Akira Masaoka

Follow-up study of thymomas with special reference to their clinical stages.

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 or 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 postopertive radiotherapy.

Extended thymectomy for myasthenia gravis patients: a 20-year review.

BACKGROUND Since 1973 we have performed extended thymectomy for myasthenia gravis because of the presence of thymic tissue in the anterior mediastinal fatty tissue. Follow-up results were reviewed and influencing factors were investigated. METHODS Three hundred seventy-five patients with myasthenia gravis (286 nonthymomatous and 89 thymomatous) who have undergone extended thymectomies were reviewed. The status of the patients was evaluated as follows: A (remission), B (improvement), C (no change), D (deterioration), E (death due to myasthenia gravis). Evaluation was performed at 3 and 6 months, and at 1, 3, 5, 10, 15, and 20 years. The effectiveness of the operation was estimated by the remission rate (RR = A/Total number of patients evaluated) and the palliation rate (PR = A + B/Total number of patients evaluated) at each point. RESULTS Remission rates of the nonthymomatous patients were 15.2% (3 months), 15.9% (6 months), 22.4% (1 year), 36.9% (3 years), 45.8% (5 years), 55.7% (10 years), 67.2% (15 years), and 50.0% (20 years). Remission rates in the thymomatous patients were 13.6% (3 months), 17.5% (6 months), 27.5% (1 year), 32.4% (3 years), 23.0% (5 years), 30.0% (10 years), 31.8% (15 years), and 37.5% (20 years). Absence of thymoma, younger age, and short duration of the disease were favorable prognostic factors. Thymectomy was effective also in patients with ocular myasthenia gravis. Preoperative steroid administration did not improve the outcome. CONCLUSIONS Extended thymectomy is an excellent operative procedure for myasthenia gravis in both nonthymomatous and thymomatous patients.

Recurrence of Thymoma: Clinicopathological Features, Therapy, and Prognosis

Factors influencing the recurrence or persistence of thymoma after therapy were investigated in 127 patients with thymoma, including 75 with thymoma and myasthenia gravis. The rate of recurrence or persistence was 19% (24 of 127 patients) overall, 11% (8 of 75 patients) in myasthenic thymoma, and 31% (16 of 52 patients) in nonmyasthenic thymoma. The more advanced the clinical stage, the higher the rate of recurrence or persistence. The recurrence/persistence rate for patients with the same clinical stage was higher in those with nonmyasthenic thymoma (8% in Stage I, 11% in Stage II, 36% in Stage III, and 75% in Stage IV) than in those with myasthenic thymoma (0 in Stage I, 13% in Stage II, 18% in Stage III, and 20% in Stage IV). The prognosis for patients having subtotal resection of tumor was good in myasthenic thymoma (recurrence/persistence rate, 17%) in contrast with nonmyasthenic thymoma (recurrence/persistence rate, 78%). These results suggest that nonmyasthenic thymoma is more malignant than myasthenic thymoma. Postoperative radiotherapy was effective in preventing the recurrence or persistence of thymoma after therapy.

A tentative tumor–node–metastasis classification of thymoma

To establish a tumor–node–metastasis (TNM) classification of thymoma, 207 thymoma patients seen at the First Department of Surgery, Osaka University, and the Second Department of Surgery, Nagoya City University, were evaluated. Lymphogenous and hematogenous metastases of thymoma were infrequent, but their frequency increased with the duration of the course. Lymphogenous metastasis was observed in few cases, but it was considered to progress from anterior mediastinal lymph nodes to intrathoracic and then to extrathoracic lymph nodes. No particular characteristics were observed in hematogenous metastasis. On the basis of these observations, a TNM classification of thymoma was established and applied it to 207 thymoma cases, but it had little advantage over conventional clinical staging. High percentages of thymic carcinomas and thymic carcinoids were in Stage IVB, and the TNM classification of these tumors was considered to be more useful.

Production of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human breast carcinomas.

We examined production and tissue localization of matrix metalloproteinase (MMP)‐1 (tissue collagenase), MMP‐2 (gelatinase A), MMP‐3 (stromelysin‐1), MMP‐9 (gelatinase B), tissue inhibitors of metalloproteinase (TIMP)‐1 and TIMP‐2 in human breast carcinomas. In more than half of the cases, MMP‐1, MMP‐2, MMP‐9, TIMP‐1 and TIMP‐2 were immunolocalized in carcinoma cells and MMP‐2 was on the carcinoma cell membranes as well, whereas MMP‐3 was positively stained in less than 15% of the cases. MMP‐1 staining in carcinoma cells was significantly higher in scirrhous carcinoma than in other types of carcinoma. MMP‐9 expression was remarkably higher in the carcinoma cases with lymphnode metastasis than in the non‐metastatic cases. MMP‐3 was mainly expressed in T‐lymphocytes infiltrated in the tumor stroma. Stromal fibroblasts were positive for all these MMPs except for MMP‐3. The TIMP‐1 levels released into the culture media by carcinoma tissues were significantly lower than those by fibroadenoma tissues, although there were no significant differences in the levels of MMP‐1, MMP‐2, MMP‐9 and TIMP‐2. Gelatin zymographical analyses showed that the activation rate of the zymogen of MMP‐2 (proMMP‐2) is significantly higher in the more advanced carcinoma group with lymphnode metastasis than in the metastasis‐negative and fibroadenoma groups. These data indicate that MMP‐1, MMP‐2 and MMP‐9 are highly expressed in human breast carcinoma tissue and suggest that activation of proMMP‐2 may be an indicator of lymphnode metastasis of the breast carcinoma.

Thymic neuroendocrine tumor (thymic carcinoid): a clinicopathologic study in 15 patients

BACKGROUND Thymic neuroendocrine tumor (carcinoid tumor) is rare, and prognosis for patients with this tumor has been difficult to predict. METHODS The medical records of 15 patients were reviewed, and the patients were classified according to tentative TNM classification and histologic grade. RESULTS Ten (66.7%) of 15 patients were male. Lymph node metastases were identified in 9 (60%) of 15 patients at the time of resection. There were one grade 1, nine grade 2, and five grade 3 tumors. Total resection was possible in 13 patients. Distant metastases developed in 10 (76.9%) of these 13 patients, although no local recurrence developed. Of these 10 patients, 6 died of distant metastases 5 to 25 months after the recurrence. Three patients are still alive, with metastases to the bone, spleen, and pleura 1 to 24 months after the diagnosis of recurrence. Two patients are presently tumor free (T1N0, grade 3 and T3N2, grade 2), but only 1 has survived beyond 5 years. CONCLUSIONS Thymic neuroendocrine tumor must be regarded as a malignant neoplasm that is prone to metastasize to mediastinal lymph nodes and to distant sites, even after total excision. Neither T and N classification nor histologic grade has been successful in predicting the outcome of a patient with this tumor. More aggressive management, including adjuvant therapies and reexcision of subsequent tumors, may result in increased survival.

Thymectomy and malignancy

Three hundred ninety patients who underwent thymectomy for myasthenia gravis (MG) were followed up to investigate the development of associated malignancies. There were 102 patients with thymoma and 288 without thymoma. Malignant neoplasms were detected in ten patients, four of whom already had the tumor at the time MG was diagnosed. Thus, malignancy developed after thymectomy in six patients. Malignant fibrous histiocytoma (MFH) developed in three patients, as well as gastric cancer, gastric leiomyosarcoma, rectal cancer, liver cancer, lung cancer, breast cancer, and thymic carcinoid in one patient each. Nine of the ten malignancies developed in the thymoma group, and only one in the non-thymoma group. The predicted number of patients with malignancy was 2.63 in the thymoma group and 2.65 in the non-thymoma group. Our findings suggest that the presence of thymoma facilitates the occurrence of extrathymic malignancy, and that thymectomy never enhances the occurrence of malignancy but possibly inhibits it.

COMPARISON OF THE RESULTS OF TRANSSTERNAL IMPLE, TRANSCERVICAL SIMPLE, AND EXTENDED THYMECTOMY

Recently, the effectiveness of thymectomy for myasthenia gravis (MG) has been well appreciated.2. ti, * At the start of use of thymectomies for MG, it was performed by median sternotomy, and this approach became wide-spread in most clinics of thoracic surgery. Thereafter, since the latter half of the 1960s a new approach was advocated 12, 22 in some institutes, mainly, Mt. Sinai Hospital and the Massachusetts General Hospital. This approach was the one performed by a collar incision up above the sternal notch, and the advocates of this method asserted merits of lower morbidity, and lesser surgical stress. In 1975, weI6 remarked upon the high incidence of extracapsular thymic tissue in the fat at the anterior mediastinum, and thought that the en bloc resection of fat tissue with the thymus gland was necessary to remove the thymic tissue as much as possible. Thus, in the First Surgical Department of Osaka University, three different procedures have been performed for nonthymomatous MG, i.e., 1 ) transsternal simple thymectomy from 1962 to 1970, 2) transcervical simple thymectomy from 1971 to March 1973, and 3) extended thymectomy from April 1973 up t o date. Herewith, we present a survey comparing the results using those procedures.

Staging System of Thymoma

Introduction: Thirty years have gone by since the Masaoka staging system of thymoma was proposed in 1981. Although the Masaoka staging system has been accepted by many surgeons and pathologists, some proposals of revision and improvements have been suggested. At this time, I reinvestigated the Masaoka staging system based on the recent follow-up study of the thymomas resected at Nagoya City University. Methods: Using the follow-up results of 211 thymomas in Nagoya, I analyzed the following aspects: (1) evaluation of the Masaoka staging system as a prognostic factor in the Nagoya series and (2) critical assessment of the proposals of revision to the Masaoka staging system. Results: (1) Univariate analysis showed that Masaoka stages were significantly prognostic for overall survival (p < 0.0001). (2) The difference of survivals between stage I and II was not significant, but progression-free survival of stage I was 100% for up to 20 years, whereas one tumor death case in stage II was found. (3) Differences of survival between the cases with and without great vessel invasion in stage III were not significant. (4) Prognosis of N+ tumors was yet better defined. Conclusion: (1) The Masaoka staging system remains a valuable prognostic factor. (2) Combination of stage I with II and separation of stage III into subgroups are not recommended. (3) At the moment, it is better to include N+ tumors in stage IVb.

Thymomas associated with pure red cell aplasia. Histologic and follow-up studies

Seventeen cases of pure red cell aplasia (PRCA) with thymoma were studied clinically, histologically, and immunologically. Two cases were associated with myasthenia gravis (MG), and three with hypogammaglobulinemia. Coombs test and antinucleus antibody test were positive in five cases. All thymomas were spindle cell types, and the adjacent thymuses had no germinal center, but showed epithelial clusters frequently. All patients, except one whose tumor was unresectable, had thymo‐thymomectomy. The operation was effective in six cases (37.5%), and the effects were not different between two operative procedures (simple and extended thymectomy). Myasthenic symptoms in two patients remitted after the operation, but effects on hypogammaglobulinemia were conincident with those on PRCA.