Which stages of thymoma benefit from adjuvant chemotherapy post-thymectomy?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'Which stages of thymoma benefit from adjuvant chemotherapy post thymectomy?' Altogether more than 150 papers were found using the reported search, of which only eight represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated; these studies have mainly reported the survival and recurrence rates of post-thymectomy patients who received adjuvant radiotherapy or chemoradiotherapy, and adjuvant radiotherapy alone was only used in a small group of patients in these studies. We did not find any randomized controlled trials comparing adjuvant chemotherapy with chemo/radiotherapy and, due to a very small incidence of this tumour, it is unlikely to see any trials in future. Studies were mainly retrospective or institutional reports and showed that, despite the high sensitivity of this tumour to chemotherapy agents and the use of chemotherapy as one of the main treatment modalities in the advanced stages of thymoma, current data are not supporting postoperative chemotherapy as a sole adjuvant treatment in advanced stages of thymoma. We conclude that, in patients with thymoma, surgical resection with or without radiation therapy is the gold standard treatment for early-stage disease (I and II). Adjuvant radiotherapy/chemoradiotherapy should be considered for Masaoka stage III (A and B) or above, and it is also advised to add adjuvant therapy for all patients with cortical fenestration, even in stages I and II. But there is no evidence that chemotherapy alone improves the survival in patients with completely resected stage III and IV thymomas and thymic carcinoma. In patients with extra-radiation field disease, however, the use of chemotherapy can potentially improve survival but no follow-up data on this group of patients are available.     

Therapy for thymic epithelial tumors

Thymoma is the most common tumor of the anterior mediastinum. This tumor is associated with unique paraneoplastic syndromes. The rarity of this tumor has somewhat obscured the optimal treatment for this disease. The World Health Organization classification system, which published in 1999, appears to be an advance in our understanding of thymoma. The Masaoka classification is now the most widely accepted and is an excellent predictor of the prognosis of thymoma. Now the International Thymic Malignancy Interest Group is currently engaged in the development of a validated formal TNM classification system for thymic malignancies. The optimal treatment of thymoma is performed according to its clinical stage. Surgery remains the mainstay of treatment for thymic epithelial tumors. Minimally invasive surgery including thoracoscopic surgery and robotic surgery for stage I and II thymomas is increasing now. The value of postoperative radiotherapy in completely resected stage II or III tumors is questionable. As thymomas have a moderate response rate to chemotherapy or radiotherapy, multimodality therapy involving surgery, chemotherapy and radiotherapy appears to increase the rate of complete resection and survival in the advanced (stage III and IV) thymomas.     

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.     

Results of Re-resection for Recurrent Thymomas

Background. The treatment of recurrent thymomas remains controversial.

Patients. The place for re-resection was retrospectively studied in 28 consecutive patients operated on during the last 40 years. The initial Masaoka staging of the thymoma was stage I, 4; stage II, 8; stage III, 11; and stage IVa, 3. Postoperatively, 14 have had radiation therapy, 1 chemotherapy, and 13 no adjuvant treatment. Seven patients had development of recurrences, 15 had pleuropulmonary metastases, 5 had both, and 1 had thoracotomy scar recurrence. Nineteen patients had a complete resection and 9 an incomplete one.

Results. Most local recurrences appeared after resection of stage I or II thymomas. On the other hand, in patients with stage III or IV thymomas pleural or pulmonary metastases mainly developed. No local recurrence occurred in patients who initially received postoperative radiation therapy. Five-year and 10-year survival rates were 51% and 43%, respectively, for the overall population. Among the 19 patients with complete resection, only 3 patients had a subsequent recurrence; 1 of them could be reoperated on and is still alive and free of disease.

Conclusions. Thymoma recurrences often appear as a locoregional rather than a hematogenous spread. Re-resection can be recommended in selected patients.     

Thymoma

Objective: We evaluated the prognostic factors for thymoma that remain controversial.Methods: We studied 72 consecutive patients treated for thymoma during the period between 1966 and 1997. Recurrence-free interval rates and overall survival rates calculated by the Kaplan-Meier method were compared using logrank test by the Masaoka stage, extent of surgical resection, histology, or associated disease(s). Multivariate analysis was performed using Cox's proportional hazards model.Results: Thirty-two thymomas were at Masaoka stage I, 9 at stage II, 15 at stage III, and 16 were at stage IV. There were 56 complete resections, 7 incomplete resections (2 at stage III and 5 at stage IV), and 9 biopsies (1 at stage III and 8 at stage IV). Forty-one thymomas were cortical, 16 medullary, and 15 were mixed form. Association of myasthenia gravis was found in 20 patients, and pure red cell aplasia in 7. After an average follow-up period of 103 months, the recurrence-free 5-, 10-, 15-year interval rate was 89%, 80%, 80%, respectively, and overall 5-, 10-, 15-year survival rate was 86%, 71%, 59%, respectively. Factors influencing the recurrence-free interval and overall survival included the Masaoka stage, extent of surgical resection, and association with pure red cell aplasia. Multivariate analysis revealed stage IV tumor and association with pure red cell aplasia as risk factors for recurrence. Pure red cell aplasia indicated poor prognosis for overall survival.Conclusions: Masaoka stage, extent of surgical resection, and association with pure red cell aplasia were prognostic factors for thymoma. Multidisciplinary treatment for stage IV tumors and better control of pure red cell aplasia, if associated, should be investigated.     

Thymoma

OBJECTIVE: We evaluated the prognostic factors for thymoma that remain controversial. METHODS: We studied 72 consecutive patients treated for thymoma during the period between 1966 and 1997. Recurrence-free interval rates and overall survival rates calculated by the Kaplan-Meier method were compared using log-rank test by the Masaoka stage, extent of surgical resection, histology, or associated disease(s). Multivariate analysis was performed using Cox's proportional hazards model. RESULTS: Thirty-two thymomas were at Masaoka stage I, 9 at stage II, 15 at stage III, and 16 were at stage IV. There were 56 complete resections, 7 incomplete resections (2 at stage III and 5 at stage IV), and 9 biopsies (1 at stage III and 8 at stage IV). Forty-one thymomas were cortical, 16 medullary, and 15 were mixed form. Association of myasthenia gravis was found in 20 patients, and pure red cell aplasia in 7. After an average follow-up period of 103 months, the recurrence-free 5-, 10-, 15-year interval rate was 89%, 80%, 80%, respectively, and overall 5-, 10-, 15-year survival rate was 86%, 71%, 59%, respectively. Factors influencing the recurrence-free interval and overall survival included the Masaoka stage, extent of surgical resection, and association with pure red cell aplasia. Multivariate analysis revealed stage IV tumor and association with pure red cell aplasia as risk factors for recurrence. Pure red cell aplasia indicated poor prognosis for overall survival. CONCLUSIONS: Masaoka stage, extent of surgical resection, and association with pure red cell aplasia were prognostic factors for thymoma. Multidisciplinary treatment for stage IV tumors and better control of pure red cell aplasia, if associated, should be investigated.     

Results from surgical treatment for thymoma. 43 years of experience.

OBJECTIVE: The biological behavior of thymoma and its prognosis after surgical intervention remain still controversial. The efficacy of surgical treatment for thymoma was investigated by examining long-term follow-up data. SUBJECTS AND METHODS: Follow-up data for patients undergoing surgical resection of histopathologically-confirmed thymoma between 1954 and 1997 were obtained and were retrospectively analyzed. Clinical staging was based on Masaoka's staging system, and histological classification on Rosai's proposed criteria. RESULTS: Data for 140 patients were collected. Sixty-four patients had stage I, 32 had stage II, 28 had stage III, and 16 had stage IV thymoma. There were significant differences in survival between patients with stage I and stage III, stage I and stage IV and stage II and stage III disease, but not between those with stage I thymoma and stage II thymoma. No significant difference in survival was observed between the 56 patients with myasthenia gravis (MG) and the 84 without MG. The 38 patients classified as having a predominantly-epithelial thymoma had a poorer prognosis than the 41 with a predominantly-lymphocytic thymoma. Until 1975, there were four patients with stage I thymomas who later showed recurrence, compared with 21 among those with stage II, III and IV diseases. Since 1976, extended thymectomy with thymomectomy under median sternotomy has been adopted as the standard operation for a thymoma, and there has been no recurrence in stage I patients. CONCLUSIONS: Patients with stage III or IV invasive thymoma have a poorer prognosis and a higher recurrence rate than those with encapsulated thymoma, and patients with a predominantly-epithelial thymoma have a poorer prognosis than those with a predominantly-lymphocytic thymoma. Extended thymectomy with thymomectomy under median sternotomy can be considered as adequate treatment for a stage I thymoma. Myasthenia gravis does not appear to affect the prognosis of patients with a thymoma.     

Treatment of thymomas. A report of 67 cases.

From 1979 to 1989, 126 patients were treated for thymic tumors. Of these, 67 (53%) had thymomas occurring in 27 men and 40 women; the mean age was 46 years: 24 patients had no symptoms and myasthenia gravis was present in 21 cases. A complete resection was performed in 45 patients, associated in 22 with postoperative adjuvant treatment (radiotherapy, 2; radio- and chemotherapy, 20). Two patients had a partial resection followed by radiotherapy and chemotherapy. Twenty patients had initially only a biopsy and were treated by irradiation in 3 cases, radio- plus chemotherapy in 16, radio- plus chemotherapy and subsequent resection in 1 case. The staging was carried out according to the GETT Classification (stage I A:26; I B:6; II:12; III A:1; III B:18; IVA:4). Thymomas were found to be of predominant epithelial type in 12 cases, predominantly lymphocytic type in 9, and mixed in 46. No recurrence occurred after complete resection. The overall 10-year survival was 71.1%. A good correlation was found according to staging: 96% in stage I; 80% in stage II; 35% in stage III. Presence of myasthenia gravis did not affect the results. The best prognostic factor remains complete resection with postoperative radiotherapy to prevent recurrences. The role of adjuvant chemotherapy needs further evaluation.     

Spindle cell and mixed spindle/lymphocytic thymomas: an integrated clinicopathologic and immunohistochemical study of 81 cases

Forty-three cases of spindle cell thymoma (medullary, WHO type A) and 38 cases of mixed spindle/lymphocytic thymoma (WHO type AB) were studied for their clinicopathologic and immunohistochemical characteristics. Three histologic patterns of spindle cell thymoma were observed: short-spindled (57%), long-spindled (31%), and micronodular (12%). The short-spindled variant was composed of oval to short spindle cells commonly arranged in a hemangiopericytic or microcystic pattern. The long-spindled variant chiefly consisted of fibroblast-like epithelial cells mimicking fibrohistiocytic neoplasms. The micronodular variant was characterized by small nests of short spindle cells dispersed among a lymphoid stroma with frequent germinal centers. All kinds of spindle cell could be admixed with lymphocyte-rich "cortex"-like areas to constitute mixed spindle/lymphocytic thymomas. Immunohistochemically, the epithelial cells in up to 70% of the short-spindled and long-spindled variants of spindle cell thymoma and 90% of mixed spindle/lymphocytic thymomas were positive for CD20, whereas the epithelial cells in all micronodular spindle cell thymomas were negative. All of the spindle cell thymomas and most of the mixed spindle/lymphocytic thymomas in this study were found in stages I and II. Follow up of the patients did not disclose relapse or mortality directly resulting from the tumors. However, the prognosis of stage I and II spindle cell and mixed spindle/lymphocytic thymomas did not significantly differ from those of stage I and II thymomas of other types by a stage-matched survival analysis. Our data showed that spindle cell and mixed spindle/lymphocytic thymomas are distinctive in histologic pattern and immunohistochemical profile. When interpreted within the context of staging, spindle cell and mixed spindle/lymphocytic thymomas presenting in stages I and II most likely behave in an indolent fashion.     

Thymoma needs a new staging system

Despite the wide use of the Masaoka staging system for thymoma, the distribution of survival by stage group is not well balanced. The new staging systems for testing were defined as follows: stage I was created by merging Masaoka's stages I and II, and stage IV remained unchanged. Stages II and III were defined as thymomas with invasive growth and the following combinations of tumor diameter and number of involved structures/organs. Scheme 1: stage II included tumors less than 10 cm in diameter and involving one neighboring structure/organ. Stage III included tumors with all combinations of diameter and number of involved structures/organs other than those in stage II. Scheme 2: stage II included tumors of all combinations other than those in stage III. Stage III included tumors 10 cm or more in diameter and involving two or more structures/organs. The survival curves were assessed for 138 patients treated at the National Cancer Center, Tokyo. The 10-year survival rates for each stage according to the Masaoka, Scheme 1, and Scheme 2 systems were as follows: stage I (100%, 100%, 100%), stage II (100%, 86%, 83%), stage III (70%, 64%, 34%), and stage IV (34%, 34%, 34%), respectively. The survival curves for Scheme 1 gave the most balanced distribution of survival in each staging group. By considering both tumor diameter and number of involved structures/organs, Masaoka's stages I-III could be rearranged with more balanced distribution of survival.     

侵袭性胸腺瘤手术治疗预后因素的随访

目的 观察侵袭性胸腺瘤的手术治疗效果,并分析影响患者预后的相关因素.方法 回顾性分析2000年1月至2009年12月接受手术治疗的59例侵袭性胸腺瘤患者的临床及随访资料.患者为连续病例,男性34例,女性25例;年龄18～72岁,平均49岁.根治性手术44例,姑息切除或活检15例.Masaoka分期:Ⅱ期18例,Ⅲ期30例,Ⅳ期11例;Ⅱ期患者术后未接受辅助放疗或化疗,Ⅲ、Ⅳ期患者术后接受辅助放疗和(或)化疗26例,未接受辅助放疗或化疗15例.分析手术方式、Masaoka分期、辅助放疗和(或)化疗与患者预后的关系.结果 本组59例患者随访时间1～111个月,平均54个月;失访3例,失访率6.1%.全组局部复发或全身转移19例,死亡14例,3年、5年生存率分别为86.8%、70.8%.单因素分析显示接受完全性切除手术、Masaoka分期较早及术后接受辅助放疗和(或)化疗的患者有较高的生存率(P＜0.05).多因素分析显示是否完全性切除、术后接受辅助放疗和(或)化疗是影响患者预后的独立因素(P＜0.05).结论 Masaoka分期与侵袭性胸腺瘤患者预后相关;完全性切除手术及术后辅助放化疗可显著提高患者生存率;部分复发患者再次手术后亦可获得长期生存.     

胸腺瘤与胸腺瘤合并重症肌无力的临床探讨

目的　探讨胸腺瘤 (TT)及胸腺瘤合并重症肌无力 (TTMG)的临床特点。方法　对 2 2年间外科治疗的TT 2 5 8例 ,其中单纯TT 16 8例 (组 1) ,TTMG 90例 (组 2 )的临床特点进行对比分析。结果　组 1平均年龄 38 4岁 ,93 4%的病人肿瘤直径大于 5cm ,病理分期多为III、IV期 (6 1 2 % )。组 2平均年龄 46 2岁 ,肿瘤直径 5cm以下占 6 5 6 % ,5 5 2 %为病理I期。结论　早期胸腺瘤诊断标准为 :肿瘤直径<3cm和病理分期I期 ;TTMG的特征是肌无力 (MG)的症状重、病史短、症状进展快、胸腺危象的发生率高。     

Clinical and pathologic predictors of survival in patients with thymic tumors

BACKGROUND: The aim of this study is to evaluate the impact of thymectomy in patients with thymic neoplasms and to identify clinical and histopathological factors associated with improved long-term outcome of surgery. METHODS: We treated 74 patients between February 1987 and July 1993. There were 29 total and 36 simple thymectomies. These last cases, all non-myasthenic, had benign thymomas (n=30) but 6 had thymic carcinomas. Nine tumors were no-resected (5 thymomas and 4 thymic carcinomas). Minimum follow-up by Department of Thoracic Surgery Istituto Nazionale Tumori was 60 months after thymectomy. We divided the specimens according to Marino and Muller-Hermelink's classification: 54 thymomas, 18 thymic carcinomas and 2 no-diagnosis specify thymomas. There were 53 stage I, 1 stage II, 13 stage III, 5 stage IVa and 2 stage IVb according to Masaoka. RESULTS: Forty-six patients with treated thymoma were alive without disease at the end of follow-up, the remaining 8 died from recurrence in 6, a new tumor in 1 and a heart attack in the last. Of 18 thymic carcinomas 9 were alive at the end of follow-up (1 with recurrence), only 4 dead from recurrence. The actuarial survival of patients with thymomas was 88.5% at 5 years, (73.6% in cortical type, 85.7% in medullary type, 93.9% in mixed type, 100% in predominantly cortical type). Myasthenia gravis didn't influence the survival: 87.3 (no MG) vs 90%. Advanced stage thymomas significantly increased the risk of death from early stage I: 32.4 vs 100% at 5 years. In thymic carcinoma patients with well-differentiated thymic carcinoma (WDTC) died less than others: the actuarial probability of survival at 5 years was 90 vs 68%. CONCLUSIONS: Thymectomy was the best treatment to long term outcome. In our experience, survival was related to histotype and to local extension of tumor.     

Thymoma--a retrospective study of 48 cases

Of the 48 thymomas operated on between 1968 and 1985 50% were associated with myasthenia gravis, in 25% diagnosis was made due to accidental X-ray findings. In the staging according to Masaoka et al. [10] the following distribution was noted: I:22, II:5, III:18, IV:3. The 5-year survival rate of the 37 curatively resected patients was 78.5% (stage I: 88.6%, stage III: 55.6%). No stage III patient with residual tumor survived more than 2 years. Predominantly epithelial tumors had a significantly worse prognosis as compared to those with lymphocytic predominance. None of the 4 patients with category II thymoma survived more than 15 months. Association with myasthenia proved to have a negative prognostic influence in stage I and II patients. Frequency of local recurrences and metastases is documented. The value of irradiation and chemotherapy is discussed.     

Treatment of recurrent thymic tumors

Surgery is the cornerstone of therapy for recurrent thymic tumors. The pattern of recurrence is, however, less defined. Between 1966 and 1988, we operated on 83 patients with thymoma, 11 of whom underwent surgery for recurrence (group I). In 1989, we initiated a prospective multimodality protocol and have enrolled 128 patients with 9 (7%) recurrences since (group II). In group I, 1 patient was originally at stage I, 2 were at stage II, 5 at stage III, and 3 at stage IV. The patients underwent 1 (#10) or 2 (#1) reoperations and 5 showed histological progression of malignancy. One patient died postoperatively, 6 died of disease, and 3 are alive and disease free 18 to 22 years after the first operation. In group 2, no patient was originally at stage I, 1 was at stage II, 4 were at stage III, and 4 at stage IV. Reoperation (5 patients) was followed by chemotherapy and 2 showed histological progression of disease. One patient died after 2 years, and 4 patients are alive after 6 to 11 years. All recurrent tumors were thymomas with cortical differentiation. Early onset of recurrence was a negative prognostic factor. Thymomas can recur also at early stages. A multimodality approach is indicated also for early stage lesions based on histology.     

Adjuvant radiotherapy after complete resection of thymoma.

Seventy patients were studied after undergoing complete resection of thymoma to determine the effect of postoperative adjuvant mediastinal radiotherapy on prognosis, with regard to clinical stage, histological type, and pleural factor. Pleural factor was defined as follows: p0, no adhesion to the mediastinal pleura; p1, fibrous adhesion to the mediastinal pleura without microscopic invasion; and p2, microscopic invasion of the mediastinal pleura. Recurrence of thymoma after complete resection was observed in 13 patients, 12 (92%) with pleural dissemination, 6 (46%) with local recurrence, and 2 (15%) with distant metastasis (types of recurrence are overlapping). In stage I and stage II p0 patients, no recurrence was observed, regardless of mediastinal radiotherapy. Whereas mediastinal irradiation completely prevented recurrence in stage II p1 patients, 4 (36.4%) nonirradiated stage II p1 patients experienced recurrence. In stage II p2 patients, 75% had pleural dissemination even after radiotherapy. A high incidence of recurrence was also observed in stage III, nonirradiated (25%) and irradiated (30%) patients. The results suggest that mediastinal irradiation for stage I and II p0 patients is not always necessary, and that therapy for stage II p1 is essential and also expected to decrease the recurrence rate. On the other hand, in stage II p2 and stage III thymomas, mediastinal irradiation is not sufficient to prevent pleural recurrence even after complete resection. Our classification based on pleural factor is useful for better selection of appropriate postoperative treatment for thymoma patients.     

Lympho-epithelial thymomas. A retrospective study of 88 resections

Of 113 lympho-epithelial thymomas retrospectively studied, 56 were epithelial, 20 lymphocytic, 30 mixed and 7 were undefined forms. There were 88 resections (20 stage I, 47 stage II, 13 stage III and 8 stage IV). There were 69 primary resections (followed by radiotherapy in 54 cases) of which 57 were complete and 12 were incomplete. There were 19 secondary resections after radiotherapy: 10 were complete and 9 were incomplete and 25 patients were not operated upon and were treated by radio- and chemotherapy. After primary resection, the actuarial 5-year survival is 64.07% and the 10-year survival is 50.86%. After a secondary resection, the 5 year-survival is 43.74%. After non-surgical treatment, it is 18.67%. After surgery, the prognostic importance of staging is confirmed as more important than the cellular structure. Myasthenic patients are subject to late accidents. Postoperative radiotherapy seems to be justified, but its effect is not statistically significant when resection is complete. Post-radiotherapy surgery is beneficial only in cases of complete resection. The metastatic evolution of thymomas has been underrated and seems to depend upon the local control of the tumour. The use of chemotherapy remains to be defined.     

Long-term outcome after multimodality treatment for stage III thymic tumors

BACKGROUND: Surgery remains the cornerstone of therapy for thymic tumors, but the optimal treatment for advanced, infiltrative lesions is still controversial. The introduction of multimodality protocols has substantially modified survival and recurrence rate. We reviewed our 13-year prospective experience with multimodality treatment of stage III thymoma and thymic carcinoma. METHODS: Since 1989 we have prospectively used a multimodality approach in 45 stage III thymic tumors. Sixteen patients (35%) had myasthenia gravis. Twenty-three patients (51%) had pure or predominantly cortical thymoma (group 1), 11 (24.5%) had well-differentiated thymic carcinoma (group 2), and 11 (24.5%) had thymic carcinoma (group 3). Tumors that were not considered radically resectable at preoperative workup underwent biopsy and induction chemotherapy (15 patients, 33%) followed by surgical resection; all patients were referred for adjuvant chemoradiotherapy. RESULTS: No operative mortality was recorded; 1 treatment-related death during adjuvant chemotherapy was observed in group 1. Complete resection was feasible in 91% of patients in groups 1 and 2 and 82% in group 3. The overall 10-year survival was 78%. Ten-year survival for groups 1 and 2 was 90% and 85%, respectively; 8-year survival for group 3 was 56%. During follow-up, tumor recurrence was noted in 3 patients (13%) from group 1, 3 (27%) from group 2, and 3 (27%) from group 3. CONCLUSIONS: Multimodality treatment with induction chemotherapy (when required) and adjuvant chemoradiotherapy offers encouraging results for stage III thymic tumors; the outcome is more favorable for cortical thymoma and well-differentiated thymic carcinoma.     

Tumors of the thymus and thymic region: I. Clinicopathological studies on thymomas

A series of 43 patients with thymoma was reviewed. The patients were classified with respect to some factors of prognostic significance. The tumors were reclassified histologically, and a staging system with three defined stage-groups was applied to the series on the basis of operative findings and histological examination of surgical specimens. Surgical-pathological staging is of high prognostic and therapeutic importance in thymomas. Complete removal of the tumor was possible in the 25 patients with stage I or II disease and in 14 of the 18 patients with stage III tumors. Pleural metastases were observed in half of the patients with stage III disease. Even patients with extensive local spread or pleural metastases were subject to tumor resection. The treatment of choice is radical resection along in stage I; radical extirpation and, if indicated, postoperative radiotherapy in stage II; and radical resection whenever possible, even in cases of pleural spread, in stage III, with postoperative radiotherapy and chemotherapy. Myasthenia gravis is an indication rather than a contraindication to radical treatment of thymoma, although some patients may deterioratte. The importance of total thymectomy is stressed.     

Management of myasthenia gravis in association with thymoma

From June 1975 to March 2002, we experienced 339 patients with myasthenia gravis (MG). Ninety-four patients (81 generalized MG and 13 ocular type) had associated with thymoma. Extended thymectomy including thymoma was performed in all patients. The thymomas were classified as stage I (n = 46), II (n = 31), III (n = 14), and IV a (n = 3). Histopathological findings of the thymoma indicated polygonal cell type in 75 cases, mixture of polygonal and spindle cell type in 14, and spindle cell type in 3, respectively. Three cases in stage II, 12 in III, and 3 in IV a received postoperative radiation therapy. Twenty-two patients required prolonged respirator management for respiratory crisis. Complete remission of MG was seen in 15 cases (17%), and good therapeutic results were obtained in 55 cases (58%) with combined corticosteroid therapy. On the other hand, recurrences of the invasive thymoma were seen in 12 cases (13%), and six of them (6%) died of the tumor. In conclusion, early extended thymectomy including thymoma is markedly effective therapy for MG associated with thymoma, although careful attention should be paid for recurrence of the invasive thymoma.