"Maximal" thymectomy for myasthenia gravis. Results

Thymectomy has been shown to be effective in the treatment of myasthenia gravis. The logical goal of operation has been complete removal of the thymus, but there has been controversy about the surgical technique and its relation to results. Surgical-anatomic studies have shown gross and microscopic thymus widely distributed in the neck and mediastinum. We believe that an en bloc transcervical-transsternal "maximal" thymectomy is required to remove all thymic tissue predictably. Ninety-five patients with generalized myasthenia gravis underwent "maximal" thymectomy consecutively between 1977 and 1985 and were evaluated 6 months to 89 months after operation. In Group A (N = 72), myasthenia gravis without thymoma, the uncorrected data revealed that 96% (69) had benefited from operation: 79% (57) had no symptoms; 46% (33) were in remission; 33% (24) were symptom free when receiving minimal doses of pyridostigmine; and none were worse. Life table analysis yielded a remission rate of 81% at 89 months. In group B (N = 8), myasthenia gravis without thymoma for which patients underwent reexploration for incapacitating weakness after earlier transcervical or transsternal operations, residual thymus was found in all. One patient was in remission, two were symptom free when receiving medication, one was unchanged, and none were worse. In group C (N 15), myasthenia gravis and thymoma, two patients were in remission and nine were symptom free when receiving medication. Two patients in this group died 2 and 4 years postoperatively in crisis. Response to thymectomy in group A was greater in patients with mild myasthenia gravis and may have been better in patients who had symptoms for less than 60 months preoperatively, but the response did not depend on age, sex, presence or absence of thymic hyperplasia or involution, or titers of acetylcholine receptor antibodies. The response to thymectomy in group B was striking but slower than in group A, perhaps because symptoms were more severe and of longer duration. The response in group C was also less good than in group A and proportionately fewer benefited. These results support the recommendation for thymectomy in the treatment of patients with generalized myasthenia gravis and indicate the desirability of a maximal procedure. For persistent or recurrent severe symptoms after previous transcervical or submaximal transsternal resections, reoperation by this technique is also recommended.     

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.     

Clinical and pathologic predictors of outcome in thymoma-associated myasthenia gravis

BACKGROUND: Myasthenia gravis is by far the most common paraneoplastic syndrome of thymomas. There is little information regarding the influence of clinical variables and thymoma-associated factors on biologic development of myasthenia gravis. The aim of the study was to determine independent predictors of clinical outcome in thymoma with myasthenia gravis. METHODS: We studied 108 patients with thymoma-associated myasthenia gravis undergoing removal of the mediastinal mass between 1967 and 2000. Clinical and pathologic variables associated with clinical outcome of myasthenia were assessed by multivariate Cox regression analysis. RESULTS: Patients were followed for a mean period of 10 years (9 months to 33 years). A total of 38 patients died (35.2%), in 14 cases (37%) because of myasthenia gravis and in 6 (16%) because of recurrence of thymoma. With respect to clinical outcome of myasthenia gravis, at the end of the follow-up period, the rate of remission was 16% (n = 17). Of the 91 patients in whom remission was not achieved, 55 had no symptoms with immunosuppressive medication and 36 had symptoms with medication. CONCLUSIONS: In patients with thymoma-associated myasthenia gravis, well-differentiated thymic carcinoma (Müller-Hermelink system), age more than 55 years, and interval from the onset of symptoms to thymectomy of less than 1 year were found to be independent predictors of nonremission of myasthenia gravis after thymectomy.     

Transcervical thymectomy for myasthenia gravis achieves results comparable to thymectomy by sternotomy

BACKGROUND: It remains controversial whether transcervical thymectomy offers results equivalent to thymectomy by way of a median sternotomy in the treatment of myasthenia gravis. Furthermore, preoperative prognostic factors have not been clearly defined. METHODS: This study is a retrospective chart review and interview of 78 patients completing transcervical thymectomy for myasthenia gravis between 1992 and 1999. RESULTS: There were 24 men and 54 women. Mean age was 40 years (range, 13 to 78 years). Twelve patients were in Osserman class 1, 25 in class 2, 30 in class 3, and 11 in class 4 (mean, 2.5). There was no perioperative mortality and 6 (7.7%) morbidities. Mean length of stay was 1.5 days and mean follow-up, 54.6 months. The crude cumulative complete remission (asymptomatic off medications for 6 months) rate was 39.7% (n = 31). Only 8 patients (10.3%) failed to improve after transcervical thymectomy. Kaplan-Meier estimates of complete remission were 31% and 43% at 2 and 5 years, respectively. Eight patients with thymoma had a 5-year estimated complete remission rate of 75% in contrast to 43% in 38 patients with thymic hyperplasia and 36% in 32 patients with neither thymoma nor hyperplasia (p = 0.01). Twelve patients with ocular myasthenia had a 5-year estimated complete remission rate of 57%, whereas patients with mild-to-moderate (n = 55) or severe (n = 11) generalized symptoms had 5-year complete remission rates of 43% and 30%, respectively (p = 0.21). CONCLUSIONS: Overall, extended transcervical thymectomy offers results that are comparable to those published for the transsternal procedure. Patients with milder disease (including isolated ocular disease) and taking no preoperative immunosuppressive agents appear to experience higher remission rates. In contrast to previous studies, we also find that small thymomas predict better responses to thymectomy.     

Thymectomy in the treatment of ocular myasthenia gravis

BACKGROUND: Thymectomy is an effective and accepted treatment for myasthenia gravis, but thymectomy for ocular myasthenia gravis (Osserman stage I) is controversial. OBJECTIVE: To assess the efficacy and propriety of thymectomy for the treatment of ocular myasthenia gravis. METHODS: We conducted a review and follow-up of all patients who had thymectomy for the treatment of ocular myasthenia gravis between 1970 and 1998 at the University of California, Davis, Medical Center, and the University of Rome, "La Sapienza," Rome, Italy. Patient response to thymectomy was categorized as follows: cured, patients who became symptom-free and required no further medication; improved, patients who required less medication and whose symptoms were less severe; unchanged, patients whose symptoms and medications were the same; worse, patients who had more severe symptoms, needed more medication, or died. RESULTS: Sixty-one patients (mean age 37 years; range 14-73 years) were followed up for a mean duration of 9 years (range 0.5-29 years). Ocular myasthenia gravis with mixed and cortical thymomas, stages I to IV, occurred in 12 patients, and ocular myasthenia without thymomas occurred in 49 patients. Transsternal thymectomy (n = 55) and transcervical thymectomy (n = 6) resulted in cure in 31 (51%) patients, improvement in 12 (20%) patients, no change in 16 (26%) patients, and worsening of symptoms (including 1 postoperative death) in 2 patients. Patient outcomes were statistically independent of the duration of preoperative symptoms (mean 9.5 months), patient age, or the presence or absence of thymoma. In patients with ocular myasthenia, 70% were cured or improved after thymectomy; in the subgroup of patients with ocular myasthenia and thymoma, 67% were cured or improved. CONCLUSION: Thymectomy is an effective and safe treatment for patients with ocular myasthenia gravis.     

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.     

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.     

A case of a small thymoma associated with myasthenia gravis in which the tumor was reduced by corticosteroid therapy]

The case in this study was a 34-year-old male with a small thymoma associated with myasthenia gravis. The patient had been treated with corticosteroids for 10 months against myasthenia gravis. During the course of the treatment a chest CT revealed that the tumor had reduced. Thereafter the extended thymectomy was performed. A close examination of the excised thymus revealed the presence of a flat cystic tumor measuring 1.5 x 0.8 x 0.5 cm at the site corresponding to the CT image. This tumor was histologically ascertained to be a thymoma. The thymoma is sensitive to corticosteroids, which can effectively reduce it. As conclusion, it is necessary to check thoroughly on the presence of thymoma prior to the initiation of corticosteroid therapy to treat myasthenia gravis.     

Two cases of post-thymectomy myasthenia gravis]

The first patient was a 37-year-old man with an invasive and lymphoid cell dominant thymoma (stage III). He underwent extended total thymectomy and partial resection of the upper lobe of the left lung. Four years after the operation, he had ptosis and diplopia and was diagnosed as having myasthenia gravis (positive Tensilon test and raised antiacetylcholine receptor antibody titer). His symptoms improved with the steroid therapy. The second patient was a 37-year-old woman with an invasive and mixed type thymoma (stage III). Extended total thymectomy with combined resection of the mediastinal pleura and right phrenic nerve was performed, but the tumor recurred in the right thorax 2 years postoperatively. Subtotal resection of the parietal pleura and recurrent tumors was performed by right thoracotomy, and steroid therapy was given. She developed malaise, ptosis and diplopia three months later, and was diagnosed as having myasthenia gravis. Her symptoms disappeared after the steroid therapy was stopped. A review of the Japanese literature is presented and problems regarding the pathogenesis of this disease are discussed.     

Notice from the American Board of Thoracic Surgery

Sixty-five patients with thymomatous myasthenia gravis were investigated. Thymomas were present in 44% of the male patients and 19% of the female patients with myasthenia gravis. The incidence of thymomatous disease in male patients was higher than in female patients in all age groups. Eighty percent of men more than 50 years old and women more than 60 years old had myasthenia gravis with thymoma. Germinal center formation in the thymus of patients with thymomatous myasthenia gravis was positive in 91% and was high grade.The prognosis for patients undergoing extended thymectomy of thymomatous myasthenia gravis was significantly better than in those having transsternal simple thymectomy, but it was worse than the prognosis for patients with nonthymomatous myasthenia gravis. No increase in the rate of remission or palliation was seen one year after thymectomy. It is concluded that early thymectomy is effective in control of myasthenia gravis in thymomatous myasthenia gravis.     

Appearance of thymoma 15 years after extended thymectomy for myasthenia gravis without thymoma.

Several cases of thymoma recurrence after resection have been reported. However, thymoma appearance following an extended thymectomy for non-thymomatous myasthenia gravis is very rare. We report a case of thymoma in a 48-year-old woman, 15 years after an extended thymectomy for non-thymomatous myasthenia gravis. The importance of a complete dissection of mediastinal adipose tissue during the extended thymectomy as well as careful follow-up for such patients is also noted.     

Thymectomy for myasthenia gravis in children

Myasthenia gravis is rare in childhood. In the last 12 years, we have treated eight children under 16 years of age for this disease. There were six girls and two boys, a ratio of 3:1. Age of presentation of symptoms ranged from 10 to 16 years (mean 11 3/4). There was no significant family history and there were no significant associated diseases. Antibodies were measured in six patients and were all negative. All patients were given cholinergic drugs and five had corticosteroids as well. Three underwent tracheostomies because of severe respiratory insufficiency. There was clinical deterioration or no improvement in spite of increasing doses of medication; hence, thymectomy was performed in all after an average duration of symptoms of 12 months (range 4 to 17). All thymectomies were done through median sternotomy. There was no postoperative morbidity or mortality. No thymoma was found. Four had lymphoid hyperplasia, in three, the thymus looked normal and in one it looked very atrophic. Dramatic amelioration with eventual complete recovery was seen in six, with an average follow-up of 7.3 years (3 to 11) after thymectomy. Two patients are only one year after thymectomy and are improving progressively. We recommend early thymectomy in myasthenia gravis of childhood on the basis of very encouraging results.     

同期双侧单孔胸腔镜手术治疗胸腺瘤合并重症肌无力

目的探讨同期双侧单孔胸腔镜下胸腺扩大切除术的可行性及早期手术效果。方法2017年8月~2019年6月,对20例胸腺瘤合并重症肌无力行同期双侧单孔胸腔镜下胸腺扩大切除术。切口位于腋前线和腋中线之间第4肋间,长3 cm。结果手术均顺利完成,手术时间(183.2±27.8)min,术中失血量(36.0±27.2)ml,胸腔引流时间(3.9±1.1)d,术后住院时间(6.1±1.4)d,病理测量瘤体最大径(4.3±1.3)cm。无围手术期并发症。Masaoka分期Ⅰ期2例,Ⅱ期16例,Ⅲ期2例(B2型和B3型各1例)。20例随访2~24个月,中位数14个月,总体缓解率90%(18/20)。结论同期双侧单孔胸腔镜下胸腺扩大切除术治疗胸腺瘤合并重症肌无力,手术安全,近期效果满意。     

Management of patients with malignant thymoma

This report documents the results of therapy in 23 patients treated for malignant thymoma between 1944 and 1979. Of the group, 22 patients had neoplasms which invaded mediastinal structures; six had distant metastases. Four patients had myasthenia gravis and one had erythroid hypoplasia associated with collagen vascular disease. No deaths were associated with primary therapy, which included an operative procedure in all cases. Follow-up ranged from 4 months to 18 years (mean 5.63 +/- 1.03 years, SEM). Fifteen patients died, with postoperative survival times ranging from 4 months to 18 years (mean 3.8 +/- 1.27 years). Five patients were alive without recurrence from 3 to 11 years postoperatively (mean 6.8 +/- 1.36 years), and three patients were alive with recurrence or distant metastases from 4 to 17 years postoperatively (mean 10.75 +/- 2.66 years). Differences in survival on the basis of tumor cell type were not statistically significant. Therapeutic groups were analyzed for 5 year survivors, tumor deaths within 5 years of therapy, deaths due to other causes, deaths due to tumor after 5 years, those presently alive, and longest known survivor. The data suggest that complete surgical excision offers the best chance of long-term survival when compared to partial resection plus irradiation (p less than 0.05). No statistical significance could be demonstrated between the groups who had complete resection with versus without postoperative irradiation. There also was no statistically significant difference between the group of patients receiving irradiation following partial excision of most of their tumor and the group receiving irradiation following only biopsy of the lesion. This observation suggests there is no value in so-called "debulking procedures" and suggests that irradiation may be of value in local control of thymoma. Perpetual surveillance is necessary since late recurrence is common.     

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。     

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.     

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。     

Role of thymectomy in the surgical treatment of myasthenia gravis

Of the 26 patients with myasthenia gravis undergone thymectomy, 11 cases had either benign or malignant thymoma as judged not only by hitological examination but also by their clinical and operative findings. Age of initial onset ranged from 13 to 64 years old. Fifteen out of 26 (58 per cent) benefited from thymectomy. Duration of the symptom from the onset to the operation and the presence or absence of the thymoma are not related to their outcome. Benign or malignant nature of thymoma should not be determined by histological examination alone but by combined evaluation of clinical and operative findings. Serial studies of serum immunoglobulin levels before and after thymectomy suggested that this disorder could be associated with humoral antibody (IgG). HLA typing of the patients with myasthenia gravis did not indicate the presence of any specific antigens.     

Thymoma is associated with relapse of symptoms after transsternal thymectomy for myasthenia gravis

Thymectomy is considered a therapeutic option for patients with myasthenia gravis. A myasthenic patient who has not received any treatment for years and shows no signs or symptoms of the disease after operation is still susceptible to a recurrence of myasthenic symptoms. To investigate which factors are related to relapse of symptoms in patients having thymectomy, we conduct a retrospective review in the patients who had experienced complete remission after thymectomy. Complete remission was achieved in 92 of 154 patients who received extended transsternal thymectomy for myasthenia gravis. Among these 92 patients, 20 patients had relapse of symptoms and needed medication again after complete remission was achieved (21.7%). Ten of 22 patients in the thymomatous group had relapse of symptom after complete remission was achieved, while only 10 of 70 patients in the nonthymomatous group had relapse of symptom (P=0.006). Multivariate Cox regression analysis revealed that thymoma was an independent factor for the development of relapse of symptoms. In conclusion, thymoma is an adverse prognostic factor for the MG patients who have experienced complete remission after thymectomy. The patients with thymoma had a greater possibility to develop relapse of symptoms than the patients without thymoma.     

Extended thymectomy and intraoperative-intrapleural perfusion hyperthermo-chemotherapy for stage IVa invasive thymoma with myasthenia gravis

A 37-year-old woman diagnosed with ocular myasthenia gravis was referred to our department. Chest computed tomography (CT) showed anterior mediastinal tumor and right pleural dissemination. Extended thymectomy and right intraoperative-intrapleural perfusion hyperthermo-chemothrapy (IPHC) were performed. Pathological diagnosis was invasive thymoma type B2 and stage IVa based on Masaoka's classification. The post operative course was uneventful. The patient underwent 4 cycles of adjuvant chemotherapy with doxorubicin, cisplatin, vincristine, and cyclophosphamide (ADOC), and is free from recurrence at 12 months postoperatively.