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Background: It is known that chromium is an inhaled carcinogen and an important risk factor in the development of lung carcinoma., Methods: The authors used a microscopic X-ray fluorescence analyzer with transmitted X-ray mapping imaging (Horiba, Kyoto, Japan) to measure the accumulation of chromium in 10 resected lung tissue specimens and 90 biopsy specimens from chromate workers., Results: The maximum chromium accumulation (mean +/- standard deviation) in 10 resected lung tissue specimens was 197 +/- 238 counts per second (cps)/mili ampere (mA) (range, 4-649 cps/mA). Chromium accumulation was scattered in six tissue specimens and diffuse in one specimen. Chromium accumulation in the proximal bronchi was less than in the bronchioles or subpleural regions of the lung. Chromium accumulation was detectable in 63 (70%) of 90 biopsy specimens, and the mean accumulation was 6.5 +/- 9.2 cps/mA (range, 0-46.5 cps/mA). Chromium detected in bronchial tissue specimens was deposited in the bronchial stroma but not in the epithelium. The maximum chromium accumulations in dysplasic (n = 3), squamous metaplastic (n = 10), and normal bronchial epithelia (n = 9) in chromate workers and in normal bronchial epithelia (n = 3) in non-chromate workers were 20.2 +/- 5.4, 18.3 +/- 12.2, 13.2 +/- 13.4, and 3.0 +/- 1.8 cps/mA, respectively. The amount of chromium accumulation significantly increased according to the progression of malignant change of the bronchial epithelium (P = 0.003)., Conclusions: Previous studies found that lung carcinoma with chromate exposure exhibited a variety of genetic abnormalities. Considering genetic aberrations and chromium accumulation in these premalignant lesions is useful for elucidating the process of carcinogenesis in chromium-induced lung carcinoma., (Copyright 2003 American Cancer Society.)

Background: A distinction between noninvasive, invasive, and metastatic thymoma on the basis of the cytologic features is difficult. The current study investigated whether the expression of MMP and TIMP was correlated with tumor invasiveness and prognosis in patients with thymoma., Methods: Tumor tissue samples were obtained from 42 patients with thymic epithelial tumors between 1974 and 2001 at Tokushima University Hospital. Three-micrometer-thick, formalin-fixed, paraffin-embedded tissue sections were immunostained using specific antibodies against MMP-2, MMP-9, TIMP-1, and TIMP-2., Results: MMP-2 expression was detected in 30 tumors (71%), and TIMP-2 expression was detected in 31 tumors (74%). MMP-9 expression was detected in 22 of 36 tumors (61%), and TIMP-1 expression was detected in only 7 tumors (19%). MMP-2 and TIMP-2 expression levels were very low (10% and 0%, respectively) in noninvasive tumors but were very high (91% and 97%, respectively) in invasive tumors. In thymic epithelial tumors, the more progressive the clinical stage of tumor, the higher the strongly positive rate of MMP-2 and TIMP-2 expression. There was no correlation between positivity for MMP-9 and stage. Twenty-five percent of Type AB thymomas and 50% of Type B1 thymomas expressed MMP-2 and TIMP-2. Most of Type A, Type B2, Type B3, and Type C thymomas expressed MMP-2 and TIMP-2. There were significant differences in disease-free survival at 5 years between patients without and with MMP-2 expression (91% vs. 55%, respectively) and patients without and with TIMP-2 expression (100% vs. 53%, respectively)., Conclusions: MMP-2 and TIMP-2 are key enzymes for invasiveness of thymic epithelial tumors. The expression of these proteins can predict a poor outcome in patients with thymoma., (Copyright 2003 American Cancer Society.)

Background: It remains controversial whether modified radical neck dissection (MRND) for patients with papillary thyroid carcinoma improves prognosis. However, it is highly probable that the incidence of local recurrence is reduced by lymph node dissection. Sentinel lymph node (SLN) biopsy (SLNB) for patients with melanoma and breast carcinoma has been validated as an accurate method for assessing lymph node status. The objective of this study was to determine the feasibility of SLNB for the evaluation of cervical lymph node status in patients with papillary thyroid carcinoma., Methods: After injection of methylene blue around the tumor in 22 patients with papillary thyroid carcinoma, blue-stained lymph nodes were dissected as SLNs. After the SLNB, all patients also underwent subtotal thyroidectomy and MRND. SLNs and other lymph nodes were investigated with regard to their number, distribution, size, lymph node status, and ratio of metastatic area., Results: There was concordance between the SLN findings and the regional lymph node status in 19 of 21 patients (90.5%; 7 patients had both positive SLN and regional lymph node results, and 12 patients had both negative SLN and regional lymph node results). Two patients had negative SLN results but, in the end, had positive nonsentinel lymph nodes (NSLNs). The overall reliability rate of SLNB was 86.3% (19 of 22 patients). The authors experienced no complications with the use of methylene blue for the detection of SLNs., Conclusions: SLNB using methylene blue is feasible technically and is safe, and the findings correlate with cervical lymph node status. Therefore, SLNB is a good technique for estimating the status of cervical lymph nodes in patients with papillary thyroid carcinoma., (Copyright 2001 American Cancer Society.)

Background: Epidemiologic data suggested that the differentiated thyroid carcinoma was affected by sex hormones, especially estrogen., Methods: The authors have immunohistochemically studied estrogen receptors (ER) in papillary thyroid carcinoma in women. Two anti-ER monoclonal antibodies, D5 and H222, were used. The authors then investigated the responsiveness to estrogen of thyroid neoplasms using primary culture of surgically resected thyroid tissues. The proliferative activity of cultured cells was measured by the bromodeoxyuridine (BrdU) labeling index (LI)., Results: Twenty-six percent of the specimens (18/70) showed positive staining with D5, but only 5.6% of the specimens (2/36) showed positive staining with H222. The BrdU LI of ER-positive papillary thyroid carcinoma increased with the addition of estradiol., Conclusions: These findings indicate that estrogen may affect the proliferation of ER-positive papillary thyroid carcinoma.

Background: A randomized adjuvant trial was conducted from October 1982 to January 1985 to evaluate the addition of tamoxifen (TAM) to combination chemotherapy with perioperative mitomycin C (MMC) and ftorafur (FT) for patients with estrogen receptor (ER)-positive tumors and the addition of PSK, a biologic response modifier, to MMC+FT chemotherapy for patients with ER-negative tumors in operable Stage IIA, IIB, and IIIA cancer. The doses used were 20 mg of oral TAM daily, 600 mg of oral FT daily, and 3 g of oral PSK daily for 2 years. Intravenous MMC (13 mg/m2) was given on the day of operation., Methods: A total of 967 patients were entered and randomized by stratification based on ER status and staging (1978 International Union Against Cancer [UICC] criteria at the time of trial execution). Of 967 patients, 914 (94.5%) were evaluable. At 5-year follow-up, significant prolonged overall survival (OS) and relapse-free survival (RFS) times were seen with the addition of TAM in patients with ER-positive and Stage IIIA T3N0 cancer (1987 UICC-American Joint Committee on Cancer [AJCC] criteria); however, no significant survival benefit from TAM was seen in patients with ER-positive and Stage IIA T2N1 cancer. There was no significant difference between regimens, with or without PSK, in patients with ER-negative disease., Results: Results of subset analyses suggested a benefit from TAM in postmenopausal patients with ER-positive and Stage IIA T2N1 cancer and a benefit from PSK in patients with node-negative, ER-negative, and Stage IIA T2N1 cancer., Conclusions: The 5-year results of the current trial showed a survival advantage by the addition of TAM to chemotherapy in patients with ER-positive and Stage IIIA T3N0 cancer.

Estrogen receptors (ER) and epidermal growth factor receptors (EGFR) in the tumor cells of breast cancer tissues (primary tumors) and metastatic lymph nodes (involved nodes) were analyzed by immunocytochemical study in 19 patients; 12 were ER positive, and seven were ER negative. Microscopic study was used to determine the percentage of positive cells and the staining index. The percentage of EGFR-positive cells and the EGFR staining index were higher in the ER-negative primary tumors than ER-positive primary tumors. In ER-positive cases, both the number of ER-positive cells and ER content per cell was less in the involved nodes than in the primary tumors, whereas the number of EGFR-positive cells and EGFR content per cell was greater in affected nodes. On the other hand, in the ER-negative cases the number of EGFR-positive cells and EGFR content per cell remain almost unchanged between the primary tumors and involved nodes. The authors supposed a probability, in this study, that estrogen may exert inhibitory action on EGFR production through binding to ER.

The behavior of sex hormone receptors was studied in the cytosol of thyroid tissue samples in order to clarify the effects of sex hormones on diseases of the thyroid. Androgen receptor (AR), estrogen receptor (ER), and progesterone receptor (PgR) were assayed using the dextran-coated charcoal (DCC) method and analyzed by the method of Scatchard. Androgen receptor, ER, and PgR were negative in all of the cytosol prepared from normal thyroid tissues. However, the positive rates for the receptors in the neoplastic and nonneoplastic tissues were 22% for AR, 29% for ER, and 18% for PgR. Especially, the incidence of ER was significantly higher in neoplastic lesions than normal tissues. These data suggest that sex hormones, especially estrogen, may play a role in diseases of the thyroid.

Eighteen patients (10 women and 8 men), ranging in age from 37 to 80 years, with thyroid carcinoma infiltrating the trachea comprised this series. Eleven had primary and 7 had recurrent cases. Total laryngectomy was performed in 4 patients, and tracheal resection was carried out followed by end-to-end anastomosis in 13 patients. In one patient, reconstruction was done with Naville's artificial trachea after tracheal resection. Eleven patients were alive after 1 year and 8 months to 6 years and 7 months after the operation. This result was significantly better than that of a group of ten patients without resection of the infiltrated trachea (seven patients died within 6 months). Thus, combined resection of the upper airway improved the prognosis of advanced thyroid carcinoma with tracheal infiltration. Histologic examination of surgical specimens demonstrated well-differentiated carcinoma in seven patients, poorly differentiated carcinoma in seven patients, undifferentiated carcinoma in three patients, and squamous cell carcinoma in one patient. The result showed a higher frequency of poorly differentiated carcinoma than in the control group of 70 patients without tracheal infiltration.

In 261 surgically treated patients with myasthenia gravis (MG), 26 had an invasive thymoma and 49 had a noninvasive thymoma. Invasive thymoma was seen in 41% of thymomatous MG patients older than 40 years of age, and 28% in patients younger than 40 years of age. Of 19 patients who underwent total or subtotal thymothymomectomy accompanied by irradiation (4000 rad), 17 were still alive on an average 6.5 years after surgery. The deterioration of MG by the irradiation was observed in 7 of 20 irradiated cases. Thus, postoperative irradiation is effective but should be done with attention to the deterioration of MG. The prognosis of MG in patients with an invasive thymoma was poorer than that in patients with a noninvasive thymoma.

In order to quantify the lymphocyte to epithelial cell ratio (L/E ratio of the thymoma, actual counting was performed. The L/E ratio was investigated in 25 specimens of 22 cases (22 initial tumors and 3 recurrent tumors). L/E ratios ranged from 0.27 to 4.10, and the mean value was 1.93 +/- 0.21. The mean L/E ratio of histologically malignant group was lower than that of the benign group. In the three recurrent cases, L/E ratios of the recurrent tumor decreased in all cases. It was concluded that the epithelial element increases with the adva

Follow-up data were obtained for 96 cases of thymoma. The one-year survival rate was 84.3%, the three-year 77.1%, the five-year 74.1%, and the ten-year 57.1%. The five-year survival rate of total resection group was 88.9%; that of non-radically treated group was 44.4%. Clinical stages were defined: Stage I--macroscopically encapsulated and microscopically no capsular invasion; Stage II--1. macroscopic invasion into surrounding fatty tissue of mediastinal pleura, or 2. microscopic invasion into capsule; Stage III--macroscopic invasion into neighboring organ; Stage IVa--pleural or pericardial dissemination; Stage IVb--lymphogenous or hematogenous metastasis. Five-year survival rates of each clinical stage were 92.6% in Stage I, 85.7% in Stage II, 69.6% in Stage III, and 50% in Stage IV. Recurrence after total resection was found in six of 69 cases. Seven of 13 patients treated by subtotal resection survived more than five years with postoperative radiotherapy.

In 175 women with mucinous carcinoma (MC) of the breast, the morphologic features, the clinicopathological features (age, tumor size, and nodal status) and prognoses were investigated. They were divided into two types, those with "unmixed type" (n = 140) showing no component of invasive ductal carcinoma (IDC) and "mixed type" (n = 35) including an IDC component. The unmixed type showed less frequent (P less than 0.01) nodal involvement and a higher degree (P less than 0.005) of extracellular mucus production than the mixed type. The presence of nodal metastases showed no correlation with the degree of mucus production. The 10-year survival rate of the unmixed type (90.4%) was better (P less than 0.001) than in the mixed type (66.0%). In the unmixed type, a higher level of mucus production showed trends toward a better prognosis, younger age and smaller tumor size (P less than 0.01). In the mixed type, the degree of mucus production showed no significant correlation with either the age, tumor size, or prognosis. It is more important for the prognosis of patients with MC to have no IDC component than to show abundant mucus within the tumor.

A 35-year-old man was hospitalized with complaints of retrosternal pain and high fever. A chest radiograph showed a large round mass in the mediastinum. Of the several tumor markers in the serum tested, only CA 19-9 was elevated. Thoracotomy revealed a cystic mass with purulent hemorrhagic materials. Histologically the cyst was lined by bronchial epithelium with no evidence of malignancy. The high level of CA 19-9 in the cystic fluid, and positive immunohistochemical staining of the bronchial glands in the cyst wall for CA 19-9 indicated that the elevated serum level of CA 19-9 originated from the bronchogenic cyst after its infection.