometric study could be observed in the hyperfunctioning parathyroid gland.

Management of tracheal wall resection for thyroid carcinoma by tracheocutaneous fenestration and delayed closure using auricular cartilage.

BACKGROUND: In the case of advanced thyroid carcinoma invading the trachea, surgical procedures for tracheal resection are selected in relation to the degree of invasion. We created a tracheocutaneous fenestration that was later closed with a free auricular cartilage autograft. We present a simple and effective method for permanent closure of tracheostoma. METHODS: The surgical procedure for delayed closure consists of three steps: (1) preparing the hinge flap with additional undermining of the subcutaneous layer and the strap muscles; (2) removing a portion of the conchal cartilage from the auricle, which is easily performed with a semicircular skin incision along the anthelix of the ear; and (3) placing the conchal cartilage with its convex surface upward just over the sutured hinge flap layer. RESULTS: Under local anesthesia, we successfully employed this reconstructive procedure for 5 patients. Unfortunately, however, in one patient, we had to reopen the closed tracheocutaneous fenestration on the second postoperative day because of an acute problem that was independent of the closure surgery. Four patients remain in satisfactory condition for more than 2 years since the closure of tracheostoma. CONCLUSIONS: The auricular cartilage free graft is a relatively simple procedure which supplies tracheal wall skeletal support for the permanent closure of the tracheocutaneous fenestration.

Frequent natural killer cell abnormality in children in an area highly contaminated by the Chernobyl accident.

Since January 1991, we have been performing thyroid surveys and hematologic and immunologic screening on children in Chechersk, Belarus, a city situated in one of the areas most seriously contaminated with high levels of radionuclides after the Chernobyl accident. Ten children selected from 713 children because of goiter did not show a decrease in humoral immunity or in the number and function of T cells. By contrast, natural killer (NK) cell activity against K562 cells was depressed in 4 of these 10 children. The clinical and laboratory findings indicated that previously reported diseases with NK cell dysfunction could be excluded. A comparative analysis of NK cell activity in children from areas with and without high 137Cs levels revealed a high frequency of abnormal NK cell activity only in children from the area contaminated by radioactive fallout. In addition, there was no correlation between NK cell activity and NK cell number as percentage in the children from the area with high 137Cs levels. Neither activity nor number of NK cells was correlated with the body content of 137Cs. Thus, the frequent abnormality of NK cell function may not have been due to actual internal exposure to the long-lived radionuclide.

Histopathological features of atrophic thyroiditis with blocking type-TSH binding inhibitor immunoglobulins.

To investigate the histopathological features of atrophic thyroiditis (AT) with blocking type-TSH binding inhibitor immunoglobulins (TBII), the present morphological observations were carried out employing additional immunohistochemical procedures. Moreover, these were compared with examples of goitrous Hashimoto's thyroiditis showing negative TBII (HT). There exist apparent differences between AT and HT. In particular, significant follicular atrophy with epithelial flattening including decreased positive staining of the follicular epithelial cells for thyroglobulin in AT was characteristically observed. These results suggest that the mechanism for the development of hypothyroidism in AT with blocking type-TBII might be due to suppression of thyroid cell function through the inhibition of endogenous TSH stimulation by the blocking antibody with subsequent epithelial degenerative destruction.

Expression of tissue-type plasminogen activator and its inhibitor couples with development of capillary network by human microvascular endothelial cells on Matrigel.

Human omental microvascular endothelial (HOME) cells seeded on Matrigel begin to migrate within 1 h, forming honeycomb-like structures and capillary-like networks within 18 h. Cross-sections of the capillary networks show them to be tube-like structures. Northern blot analysis showed that tissue-type plasminogen activator (t-PA) mRNA synthesis increased from the initial state at 0 h after seeding on Matrigel, reaching a steady state after 4 h. This elevated cellular t-PA mRNA level decreased markedly at 24 h. In contrast, the cellular plasminogen activator inhibitor-1 (PAI-1) mRNA level demonstrated biphasic curves during the 24 h after seeding on Matrigel: the PAI-1 mRNA level was increased eightfold initially at 4 h over that at 0 h, then declined, and again secondarily increased to greater than tenfold at 18 h. Cellular levels of both 72 kD type IV collagenase and tissue inhibitor of metalloproteinase (TIMP-2) mRNA were increased only a slightly within 2-4 h. These elevated mRNA levels were maintained for 18 h, while the TIMP-1 mRNA level increased up to 18 h, reaching around three times the level at 0 h. However, on collagen-coated dishes, cellular levels of t-PA, PAI-1, 72 kD type IV collagenase, TIMP-1, and TIMP-2 mRNA were not greatly changed during incubation for 24 h. On Matrigel, the cellular t-PA mRNA level at 18 h after seeding was greatly increased when treated with specific anti-transforming growth factor-beta (TGF-beta) antibody. In contrast, both PAI-1 and TIMP-1 mRNA levels at 18 h were reduced in the presence of anti-TGF-beta antibody. Development of the capillary network on Matrigel was inhibited in the presence of anti-t-PA antibody. Epidermal growth factor (EGF) enhanced t-PA gene expression and TGF-beta inhibited its expression in HOME cells cultured on collagen-coated dishes. On the other hand, TGF-beta enhanced cellular expression of the PAI-1 gene. The formation of a capillary network by HOME cells on Matrigel appears to be balanced by angiogenic EGF and anti-angiogenic TGF-beta through modulation of PA activity.

Thyroid abnormalities among children in the contaminated area related to the Chernobyl accident.

Gradual increases of various radiation-related diseases including thyroid cancer following the Chernobyl accident have been recently reported. We have carried out systematic thyroid surveys in school children aged 10-15 years in the highly contaminated area and compared the results with a similar survey in a nonaffected neighboring area as a control. Systematic examinations of the thyroid gland were performed in 888 schoolchildren (408 males and 480 females) in the districts of Chechelsk city with 5 to over 40 Ci/km2 of radiation level for 137Cs. In the control area (Bobruisk city), 521 children with the same age range (229 males and 292 females) were examined. Thyroid surveys were carried out as follows: palpation, ultrasonography, blood examinations of thyroid function, and measurements of daily urinary excretion of iodine. Certain thyroid abnormalities were observed in the high radioactive fallout area more frequently than in the control region. In particular, the prevalence of multiple micronodular lesions in diffuse goiter in the contaminated area was significantly higher than in the control area. However, endemic goiter due to iodine deficiency was present in both districts. The environment factor of iodine deficiency might have resulted in the early occurrence of ultrasonographic thyroid abnormalities attributed to radioactive contamination.

The safe and complete removal of a carotid body tumor with elements suggestive of a malignant potential by employing an intraluminal shunt: report of a case.

The carotid body tumor is a relatively rare neoplasm arising from the intercarotid paraganglions. We report herein the case of a patient with a Shamblin group 2 type carotid body tumor for which safe and successful removal was facilitated by the insertion of an intraluminal shunt. The patient was a 54-year-old man who presented with a spherical elastic mass, 4.8 x 3.7 cm in size, on the right anterior aspect of his neck, which was diagnosed as a carotid body tumor by diagnostic imaging. Because the tumor was suspected to be malignant based on the operative findings, which included invasive adhesion to the carotid artery, an intraluminal shunt was inserted, allowing for safe and complete removal. Histologically, this tumor showed malignant potential with sporadic mitoses and incomplete capsular invasion. Thus, it is recommended that an intraluminal shunt be employed for the removal of a carotid body tumor when it is found to be tightly adherent to the carotid artery during the operation.

Lower esophageal sphincter pressure after subtotal gastrectomy and postoperative reflux esophagitis.

Although reflux esophagitis after subtotal gastrectomy has been noticed by surgeons, the mechanism of its development is obscure. This study was undertaken with the aim of clarifying the role of the lower esophageal sphincter in the development of this abnormality. Manometric studies were carried out on 42 patients with gastric cancer, and on 19 with cholelithiasis. The lower esophageal sphincter pressure was measured using a catheter tip pressure transducer and a rapid pull-through technique, and the results presented as the mean of three measurements. The technical error of this experiment was estimated to be within 2 mmHg by a study of the cholecystectomy patients. After gastrectomy, the lower esophageal pressure decreased in 17 patients, increased in 4 and remained unchanged in 21. A more pronounced decrease in the lower esophageal sphincter pressure was found after Billroth II. Clinical evaluation of the 42 patients revealed symptoms of postgastrectomy regurgitation in 10. Preoperatively, these 10 had lower values of the lower esophageal sphincter pressure followed by a more marked postoperative decrease, as compared with the patients with no regurgitation symptoms. Oral administration of a test meal revealed regurgitation after subtotal gastrectomy. This study suggests that a low value of the pre-operative lower esophageal sphincter pressure, a marked decrease in the pressure after gastrectomy, and Billroth II anastomosis, may be factors that predispose to regurgitation.

[Combination neoadjuvant therapy with continuous intra-arterial CDDP infusion and radiotherapy for locally advanced breast cancer].

Neoadjuvant therapy combined with intra-arterial continuous infusion of CDDP and external radiation was evaluated in a patient with locally advanced breast cancer. Although only MR was observed on the primary tumor, PR was found in several metastatic lymph nodes and daughter nodules. All tumor markers elevated before treatment decreased to normal ranges only by this therapy, and histological damage was also recognized remarkably with a high concentration of free Pt (8.89 micrograms/g) in cancer tissues. Since no severe side effects appeared during the present therapy, extended radical mastectomy with wide skin resection could be performed following additional intra-arterial chemotherapy using 5-FU, epi-ADM and MMC. From this experience, it was suggested that CDDP was an useful drug in the chemotherapy for breast cancer.

Accentuated temporal line on the frontal skull radiograph: a sign of hyperparathyroidism.

PURPOSE: To determine the importance of a temporal line (the marginal line for the attachment of the temporal muscle to the skull) that is accentuated on frontal skull radiographs of hyperparathyroid patients owing to subligamentous bone resorption under the temporal muscle. MATERIALS AND METHODS: Radiographs from skeletal surveys of 134 surgically treated patients with primary (n = 102) or secondary (n = 32) hyperparathyroidism (HPT) and frontal skull radiographs of 63 age-matched control patients were reviewed. RESULTS: An accentuated temporal line was the most frequent finding (29.4% of cases) in primary HPT, followed by subperiosteal bone resorption in the hand (8.6%), salt-and-pepper appearance of the skull (3.5%), and rugger-jersey spine (1.1%). In secondary HPT, an accentuated temporal line became less obvious as subperiosteal bone resorption advanced. This finding was not seen in the control group. CONCLUSION: An accentuated temporal line is another radiographic indication of bone resorption in HPT.

Expression of basic fibroblast growth factor in thyroid disorders.

Morphologic and biologic studies were undertaken to clarify the biologic significance of basic fibroblast growth factor (bFGF) in human thyroid neoplasms. A total of 71 malignant tumors (50 papillary carcinomas, 14 follicular carcinomas, 7 anaplastic carcinomas), 11 follicular adenomas, 6 adenomatous goiters, and 6 Graves' disease tissues were examined employing immunohistochemical methods (avidin-biotin-peroxidase complex technique). An affinity-purified polyclonal rabbit antiserum to human bFGF was used as a primary antibody. The eluate of malignant thyroid tumor tissues from the heparin-Sepharose column was examined by Western blot analysis to elucidate the molecular weight form. With immunohistochemical staining, bFGF was frequently detected in the cytoplasm of malignant thyroid tumors compared to tissues of the benign diseases and normal controls. With anaplastic carcinoma, immunoreactivity of the tumor cells was particularly strong. In the correlative analyses between UICC TNM classification and bFGF staining in papillary carcinoma, there were significant differences when relating positive staining to the grade of nodal metastases. By Western blot analysis, the bFGF immunoreactivity was specifically detected in the two forms, with molecular weights of 18 and 33 kDa. The high-molecular-weight form was detected in only anaplastic carcinoma. The present investigations demonstrated a close correlation between the expression of bFGF and the degree of malignancy. bFGF might play an important role in promoting lymph node metastases. Moreover, the high-molecular-weight form of bFGF might have an intense influence on tumor growth.

Significance of values of thyrotropin binding inhibitor immunoglobulins and appearance of intrathyroidal lymphocytes at subtotal thyroidectomy for Graves' disease.

This study was undertaken to investigate whether thyrotropin binding inhibitor immunoglobulins (TBII) values at and after subtotal thyroidectomy correlated with the outcome or the histologic grade applied to the appearance of intrathyroidal lymphocytes at the time of surgical treatment. In addition, the main reason for the study was to determine whether or not it was possible to predict the outcome after the operation by the data obtained. There was no relation between the TBII results and the grade of the appearance of intrathyroidal lymphocytes at the time of operation or the TBII postoperative results (whether positive or negative) and the final outcome. However, it was of interest that patients with a recurrence of hyperthyroidism had the TBII values of more than 50 percent at the time of surgical treatment, and also manifested continuously positive TBII values after the operation. They also had moderate grades of lymphocytic infiltration and lymph follicle formation in the surgical specimen. It seemed impossible to predict the outcome of each instance in accordance with TBII values and the grade of the appearance of intrathyroidal lymphocytes at the time of the operation. However, it might be possible to predict at least the recurrence of hyperthyroidism by the consideration of changes of TBII values postoperatively.

Association of HLA-DPB1*0501 with early-onset Graves' disease in Japanese.

To investigate the association between HLA antigens and Graves' disease among Japanese, serologic typing and DPB1 genotyping using the PCR-RFLP method have been performed. HLA alleles of 106 patients with Graves' disease were determined, and the frequency of HLA-B46 was found to be significantly increased. Furthermore, the frequencies of HLA antigens were compared between two age groups: early-onset and late-onset patients (under and over 20 years, respectively). It was found that the frequency of DPB1*0501 (88.9%) was significantly increased (pc < 0.004) in the early-onset group as compared with the healthy controls (55.0%) but not in the late-onset group (60.7%). On the other hand, a significant increase of HLA-B46 was observed in the late-onset patients (pc < 0.0004). These results suggest that the genetic background of Japanese patients with early-onset Graves' disease is different from late-onset patients. Namely, the HLA-DP allele (DPB1*0501) and the HLA-B allele (B46) are primarily involved in the pathogenesis of early-onset and late-onset Graves' disease in Japanese, respectively.