重症肌无力合并胸腺瘤的外科治疗(附31例报告)

报告１９８０年至１９９６年１０月手术治疗３１例重症肌无力合并胸腺瘤的结果。３１例占同期手术治疗１２０例重症肌无力之２５．８％。按Ｍａｓａｏｋａ分期属Ｉ期７例，Ｉ期８例，ＩＩ期１５例，ＩＶ期１例，术后１５例发生危象，均采用气管切开及辅助呼吸，１例死于危象。随访半年至８年，平均３７个月，５年内死亡６例，其中ＩＩ期４例，Ｉ期２例。结论：重症肌无力合并胸腺瘤术后危象的发生率远较未合并胸腺瘤者高，及时气管切开行辅助呼吸是处理的关键；胸腺瘤的Ｍａｓａｏｋａ病理分期与预后明显相关，肌无力的严重程度对预后亦有重要影响     

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.     

J. Maxwell Chamberlain Memorial Paper. Role of staging in prognosis and management of thymoma

Eighty-five patients operated on for thymoma from 1972 to 1989 were evaluated, 32 with myasthenia gravis and 53 without. Masaoka staging revealed stage I disease in 45 (53%), stage II in 23 (27%), stage III in 14 (16%), and stage IVa in 3 (4%). There was no operative mortality. Actuarial survival at 10 years was 63.7% for all patients: 78.3% for those in stage I, 74.7% for those in stage II, and 20.8% for those in stage III. There was no recurrence in patients in stage I. Mediastinal recurrence developed in 4 patients in stage II considered to have noninvasive disease by the surgeon. It is recommended that all patients be followed up for a minimum of 10 years and that all patients in stages II and III receive postoperative radiotherapy. The presence of myasthenia gravis is no longer considered as an adverse factor in survival.     

Expanded indications for transcervical thymectomy in the management of anterior mediastinal masses

BACKGROUND: Transcervical thymectomy (TCT) is an accepted though controversial approach for thymectomy in myasthenia gravis (MG). The suggestion of thymoma on computed tomography (CT) has been considered a contraindication to TCT. We sought to determine whether the indications for TCT could be safely expanded to include selected patients with thymomas as well as other types of anterior mediastinal masses. METHODS: Between January 1992 and September 1999, we performed 121 TCTs: 98 in patients with MG and 23 in patients without MG. The patients' records were retrospectively reviewed. RESULTS: Among the 98 MG patients, 28 had CT scans suspicious for thymoma. Of these, 14 had a thymoma pathologically. These were classified as stage I (5), stage II (8), and stage III (1). Five patients required extension of the incision for completion of the procedure. There have been no thymoma recurrences to date with a mean follow-up of 48 months (range 3 to 96 months). In the 23 patients without MG, 12 had new anterior mediastinal masses, 4 had a history of treated lymphoma, 1 had a history of treated germ cell tumor, and 6 had suspected mediastinal parathyroid adenoma. Diagnostic tissue was obtained in all patients undergoing the procedure for diagnosis, and in 4 of 6 patients, a parathyroid adenoma was successfully resected. CONCLUSIONS: Transcervical exploration and thymectomy offers a less invasive approach to the diagnosis and/or definitive treatment of selected anterior mediastinal masses. We suggest that it is appropriate to expand its use to several clinical scenarios beyond the typical indication of thymectomy in MG patients without thymoma.     

Surgical treatment of thymoma.

OBJECTIVE: To describe experience with the surgical treatment of thymoma. DESIGN: A retrospective study. Setting: A teaching hospital at the University of Ottawa. PATIENTS: Over 25 years, 42 consecutive patients (22 men, 20 women) who had a thymoma requiring operation. INTERVENTIONS: Thymectomy. OUTCOME MEASURES: Age, sex, association with myasthenia gravis, presence of a paraneoplastic syndrome, extent of surgical resection, tumour size, histologic features of the tumour, clinical staging of the thymoma and short- and long-term outcome after surgery. RESULTS: The mean (and standard deviation) age of the patients was 52.8 (12.5) years. Thirteen patients had myasthenia gravis. With respect to tumour staging, 24 patients had stage I, 7 had stage II and 11 had stage III disease. Three patients were lost to follow-up. Radiotherapy was used as an adjunct to surgical treatment in 83% of patients with stages II and III disease. Fifty-one percent of patients available for follow-up survived 175.1 months, and the cumulative 5- and 10-year overall survival rates were 87.3% and 81.4% respectively. Only 1 patient died of metastatic thymoma. Complete or partial remission of myasthenia gravis was seen in 10 (77%) affected patients. Mixed cellular histologic features and a tumour size of less than 115 cm3 were more commonly seen with stage I disease. CONCLUSIONS: Thymomas are characterized by slow growth and prolonged survival even in patients with invasive disease as long as the tumour is resected completely and treatment is accompanied by radiotherapy.     

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.     

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.     

Synchronous multiple thymoma: Report of three cases

We report three cases of synchronous multiple thymoma diagnosed at a single hospital during the 10 years since 1999. Two were accompanied by myasthenia gravis (MG). In two patients, two thymomas were detected by preoperative computed tomography (CT), and in one, a microthymoma was found incidentally on pathologic examination of a resected specimen for gross thymoma and thymus. The multiple lesions were located in the thymus, and extended thymectomy was performed via median sternotomy in all three patients. The World Health Organization subtypes of the multiple thymomas were identical in each patient; however, all were considered to be primary lesions since the larger one was well encapsulated and each tumor was apparently separated. The Masaoka stage was classified as I/I, I/I, and I/II, respectively. Postoperative clinical courses were uneventful and no recurrence was observed in any of the patients. We reviewed 16 reported cases of synchronous multiple thymoma, and discuss the pathogenesis and treatment of this unusual entity.     

Results and problems of thymectomy in myasthenia gravis over 65 years old

From June 1975 to March 1999, 300 cases of myasthenia gravis (MG) have undergone thymectomy. Twenty-eight patients over 65 years old were examined, focusing on the relationship between clinical appearances and microscopic findings of the thymuses. Among these cases, six were classified as ocular type (one case with thymoma) and 22 generalized type (eight cases with thymoma). According to the thymoma registering stages defined by Masaoka and colleagues, those nine cases with thymoma associated with stages I (n = 7), II (n = 1) and III (n = 1), respectively. The case of stage III (74 year old female) died four years and eight months after surgery. The case of stage II died of old age two years after the surgery. Complete remission was achieved in two cases of stage I. The follicular hyperplasia were seen in eight cases, and all resulted in improvement. Nine cases with no particular findings of thymuses classified into four ocular type and five generalized type including one fulminating type. Post-operative course of all these cases were uneventful. Although one recurrent of the thymoma and one death of the tumor were observed, post-operative outcomes of these elderly patients were generally satisfactory. We concluded that there is an operative indication of thymectomy for MG of even elderly patients, if no particular findings were recognized in the thymus.     

Infrasternal mediastinoscopic surgery for anterior mediastinal masses

Background Infrasternal mediastinoscopic surgery is a new alternative to the thoracoscopic approach for patients with anterior mediastinal masses.Methods We applied this technique to 18 thymectomies, one thymomectomy, and one cystectomy in a total of 20 patients with anterior mediastinal masses and then assessed the surgical results.Results Infrasternal mediastinoscopic surgery was accomplished in 18 of the 20 patients (90%). The pathological diagnoses included 13 Masaoka stage I thymomas, one stage II thymoma, two stage III thymomas, one thymic cyst, one pericardial cyst, one thymic granuloma, and one mature teratoma. Two patients with stage III thymoma required conversion to sternotomy, one for invasion into the innominate vein and the other for invasion into the pericardium. There was no surgically related mortality or complications in any patients.Conclusion Infrasternal mediastinoscopic surgery is safe and feasible for stage I thymoma and other benign tumors in the anterior mediastinum.     

横断胸骨扩大胸腺切除治疗全身型重症肌无力

目的探讨经横断胸骨入路行扩大胸腺切除治疗重症肌无力的临床疗效。了解该入路的特点及临床疗效有助于该领域胸外科医师在临床实践中进行更好的临床决策。 方法对1998至2008年在复旦大学附属华山医院胸心外科行横断胸骨治疗全身型重症肌无力的211例患者的临床资料进行回顾性研究,分析患者术中和术后基本情况。并对术后5年进行随访的患者根据是否合并胸腺瘤进行分组,采用χ²检验比较两组间的疗效。 结果经横断胸骨入路能满足对合并Masaoka-Koga Ⅰ期及Ⅱ期胸腺瘤患者及无瘤患者实施扩大胸腺切除的需要,手术并发症较低,便于围术期护理,恢复迅速。对173例患者进行术后5年随访,总缓解率达到79.8%(138/173),无肿瘤复发。合并胸腺瘤组的总缓解率为81.9%(59/72),未合并胸腺瘤组的总缓解率为78.2%(79/101),两组间比较差异无统计学意义(χ²＝0.362,P＝0.548)。 结论与其他常用手术入路相比,横断胸骨入路的特点值得该领域胸外科医师关注。     

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.     

经颈部切口全胸腺切除术13例

目的探讨经颈部切口的全胸腺切除术治疗前纵隔胸腺内小病灶的临床应用价值。方法2007年3月～2011年12月行经颈部切口全胸腺切除术13例,使用常规手术器械及头灯照明,经颈横切口从胸骨后间隙完整游离肿瘤及全胸腺并切除。结果1例因游离中发现侵犯左无名静脉中转胸骨正中切口切除肿瘤。12例经颈部切口全胸腺切除术平均手术时间48．1min（38—60min）,平均术中出血量45ml（30～50m1）,平均术后住院3．7d（2～7d）。1例术后第2天出现房颤,药物治疗后转窦性心率。13例均无手术相关性死亡。术后病理：MasaokaI期胸腺瘤2例,Ⅱ期胸腺瘤3例,Ⅲ期胸腺瘤1例,胸腺增生3例,胸腺脂肪瘤、胸腺囊肿、异位甲状旁腺囊肿、巨大淋巴结增生各1例。5例MasaokaI／Ⅱ期胸腺瘤术后均未行放化疗,随访3～57个月均存活,未见肿瘤复发;1例MasaokaⅢ期胸腺瘤术后放疗50Gy,随访14个月,无复发;胸腺增生3例术后症状均明显改善,随访14～28个月均完全缓解;其余4例良性胸腺肿瘤随访31—59个月,均存活,未见肿瘤复发。结论经颈部切口的全胸腺切除术治疗前纵隔胸腺内早期小病灶是安全可行的。对于合并胸腺内病变的早期重症肌无力患者及≤5cm的MasaokaI／Ⅱ期胸腺瘤患者的手术确切疗效有待于进一步病例数的积累。     

Surgical approach in thymectomy: Our experience and review of the literature

AimThymectomy is the main treatment for thymoma and patients with myasthenia gravis (MG). The traditional approach is through a median sternotomy, but, recently, thymectomy through minimally invasive approaches is increasingly performed. Our purpose is an analysis and discussion of the clinical presentation, the diagnostic procedures and the surgical technique. We also consider post-operative complications and results, over a period of 5 years (May 2011–June 2016), in thymic masses admitted in our Thoracic Surgery Unit.MethodsWe analyzed 8 patients who underwent surgical treatment for thymic masses over a period of 5 years. 6 patients (75%) had thymoma, 2 patients (25%) had thymic carcinomas. 2 patients with thymoma (33%) had myasthenia gravis. We performed a complete surgical resection with median sternotomy as standard approach.ResultsOne patient (12%) died in the postoperative period. The histological study revealed 6 (75%) thymoma and 2 (25%) thymic carcinomas. Post-operative morbidity occurred in 2 patients (25%) and were: pneumonia in 1 case (12%), atrial fibrillation and pleural effusion in 2 patients (25%). One patient with thymoma type A recurred at skeletal muscle 2-years after surgery.ConclusionsThymic malignancies are rare tumors. Surgical resection is the main treatment, but a multimodal approach is useful for many patients. Radical thymectomy is completed removing all the soft tissue in the anterior mediastinum between the two phrenic nerves and this is the most important factor in controlling myasthenia and influencing survival in patients with thymoma. Open (median sternotomy) approach has been the standard approach for thymectomy for the better visualization of the anatomical structures. Actually, video-assisted thoracoscopic surgery (VATS) thymectomy and robotic video-assisted thoracoscopic (R-VATS) approach versus open surgery has an equal if not superior oncological efficacy, better perioperative complications and survival outcomes.     

扩大胸腺切除治疗重症肌无力的结果分析

目的：总结1990年2月至1999年10月手术治疗重症肌无力的随访结果，并分析其预后因素。方法：54例病人均行扩大胸腺切除术，按改良Osserman标准分为I型15例，Ⅱa型14例，Ⅱb型16例，Ⅲ型9例，随访结果按完全缓解，改善，无效，差进行评价。结果：手术后完全缓解29．6％，改善48．1％，无效13．0％，差9．3％，手术疗效与术前病程长短及Osserman分型有关，与性别，年龄，胸腺病理类型无关，结论：扩大胸腺切除术是治疗重症肌无力的有效方法，对重症肌无力病人应及早手术治疗。     

Experience in the treatment of acute fulminating myasthenia gravis]

During past 15 years, 188 myasthenia gravis (MG) patients underwent thymomectomy or thymectomy with extended resection of the adipose tissue around the thymus in our institution. Four of 188 patients (2%) had to be given respiratory support within 2 months after the onset of MG. We defined this MG as the acute fulminating type. There were 2 male and 2 female patients, ranging in age from 22 to 44 years (average, 32.5 years). Three of these patients had thymoma. One of these patients was post-thymomectomy myasthenia gravis and another patient was d-penicillamine induced myasthenia gravis. Two patients admitted on respirator for respiratory crisis. All patients underwent operation within 2 weeks after admission. The duration of respiratory support ranged from 10 to 120 days (mean 44) after operation. The period of the hospital stay ranged from 8 months to 2 years 1 month (mean 1 year 5 months). During acute stage after operation, the patients needed ACTH, steroid, immunosuppressants (azathioprine, Bredinin) and plasma pheresis depending on their severity of myasthenic symptoms. In 2 patients dose of steroid could be reduced without deterioration of the symptoms. They are doing well with small dose of steroid. In one patient plasma pheresis was performed 6 years after thymectomy. Various symptoms due to myasthenia gravis and rheumatoid arthritis has recurred 10 years after thymectomy. The titer of acetylcholine receptor antibody of this patient has been continuing in high level.     

Myasthenia gravis in elderly patients

The clinical features and the effect of thymectomy were compared between 27 elderly patients (Group 2) and 119 young adult patients (Group 1) with myasthenia gravis (MG). In the elderly group, MG was type I in 3 patients, type IIA in 6, type IIB in 17, and type III in 1; and in the young group, type I in 6, type IIA in 36, type IIB in 73, and type III in 4. The association rate with autoimmune disease in patients without thymoma was 12.5% (1/8) in Group 2 and 21.3% (20/94) in Group 1. Autoimmune diseases were not seen in any patients with thymoma. The clinical stage of thymoma was not significantly different between the two groups. The rates of remission and of palliation at 3 years after thymectomy were 18.2% and 72.7%, respectively, in Group 2 patients with thymoma, 21.4% and 78.6% in Group 1 patients with thymoma, 50% and 100% in Group 2 patients without thymoma, and 50% and 98.1% in Group 1 patients without thymoma.     

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.     

Multimodality Treatment of Thymoma: A Prospective Study

Background. Thymomas are a heterogeneous group of tumors. Treatment of invasive lesions is not well standardized. The aim of this study is to propose a clinicopathologically based protocol for multimodality therapy.

Methods. Between 1965 and 1988, we operated on 83 patients with thymoma who did not receive standardized adjuvant therapy. In 1989, on the basis of the retrospective analysis of the data, we started a multimodality therapy protocol and used it for 65 patients. Twelve patients had medullary thymoma (11 stage I and 1 stage II), 13 had mixed type (6 stage I and 7 stage II), and 40 had cortical thymoma (4 stage I, 11 stage II, 12 stage III, and 13 stage IV). We considered three groups. Group I (n = 18 patients), benign thymoma, included stage I and II medullary and stage I mixed thymomas; radical resection with no adjuvant therapy was performed. Group II (n = 22), invasive thymoma, included stage I and II cortical and stage II mixed thymomas; postoperative chemotherapy plus radiotherapy was always administered. Group III (n = 25), malignant thymoma, comprised stage III and IV cortical thymomas and stage III mixed thymomas; resectable stage III lesions were removed, and highly invasive stage III and stage IV lesions underwent biopsy, neoadjuvant chemotherapy, and surgical resection; postoperative chemotherapy and radiotherapy was administered to all patients.

Results. The 8-year survival rate for patients in stages I, II, III, and IV was 95%, 100%, 92%, and 68%, respectively. Patients with medullary thymoma had a 92% 8-year survival rate; those with mixed type, 100%; and those with cortical thymoma, 85%. Group I had an 8-year survival rate of 94%; group II, 100%; and group III, 76%. Survival was compared with that of patients operated on before 1989: differences were not significant for group I; survival improved in group II (100% versus 81%; p = not significant); and group III showed significant improvement (76% versus 43%; p < 0.049).

Conclusions. Multimodality treatment with neoadjuvant chemotherapy and adjuvant chemotherapy plus radiotherapy may improve the results of radical resection and the survival of patients with invasive and malignant thymoma.     

Recurrent thymoma in patients with myasthenia gravis

One hundred sixty-six patients underwent operation for myasthenia gravis between 1977 and 1989. Thirty-eight patients had associated thymoma, registering stages I (n = 17), II (n = 9), III (n = 11), and IVa (n = 1) according to the classification of Masaoka and colleagues. Extended thymectomy was performed on 128 patients without thymoma; thymothymectomy, with resection of the anterior mediastinal fat and tissues adherent to the tumor, was performed in all patients with thymoma. There were no instances of early or late death. Neuromuscular function improved, and clinical myasthenic symptoms stabilized in almost all patients except 2 patients in stage III and 1 patient in stage IVa, who had an exacerbation of the myasthenic symptoms associated with recurrence of thymoma. All the recurrent tumors were on the pleura and could be resected. The suspected cause of recurrence is either dissemination of tumor cells as a result of operative manipulation or undetected disseminated foci that existed at the time of the first operation. The resections of the recurrent invasive thymomas localized on the pleura were easily performed and improved the myasthenic symptoms.