Postpartum recurrence of hyperthyroidism and changes of thyroid-stimulating immunoglobulins in Graves' disease.

The changes of circulating thyroid-stimulating antibody (TSAb) in three patients with Graves' disease with relapsed hyperthyroidism after delivery were examined. All three patients were in clinical remission before and during pregnancy, but hyperthyroidism, with high radioactive iodine uptake, recurred 3--5 months post partum. TSAb activity, measured serially, was not detected at the time of the postpartum relapse, although it was detectable during pregnancy and in the euthyroid state after therapy. In two cases, the titer of antithyroid microsomal antibody increased concomitantly with an increase in the free T4 index. These data suggest that TSAb may not be a pathological thyroid stimulator in patients with recurrent hyperthyroidism after delivery in Graves' disease.

Elevated levels of circulating carcinoembryonic antigen in hypothyroidism.

The level of circulating carcinoembryonic antigen (CEA) was measured in 148 patients with various thyroid diseases. A significantly high frequency of positive CEA was observed in hypothyroid patients with Hashimoto's disease, but the serum CEA levels were not correlated with the serum calcitonin concentrations in Hashimoto's disease. The CEA levels were inversely correlated with the serum T4 concentrations (P less than 0.001) and were positively correlated with the serum TSH concentrations (P less than 0.001), but not with the titers of serum antithyroid antibodies or the size of goiter in autoimmune thyroid disease. Moreover, the increase in CEA was significantly related to the duration of hypothyroidism (P less than 0.001). The high CEA levels in all hypothyroid patients decreased when the patients attained a euthyroid state after thyroid hormone therapy for 4-9 months. The gradual decrease in the serum CEA levels during treatment was roughly correlated with the decreases in serum cholesterol concentration and serum lactic dehydrogenase and glutamic oxalacetic transaminase activities. On Sephadex G-200 column chromatography of serum from hypothyroid patients, the CEA immunoreactivity, like purified standard CEA, was recovered in the large molecular weight fraction. These findings indicate that elevated CEA levels in hypothyroid patients do not necessarily indicate malignancy. CEA elevation in hypothyroidism may be caused by decreased degradation of CEA.

The expression of urokinase type plasminogen activator is a novel prognostic factor in dukes B and C colorectal cancer.

Urokinase type plasminogen activator (u-PA) secreted by cancer cells is considered to play a key role in promoting invasion and metastasis of cancer cells. This study was designed to evaluate the expression and prognostic value of u-PA in Dukes B and C colorectal cancer. u-PA expression was investigated in 57 Dukes B or C colorectal cancers using a monoclonal antibody against u-PA. u-PA expression was mainly observed on the cytoplasm of cancer cells, and was associated with relapse, especially hematogenous metastasis (p=0.025, the chi2 test). Patients with high u-PA expression had a lower rate of DFS (9/22 events) compared to those with low u-PA expression (6/35 events) (p=0.061, log-rank test). This study demonstrated that u-PA expression might be a novel prognostic factor in Dukes B and C colorectal cancer.

Urokinase type plasminogen activator receptor is a novel prognostic factor in breast cancer.

BACKGROUND: There have been many reports that the u-PA system plays an important role in cancer invasion and metastasis. The binding of u-PA to its specific cell-surface receptor, u-PAR, is necessary for the activation of u-PA system. The aim of this study is to evaluate the role and the prognostic value of u-PAR in cancer invasion and metastasis. PATIENTS AND METHODS: u-PAR expression in 104 breast cancers was investigated immunohistochemically using a monoclonal antibody against u-PAR. RESULTS: u-PAR expression was mainly observed both on cancer cells and stromal cells. Patients with high u-PAR expression in cancer cells or stromal cells had a high relapse rate compared with patients with low u-PAR expression by the Kaplan-Meier method (p = 0.035 and 0.011, respectively). In uni- and multivariate analysis, u-PAR expression in stromal cells was significantly correlated with relapse (p = 0.017 and 0.043, respectively). CONCLUSIONS: This study has shown that not only cancer cells but also stromal cells have an important roles in breast cancer invasion and metastasis, and that u-PAR expression in cancer cells and stromal cells might be a novel prognostic factor in breast cancer.

Possible involvement of calpain in the growth of estrogen receptor positive breast cancer cells.

Calpain (Ca2(+)-activated neutral protease, EC 3.4.22.17) has been reported to hydrolyze the estrogen receptor (ER). However, there has been no report available regarding the role of calpain in the growth of breast cancer cells. To investigate the role of calpain in the growth of various breast cancer cell lines, we employed a synthetic peptide, calpeptin, which is a cell permeable specific inhibitor of calpain. Calpeptin inhibited the cell growth of ER positive breast cancer cells, such as MCF-7, T-47D, and ZR-75-1 in a dose dependent manner in the presence of E2. However, the growth of ER negative breast cancer cells, MDA-MB-231, was not inhibited by calpeptin. It is suggested that calpain plays an important role in the growth of ER positive breast cancer cells.

Medullary carcinoma of the thyroid. Giant cell type.

This report presents a rare histological variation of medullary (C-cell) carcinoma of the thyroid, referred to as giant cell type, which is similar to that found in anaplastic carcinoma of the thyroid, or choriocarcinoma. The giant cells in this case possessed specific immunofluorescence for calcitonin and secretory granules in the cytoplasm. The giant cells were tumor cells of medullary carcinoma and could be distinguished from anaplastic carcinoma of the thyroid by various histological characteristics, such as nuclear invagination, an intermingled pattern of giant cells with typical small solid cells, infrequency of mitosis, and the existence of amyloid stroma.

Internal fistula as a route of infection in acute suppurative thyroiditis.

Seven cases of acute suppurative thyroiditis are described. Six patients had a recurrent painful swelling of the left anterior neck and one was seen at her first episode of the disease. A barium meal revealed a fistula originating from the apex of the left pyriform sinus in all cases. The fistula, a remnant of the fourth pharyngeal pouch, thus seems to be a common route of infection in acute suppurative thyroiditis, allowing bacterial infection to begin in the perithyroidal space and spread to the thyroid gland. Complete extirpation of the fistula is required for a permanent cure.

Phyllodes tumor in epileptics: a report of two cases.

Phyllodes tumor is an uncommon breast neoplasm characterized by a proliferation of both stromal and epithelial elements. In 1989, two young patients with phyllodes tumors were referred to our surgical department because of the detection of breast lumps. Interestingly, both patients also had epilepsy and had been taking anticonvulsants. An analytical case control study revealed that no significant difference between the control group and phyllodes group was found for various categories. In addition, no anticonvulsant medication had been prescribed in either the control group or the phyllodes group except for these two cases. We herein report two cases of phyllodes tumors occurring in two young epileptic patients.

Comparison of FDG-PET with MIBI-SPECT in the detection of breast cancer and axillary lymph node metastasis.

PURPOSE: The purpose of this work was to compare [18F]2-deoxy-2-fluoro-D-glucose (FDG) PET and 99mTc-methoxyisobutylisonitrile (MIBI) SPECT in the detection of breast cancer and axillary lymph node metastasis in the same patients. METHOD: FDG-PET and MIBI-SPECT were performed within 3 days for 40 women (age range 25-86 years old) with suspected breast cancer, in whom biopsies and/or mastectomies were performed. Both images were visually assessed, and the count ratio between tumor and normal tissue (T/N ratio) was calculated. RESULTS: Thirty-eight patients had breast cancer, and the remaining two had benign breast lesions. The sensitivities of FDG-PET and MIBI-SPECT were 78.9 and 76.3% for breast cancer and 50.0 and 37.5% for axillary lymph node metastasis, respectively. The T/N ratio of breast cancer was significantly higher in FDG-PET (6.01 +/- 3.08 mean +/- SD) than that in MIBI-SPECT (3.48 +/- 1.21) (p = 0.01). Nonmalignant diffuse uptake of FDG in the breasts and the accumulation of MIBI in heart and liver occasionally obscured tumor uptake. CONCLUSION: These results indicate that MIBI-SPECT is comparable with FDG-PET in detecting breast cancer. Neither FDG-PET nor MIBI-SPECT is sufficiently sensitive to rule out axillary lymph node metastasis.

Genotype-phenotype correlation in multiple endocrine neoplasia type 2: report of the International RET Mutation Consortium.

The International RET Mutation Consortium was first convened as part of the Fifth International Workshop on Multiple Endocrine Neoplasia, Stockholm, Sweden, in an attempt to analyse the relationship of RET mutation and disease phenotype in the autosomal dominantly inherited multiple endocrine neoplasia type 2 (MEN 2) syndromes. Out of 361 families studied, 41% had MEN 2A, 17.7% MEN 2B, 6.4% FMTC and the remaining subjects were unclassified. RET mutations were detected in 87.3% of families overall. Over 93% of MEN 2B families had the RET 918 ATG-->ACG mutation, while the most frequent mutation detected in MEN 2A families was cysteine codon 634 (87% of all mutations).

The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis.

OBJECTIVE: Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant disorder. The 3 recognized subtypes include MEN 2A, characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (pheo), and hyperparathyroidism (HPT); MEN 2B, by MTC, pheo, and characteristic stigmata; and familial MTC (FMTC), by the presence of MTC only. The purpose of this study was to establish the relationship between specific mutations and the presence of certain disease features in MEN 2 which could help in clinical decision making. DESIGN: Correlative survey study of 477 MEN 2 families. SETTING: Eighteen tertiary referral centers worldwide. PATIENTS: A total of 477 independent MEN 2 families. MAIN OUTCOME MEASURES: Association between the position and type of germline mutation in the RET proto-oncogene and the presence or absence of MTC, pheo, HPT, and/or other features in a family. RESULTS: There is a statistically significant association between the presence of any mutation at a specific position (codon 634) and the presence of pheo and HPT. The presence of a specific mutation, CGC at codon 634, has yet to be associated with FMTC. Conversely, mutations at codons 768 and 804 are thus far seen only with FMTC, while codon 918 mutation is MEN 2B--specific. Rare families with both MEN 2 and Hirschsprung disease were found to have MEN 2-specific codon mutations. Patients with Hirschsprung disease presenting with such mutations should be monitored for the possible development of MEN 2 tumors. CONCLUSIONS: This consortium analysis suggests that genotype-phenotype correlations do exist and, if made reliably absolute, could prove useful in the future in clinical management with respect to screening, surveillance, and prophylaxis, as well as provide insight into the genetic effects of particular mutations.