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Biomedical subjects

Yasumasa Monden

Publications and source records attributed to Yasumasa Monden.

At least 19 recordsLinked to original sources

The reduced expression and aberrant methylation of p16(INK4a) in chromate workers with lung cancer.

STUDY OBJECTIVES: It is known that chromium is one of the important inhaled carcinogens that cause lung cancer. Our previous studies revealed a variety of genetic changes in lung cancers from chromate-exposed workers (chromate lung cancer). However, the epigenetic effects of chromium are not understood. MATERIALS AND METHODS: We investigated the methylation of the p16 gene using a methylation-specific PCR method in 30 chromate lung cancers and 38 non-chromate lung cancers, and the expression of the p16 protein using immunohistochemistry in 25 chromate lung cancers. RESULTS: Ten (33%) chromate lung cancers showed methylation of the p16 promoter region. On the other hand, 10 (26%) of the non-chromate lung cancers also showed it. The frequency of p16 methylation in non-chromate lung cancer was 0%, 33% and 30% for low (< or =600), moderate (<600, >1000) and high (> or =1000) Brinkman indexes, respectively. However, the frequency of p16 methylation in chromate lung cancer was constant, irrespective of the Brinkman index. In chromate lung cancer, patients with chromate exposure of less than 15 years never had p16 methylation, while 40% (> or =25 years) or 43% (> or =15, <25 years) of patients with chromate exposure of more than 15 years did. In chromate lung cancer, chromate exposure, not smoking, mainly influenced the p16 methylation. Most of the chromate lung cancers with p16 methylation (85.7%) showed repression of the p16 protein. CONCLUSIONS: We speculate that not only genetic but also epigenetic alterations are involved in the carcinogenesis due to chromium.

Adult↗

Microsatellite instability and protein expression of the DNA mismatch repair gene, hMLH1, of lung cancer in chromate-exposed workers.

Our previous studies of lung cancer in chromate-exposed workers (chromate lung cancer) have revealed that the frequency of replication error (RER) in chromate lung cancer is very high. We examined whether the RER phenotype of chromate lung cancer is due to an abnormality of DNA mismatch repair protein. We investigated the expression of a DNA mismatch repair gene, hMLH1, and hMSH2 proteins using immunohistochemistry and microsatellite instability (MSI) in 35 chromate lung cancers and 26 nonchromate lung cancers. Lung cancer without MSI or with MSI at one locus was defined as "RER(-)," lung cancer with MSI at two loci was defined as "RER(+)," and lung cancer with MSI at three or more loci was defined as "RER(++)." The repression rate of hMLH1 and hMSH2 proteins in chromate lung cancer was significantly more than that of nonchromate lung cancer (hMLH1: 56% vs. 20%, P = 0.006, hMSH2: 74% vs. 23%, P < 0.0001). In chromate lung cancer, the repression rate for hMLH1 was 43% in RER(-), 40% in RER(+), and 90% in the RER(++) group. The repression rate of hMLH1 protein in the RER(++) group was significantly higher than that in the RER(-) and RER(+) groups (P = 0.039). The inactivation of hMLH1 expression strongly correlated with the microsatellite high instability phenotype in chromate lung cancer. The genetic instability of chromate lung cancer is due to the repression of hMLH1 protein.

Adaptor Proteins, Signal Transducing↗

Thymoma and myasthenia gravis: a clinical study of 1,089 patients from Japan.

BACKGROUND: The thymus or thymoma plays a role in the pathogenesis of myasthenia gravis (MG). Although previous studies have reported that the presence of MG in thymoma patients is an indicator of poor prognosis, recent reports have shown that the presence of MG no longer influences the prognosis or indicates a more favorable prognosis in thymoma patients. METHODS: To clarify the difference in tumor behavior between thymoma with MG and that without MG, we compiled 1,089 thymomas treated between 1990 and 1994 from 115 institutes in Japan and analyzed the clinical characteristics of thymoma with MG compared with thymoma without MG. RESULTS: MG was associated with 270 cases (24.8%) of thymoma. The total resection cases comprised 94.6% and 91.4%, and the recurrent cases comprised 6.4% and 8.3% in the groups with and without MG, respectively. The 5-year survival rates for thymoma with and without MG in stage III were 85.7% and 89.3%, respectively; and those in stage IV were 85.1% and 63.9%, respectively. The prognosis of thymoma with MG in stage IV tended to be better than that of thymoma without MG (p = 0.0523). The thymoma with MG group had fewer stage IVb thymomas than did the thymoma without MG group (15% vs 34%). The resectability rate in the thymoma with MG group was higher than that in the thymoma without MG group (60% vs 38%). CONCLUSIONS: Thymoma with MG is equally or less malignant than that without MG. The infrequency of stage IVb thymomas and the high resectability rate had an influence on the favorable prognosis of stage IV thymoma with MG.

Academies and Institutes↗

Myasthenia gravis appearing after thymectomy for thymoma.

OBJECTIVE: A few thymoma patients without myasthenia gravis (MG) have been observed to develop MG after total removal of the thymoma (postoperative MG). However, the cause of this is not yet known because of the rarity of postoperative MG patients. This study evaluated the clinical characteristics of the 8 postoperative MG patients. METHODS: We compiled 1089 thymoma patients treated between 1990 and 1994 in 115 institutes in Japan, and found 8 cases of postoperative MG. RESULTS: Postoperative MG was found in 8 (0.97%) of 827 thymoma patients without preoperative MG. The postoperative MG patients included 1 male and 7 females, with a mean age of 50.5+/-15.0 years. The thymoma was completely resected in all cases. The surgical method used was extended thymectomy in 2 cases and thymothymectomy in 6 cases. There were 2 cases (0.7%) of postoperative MG in the extended thymectomy group (n = 275), 6 (1.9%) in the thymothymectomy group (n = 321), and none in the tumor resection group (n = 137). The interval between thymectomy and the onset of postoperative MG varied (6 days-45 months, 19.3+/-16.5 months). The type of MG was ocular in 2 cases and general in 5 cases, according to the modified Osserman classification. The postoperative MG was responsive to anti-cholinesterase compounds and/or steroids. The improvement rate was 86%. CONCLUSIONS: Postoperative MG was present in about 1% of the patients who underwent total thymoma resection. Resection of the thymus gland does not prevent postoperative MG.

Adult↗

Matrix metalloproteinase inhibitor MMI-166 inhibits lymphogenous metastasis in an orthotopically implanted model of lung cancer.

Matrix metalloproteinases (MMP) are considered to be critically involved in tumor invasion and the metastasis of various cancers. MMI-166 is a selective inhibitor of matrix metalloproteinase (MMP-2, MMP-9, and MMP-14). The purpose of this study was to evaluate the effects of MMI-166 on both the growth of the implanted tumor and the lymph node metastasis of the mediastinum and prolonging the life span, using an orthotopic implantation model of the Ma44-3 cancer cell line. We examined the anti-invasive effect of MMI-166 in lung cancer cell lines using an in vitro invasion assay. Next, we examined the anticancer effect of MMI-166 in vivo. MMI-166 (200 mg/kg body weight) or a vehicle was administered orally to the orthotopically implanted lung cancer model. MMI-166 dose-dependently inhibited the invasion of cancer cell lines with expressions of MMP-2 and/or MMP-9 in vitro. In vivo, MMI-166 significantly inhibited mediastinal lymph node metastasis in this orthotopic model (weight of the mediastinum: control, 0.089 +/- 0.009 versus MMI-166, 0.069 +/- 0.008 mg; P = 0.005; metastatic area: control, 93,495 +/- 55,747 versus MMI-166, 22,747 +/- 17,478 pixels; P = 0.045). MMI-166 prolonged the life span by 6 days in median survival time in the orthotopically implanted model (P = 0.039). These results showed that MMI-166 could possibly inhibit lymph node metastasis and prolong the life span in lung cancer patients.

Animals↗

Microscopic analysis of the chromium content in the chromium-induced malignant and premalignant bronchial lesions of the rat.

OBJECTIVE: Our previous studies demonstrated that the frequency of gene instability in lung cancer of chromate workers was very high, but the frequencies of the p53 and ras gene mutations were low. To clarify the carcinogenesis of chromate in the lung, we established a chromate-induced cancer model in the rat proximal airway and examined the relationship between chromium accumulations and the chromium-induced cancer and premalignant bronchial lesions of the rat. METHODS: Fifteen male, bred, 12-week-old Jcl-Wister rats were used. A pellet of strontium chromate were inserted into the bronchus of the rats. The rats were sacrificed 9 months after the pellet was inserted. We pathologically examined the region of the bronchi to which the pellet was attached. We quantified the amount of chromium accumulation in the bronchial lesions using a microscopic X-ray fluorescence analyzer. RESULTS: Of the 15 rats, 1 rat had a lesion of squamous cell carcinoma (SCC), 7 rats had carcinoma in situ (CIS) or dysplasia, 8 rats had squamous metaplasia, and 5 rats had goblet cell hyperplasia. The amounts of chromium accumulation in normal epithelium (n=24), goblet cell hyperplasia (n=14), squamous metaplasia (n=8), and dysplasia plus CIS plus SCC (n=9) were 500+/-1354, 713+/-1062, 941+/-1328, and 3511+/-4473 (mean+/-SD) counts/s/mA, respectively. The amount of chromium accumulation was significantly increased according to the progression of malignant change of the bronchial epithelium (Spearman's correlation coefficient by ranks, rs=0.454, P<0.01). CONCLUSIONS: The amount of chromium accumulation was significantly increased according to the progression of malignant change of the bronchial epithelium. Examining the genetic alterations of histologic changes in this model was helpful in elucidating the process of carcinogenesis of chromium in the lung.

Animals↗

WHO histologic classification is a prognostic indicator in thymoma.

BACKGROUND: The histologic classification of thymoma has remained a subject of controversy for many years. In 1999, the World Health Organization Consensus Committee published a histologic typing system for tumors of the thymus. METHODS: We reclassified a series of 100 thymomas resected at Tokushima University Hospital and four affiliated hospitals in Japan between 1973 and 2001 according to the World Health Organization histologic classification and reported its clinicopathologic relationship and prognostic relevance. RESULTS: There were 8 type A, 17 type AB, 27 type B1, 8 type B2, 12 type B3, and 28 type C thymomas. The frequency of invasion to neighboring organs increased according to tumor subtype in the order A (0%), AB (6%), B1 (19%), B2 (25%), B3 (42%), and C (89%). There was no recurrence in patients with type A, AB, or B2 thymoma. The recurrence rates of patients with B1, B3, or C thymoma were 15%, 36%, and 47%, respectively. The disease-free survival rates were 100% for types A and AB, 83% for types B1 and B2, 36% for type B3, and 28% for type C thymoma at 10 years. There were significant differences in disease-free survival between types A and AB and types B1 and B2 (p = 0.0436), and between type B3 and type C (p = 0.042). By multivariate analysis, only Masaoka clinical stage (p = 0.002) showed significant independent effects on disease-free survival. The 10-year survival rates of types A and AB, types B1 and B2, type B3, and type C thymoma were 100%, 94%, 92%, and 58%, respectively. CONCLUSIONS: The current study confirmed the World Health Organization histologic classification as a good prognostic factor.

Adolescent↗

Novel bronchofiberscopic catheter spray device allows effective anesthetic spray and sputum suctioning.

STUDY OBJECTIVES: To evaluate how serum lidocaine concentrations (SLC) rise when lidocaine is administered by a Bronchofiberscopic Catheter Spray Device (BCSD), and to demonstrate the effect on the aspiration speed of a substitute for sputum when a catheter spray remains in the channel of the bronchofiberscope (BF). METHODS: This is a prospective randomized clinical study. After lidocaine ultrasonic nebulizer, the BF was inserted orally. During the procedure patients received 4% lidocaine by two methods. In Group 1, 11 patients received lidocaine by bronchofiberscopic (BF) injection. In Group 2, 15 patients received lidocaine by spraying from the diameter 1.06 mm catheter through the BF channel. SLC were measured at 40 min from onset of nebulization. Separately, we examined how effectively sputum was aspirated through the BF channel with a catheter. RESULTS: Total lidocaine dose (TLD) is the total dose used for nebulization and for the BF injection or spray. The TLD for Groups 1 and 2 were 698.2+/-162.1 mg (mean+/-SD) and 498.7+/-103.8 mg, respectively (P = 0.03). The SLC for Groups 1 and 2 were 1.28+/-0.72 and 1.48+/-0.70 mg/l, respectively (P = 0.49). CONCLUSIONS: Using BCSD allows easier in administration of lidocaine and is not associated with a significant increase in SLC in comparison with BF injection. Although sputum aspiration using the BF inserted with our catheter was somewhat slow, we did not feel inconvenient so much. Compared to the conventional method, using BCSD may be preferable for patients and bronchoscopists.

Adult↗

Determination of tamoxifen--DNA adducts in leukocytes from breast cancer patients treated with tamoxifen.

Tamoxifen (TAM), a widely used antiestrogen for breast cancer therapy and chemoprevention, increases the incidence of endometrial cancer in women. The formation of DNA adducts induced by tamoxifen may initiate endometrial cancer. To evaluate the genotoxic risk of TAM, the formation of DNA adducts in leukocytes was examined. Blood samples were collected from 47 breast cancer patients (61.7 +/- 12.5 years) taking TAM (20 mg/day; average duration until sampling, approximately 37 months) and 20 untreated patients (58.2 +/- 12.3 years), and their leukocyte DNA was analyzed by 32P-postlabeling/HPLC analysis. This assay resolves synthetic standards, trans- and cis-diastereoisomers of alpha-(N2-deoxyguanosinyl)tamoxifen 3'-monophosphate (dG3'P-N2-TAM), alpha-(N2-deoxyguanosinyl)-N-desmethyltamoxifen 3'-monophosphate (dG3'P-N2-N-dMeTAM), and alpha-(N2-deoxyguanosinyl)tamoxifen N-oxide 3'-monophosphate', and is capable of determining TAM adducts quantitatively. The detection limit of this assay is 0.6 adducts/10(9) nucleotides. trans-dG3'P-N2-TAM (fr-2; one of the two trans-isomers) was detected in six of 47 breast cancer patients treated with TAM. Among them, trans-dG(3'P-N2-N-dMeTAM (fr-2) was also detected in two patients. The total amounts of TAM-DNA adducts in the positive patients were 2.6 +/- 3.0 adducts/10(9) nucleotides. No adducts were detected in the controls. The presence of TAM-DNA adducts in the leukocyte DNA samples was confirmed using several 32P-postlabeling/HPLC systems.

Aged↗

Orthotopically implanted SCID mouse model of human lung cancer suitable for investigating metastatic potential and anticancer drug effects.

To evaluate the effects of drugs in clinical settings, an animal model of lung cancer similar to clinical cancer is necessary. Our previous studies described an SCID mouse model using orthotopic implantation of the human lung cancer cell line which mimicked the lymph node metastasis of patients with lung cancer. In this study, we made animal models that reflected various metastatic forms of lung cancer in humans. We applied our procedure to 6 lung cancer cell lines. Suspensions of 2.0 x 10(4) cancer cells were injected into the left lung of SCID mice. We evaluated the mRNA expressions of 52 proteins related to the metabolism of and resistance to anticancer drugs of each tumor cell line and its orthotopically implanted tumor using a customized cDNA array. Three lung cancer cell lines had the potential of lymphogenous metastasis and 3 cell lines had the potential of hematogenous metastasis in this model system. The A549 line showed multiple metastases, and Ma2 line showed solitary metastasis. The expression of 52 genes in each implanted tumor was closely correlated with that in each cell lines (correlation coefficients: 0.8883-0.9533), and the gradient of the regression line was more than 0.9. This model was similar to the metastatic form in patients with lung cancer. The similar expression of proteins in each tumor cell line in vitro and implanted tumor in vivo gives an advantage in evaluating the effects of molecular-targeted drugs and the relationship between specific genes and tumor potential in preclinical studies.

Animals↗

Microscopic analysis of chromium accumulation in the bronchi and lung of chromate workers.

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.

Adult↗

Increased expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 is correlated with poor prognostic variables in patients with thymic epithelial tumors.

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.

Adult↗

Randomized controlled trial comparing oral doxifluridine plus oral cyclophosphamide with doxifluridine alone in women with node-positive breast cancer after primary surgery.

PURPOSE: We compared the therapeutic usefulness of doxifluridine (5'-DFUR) alone and a combination of 5'-DFUR plus cyclophosphamide (CPM), both of which are considered effective against advanced and recurrent breast cancer, to determine which treatment is more beneficial as postoperative adjuvant chemotherapy. PATIENTS AND METHODS: A total of 1,131 women with node-positive primary breast cancer were randomly assigned after primary surgery to receive 5'-DFUR alone or 5'-DFUR plus CPM. All patients initially received 5'-DFUR in an oral dose of 1,200 mg/d for 4 weeks, starting 4 weeks after surgery. Chemotherapy was then not given for 2 weeks. Patients in the 5'-DFUR group subsequently received five 4-week cycles of treatment consisting of oral 5'-DFUR (1,200 mg/d) for the first 2 weeks and no chemotherapy for the next 2 weeks. Those assigned to the 5'-DFUR plus CPM group also received oral CPM 100 mg/d for the first 2 weeks and no chemotherapy for the next 2 weeks. Women 50 years or older concurrently received 20 mg/d of tamoxifen for 2 years in both groups. RESULTS: Of the 1,088 eligible women, 546 were assigned to receive 5'-DFUR alone and 542 were assigned to receive 5'-DFUR plus CPM. Overall disease-free survival was significantly better in women who received 5'-DFUR plus CPM than in those who received 5'-DFUR alone (log-rank test, P =.021). Toxic effects occurred in 20.0% of patients (109 of 546) in the 5'-DFUR group and 32.3% of patients (175 of 542) in the 5'-DFUR plus CPM group (chi(2) test, P <.001). CONCLUSION: Combination therapy with 5'-DFUR plus CPM is more effective in preventing recurrence than 5'-DFUR alone.

Administration, Oral↗

Secretory carcinoma of the breast with a cystically dilated intraductal component: report of a case.

A case of secretory carcinoma of the breast in a 61-year-old woman is described. She came to our hospital complaining of a bloody nipple discharge. The physical examination revealed a 2.8 x 2.1-cm, firm, irregular lump with bloody nipple discharge in her left breast. Mammography demonstrated an irregular mass and ultrasonography showed an irregular hypoechoic mass accompanied with a cyst. Ductgraphy was done. It showed a dilated mammary duct leading to the cyst which was partially occupied with carcinoma. A cytologic smear of the nipple discharge and fine-needle aspiration cytology revealed similar findings, and both findings were malignant. A modified radical mastectomy was performed. A pathological examination revealed secretory carcinoma of the breast which had spread inward and outward from the cyst. In addition, the nipple discharge flowed from the cyst through the dilated mammary duct. The patient is presently alive and well 2 years after the operation. Secretory carcinoma is an extremely rare tumor of the breast and 48 cases have been reported in Japan. The present case is the first known case of secretory carcinoma demonstrating a bloody nipple discharge to come from a cyst which has been invaded by carcinoma.

Breast Neoplasms↗

Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan.

BACKGROUND: Surgery remains the mainstay of treatment for thymic epithelial tumors, and radiation and chemotherapy also have been applied widely as adjuvant and palliative procedures. METHODS: We compiled records of 1,320 patients with thymic epithelial tumors who were treated from 1990 to 1994 in 115 institutes certified as special institutes for general thoracic surgery by The Japanese Association for Chest Surgery. RESULTS: Patients with stage I thymoma were treated with only surgery, and patients with stage II and III thymoma and thymic carcinoid underwent surgery and additional radiotherapy. Patients with stage IV thymoma and thymic carcinoma were treated with radiation or chemotherapy. The Masaoka clinical stage is an excellent predictor of the prognosis of thymoma and thymic carcinoma, but not thymic carcinoid. In stage III and IV thymoma, the 5-year survival rates of total resection, subtotal resection, and inoperable groups were 93%, 64%, and 36%, respectively. On the other hand, in thymic carcinoma, the 5-year survival rates of total resection, subtotal resection, and inoperable groups were 67%, 30%, and 24%, respectively. Prophylactic mediastinal radiotherapy could not prevent local recurrences effectively in patients with totally resected stage II and III thymoma. Adjuvant therapy including radiation or chemotherapy did not improve the prognosis in patients with totally resected III and VI thymoma and thymic carcinoma. CONCLUSIONS: Total resection is the most important factor in the treatment of thymic epithelial tumors. There is value in debulking surgery in invasive thymoma, but not in thymic carcinoma. We doubt that adjuvant therapy is valuable for patients with totally resected invasive thymoma and thymic carcinoma.

Adolescent↗

Lymphogenous and hematogenous metastasis of thymic epithelial tumors.

BACKGROUND: A TNM classification has been established for various tumors. However, the TNM classification of thymic epithelial tumor has not been established yet. METHODS: We received replies to a questionnaire on thymic epithelial tumors from 115 institutes. We compiled a database of 1,320 patients with thymic epithelial tumor (1,093 thymomas, 186 thymic carcinomas, and 41 thymic carcinoids) who were treated between 1990 and 1994. We used a tentative TNM classification of thymoma presented by Yamakawa and associates in 1991. The regional lymph nodes of the thymus were classified into three groups: anterior mediastinal lymph nodes (N1), intrathoracic lymph nodes (N2), and extrathoracic lymph nodes (N3). RESULTS: The rate of lymphogenous metastasis in thymoma, thymic carcinoma, and thymic carcinoid was 1.8%, 27%, and 28%, respectively. Most tumors with lymph node metastasis metastasized to N1 (thymoma, 90%; thymic carcinoma, 69%; thymic carcinoid, 91%). The 5-year survival rates of N0, N1, and N2 thymoma were 96%, 62%, and 20%, respectively. The 5-year survival rates of N0, N1(,) N2, and N3 thymic carcinoma were 56%, 42%, 29%, and 19%, respectively. The 5-year survival rates of M0 and M1 thymoma were 95% and 57%. The 5-year survival rates of M0 and M1 thymic carcinoma were 51% and 35%. Multivariate analysis demonstrated that survival of patients with thymoma was dependent on the clinical stage of Masaoka and complete resection. In thymic carcinoma, survival was dependent on lymph node metastasis and complete resection. CONCLUSIONS: The N factor was one of the predictors of survival in thymoma and thymic carcinoma. However, M factor showed less influence on survival than T or N factors.

Carcinoid Tumor↗