Ann Thorac Surg 1999;67:1563-1567
© 1999 The Society of Thoracic Surgeons
Original Articles
Efficacy and safety of extended thymectomy for elderly patients with myasthenia gravis
Masanori Tsuchida, MDa,
Yasushi Yamato, MDa,
Takahiro Souma, MDa,
Katsuo Yoshiya, MDa,
Takehiro Watanabe, MDa,
Tadashi Aoki, MDa,
Jun-ichi Hayashi, MDa
a Department of Thoracic and Cardiovascular Surgery, Niigata University School of Medicine, Niigata, Japan
Accepted for publication December 22, 1998.
Address reprint requests to Dr Tsuchida, Department of Thoracic and Cardiovascular Surgery, Niigata University School of Medicine, 1-757 Asahimachi-dori, 951-8510, Japan
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Abstract
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Background. The number of elderly patients who are diagnosed as myasthenia gravis (MG) is increasing in Japan. Although several factors affecting thymectomy have been well documented, few studies have focused on the efficacy and safety of thymectomy for elderly patients older than 60 years.
Methods. We evaluated 94 patients with MG who underwent extended thymectomy, and divided them into two groups: patients younger than 59 years and patients older than 60 years. Preoperative patient data, pathology of the thymus, complications, and clinical outcome were evaluated.
Results. In 69 young patients and 25 elderly patients, we observed no significant differences between the two groups with regard to preoperative data. Thymic hyperplasia was present in 45% of the young group and 16% of the elderly group. Remission and improvement rate were 40% and 57% in the young group and 8% and 75% in the elderly group, respectively. There were no serious complications, except one early death due to gastrointestinal bleeding in the elderly group.
Conclusions. We conclude that thymectomy is a safe and effective alternative for elderly patients with MG.
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Introduction
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Myasthenia gravis (MG) is a chronic autoimmune disease for which thymectomy is considered the most effective treatment for achieving sustained improvement as well as remission. Several factors affecting the patient’s response to thymectomy have been reported [1–5]. Because different reports have contained heterogeneous populations of patients, results did not entirely agree. However, most studies identified milder preoperative Osserman stage [1], thymic histology [3, 4] (absence of thymoma and presence of germinal center), and shorter symptom duration [5] as better prognostic predictors. Concerning the issue of age, disagreement remains as to whether thymectomy should be performed for elderly patients [6, 7]. Although several studies have recommended thymectomy for elderly patients, these studies included relatively young patients of 40 to 50 years of age [8–10] whereas, the age distribution of MG is bimodal, with peaks at 10–20 and 60–70 years. Furthermore, precise data concerning complications and medical requirements after thymectomy in elderly patients have not been reported. Because the number of elderly patients who are diagnosed as MG is increasing in Japan, and surgeons are often consulted for surgery for those patients, we evaluated the efficacy and safety of thymectomy for elderly patients older than 60 years.
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Material and methods
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Ninety-four patients with MG who underwent extended thymectomy at our hospital between 1985 and 1996 were evaluated in this study. The distribution of these patients according to age and gender at the time of operation, as well as age and thymic abnormality distributions, is shown in Figures 1 and 2. In all patients, diagnosis was based on clinical signs and symptoms, a positive response to edrophomium-chloride, and electromyography test. Each patient underwent clinical staging based on a modified Osserman’s classification [11]. Indications for surgical therapy included generalized MG and persistent ocular type under appropriate medications. In all patients, extended thymectomies were performed through median sternotomy, and entire anterior mediastinal fat including the thymus was removed from the midpericardium inferiorly, inferior aspect of thyroid grand superiorly, and each phrenic nerve laterally.
Postoperative medication was administered by neurologists. Antichorinesterase was given when patients showed any myasthenic symptoms after thymectomy. Corticosteroid was administered to those patients whose diseases’ preoperative severity was more than IIA and had persistent symptoms after thymectomy. Patients who had contraindication of steroid usage, such as the presence of tuberculosis or peptic ulcer, were excluded from steroid therapy. About 1 month after surgery, patients requiring treatment were started on an alternative day dose of 40 mg, which was gradually increased to 100 mg (2 mg/kg), maintained for 4–8 weeks, and then tapered off slowly. For the purpose of this study, patients were divided into two groups: patients aged younger than 59 years and patients aged older than 60 years. As preoperative data, clinical forms, medication requirements, duration of symptoms, and antibody titer to acethylcholine receptor were evaluated. After surgery, time to extubation, pathology of the thymus, complications, and medication requirements were evaluated as well as long-term outcome. Clinical outcome was evaluated at least 1 year after thymectomy. The mean duration of the follow-up period was 84.4 months in the young group and 52.8 months in the elderly group. To evaluate clinical improvement, the most recent follow-up information gathered by physician examination was obtained on 67 of 69 young patients (97%) and 24 of 25 elderly patients (96%). The criteria for the evaluation were as follows: remission, no symptoms without any medication, improvement, no or fewer symptoms with the same or less medication, worse, same symptom with more medication, or deterioration of disease. Statistical analysis of the data was done using 
2 test, and a p value of less than 0.05 was considered significant.
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Results
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Table 1 summarizes preoperative patient data from both groups. There were no significant differences between two groups regarding any preoperative data. Medication was required in 54 of 69 patients in the young group and 20 of 25 patients in the elderly group. Most patients required anticholinesterase alone to control their symptoms. In the young group, one patient who was unresponsive to medication was treated with plasmapheresis before surgery. All patients underwent extended thymectomy under general anesthesia. Table 2 summarizes the pathology of the thymus in both groups. Whereas hyperplasia was the most common finding in the young group, only 4 patients (16%) in the elderly group showed hyperplasia. Thymoma was present in 22 of the 69 in the young group and 10 of 25 in the elderly group. There was a significant difference between the two groups regarding the pathological findings. In the patients who had thymoma, 3 patients in the young group and 4 patients in the elderly group required excision of the pericardium, portion of the lung, innominate vein, or the superior vena cava in order to obtain an adequate surgical margin. The clinical stages according to Masaoka’s classification were also summarized in Table 2. To prevent local recurrence, postoperative radiation was given to all of the stage IV invasive thymomas in both groups. In most cases, extubation was accomplished in the operating room or recovery room after careful observation.
Postoperative respiratory support was required in 3 of the young group and in 6 of the elderly group. In the patients who required respiratory support, all except one in the elderly group had respiratory symptoms before surgery. In addition, 1 patient in the young group and 5 patients in the elderly group had thymoma. One patient in the young group and 3 patients in the elderly group required prolonged respiratory support for more than 1 month. One superficial wound infection was seen in the young group.
After thymectomy, 8 patients in the young group and 2 patients in the elderly group required no medication at all. Sixteen patients in the young group and 4 patients in the elderly group required anticholinesterase alone.
The remaining patients were given cortecosteroid-based medication after thymectomy. Corticosteroid was weaned from 34% of the young patients and 16% of the elderly patients. In the remaining patients of both groups, corticosteroid was tapered, and most patients received 10 mg or less of predonisolone every other day.
The clinical outcome and medication requirements at the last follow-up date for both groups are summarized in Table 3. There was one death in the young group and three deaths in the elderly group. A 39-year-old man with invasive thymoma died of arrhythmia 21 months after thymectomy. His symptoms deteriorated after thymectomy and he was treated with corticosteroid, cyclophosphamide, and plasmapheresis. In the elderly group, one early death was due to steroid-induced acute gastrointestinal bleeding 1 month after surgery. This patient required excision of the superior vena cava and innominate vein. The excised great vessels were reconstructed with grafts, and anticoagulant therapy was given postoperatively. One patient died of sepsis 10 years after thymectomy, and another patient died of heart failure 5 years after thymectomy. Neither of the latter 2 patients had any symptoms at the time of death.
In the young group, 27 were in remission and 38 showed improvement. Only one patient showed deterioration due to disease. In the elderly group, 2 patients were in remission and 18 showed improvement. The remission rate was 40% in the young group and 8% in the elderly group. At the last follow-up date, patient status was symptom free in 49 patients, MG type I in 11 patients, type IIA in 5 patients, and type IIB in 1 patient in the young group. In the elderly group, 15 patients were free from symptoms, 3 patients were type I, 2 patients were type IIA, and 1 patient was type IIB (Fig 3). Thymectomy’s overall benefit for both groups was 97% in the young group and 83% in the elderly group. Table 4 shows 10 patients aged older than 70 who underwent thymectomy. It is important to recognize that 5 of 6 nonthymomatous patients aged older than 70 achieved improvement with no complications.
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Fig 3. Relationship between the pathology of the thymuses and the clinical outcome. One early death and two late deaths were excluded.
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Comment
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Although thymectomy has been accepted as a therapeutic alternative for patients with MG, there is still a question regarding choosing candidates for thymectomy. It is not clear if there is an upper age limit. Perlo and associates examined the thymus obtained from 20 autopsy patients older than 60 years, and found no or only involuted thymic tissue microscopically. [12] They concluded that thymectomy should not be recommended for elderly patients. In general, it has been suggested that 40 to 50 years of age was a reasonable cutoff, [13] but surgeons have performed many successful thymectomies on patients in their sixth to seventh decade of life. Because the number of patients with MG is increasing with the increase in the elderly population in Japan, [14] it is important to evaluate the safety and efficacy of thymectomy for those patients. In this study, we have demonstrated that thymectomy is a safe and effective alternative even for the elderly patients with MG. Recent literature describing the performance of transsternal thymectomy reported that the remission rates ranged from 28% to 42%, and the improvement rates ranged from 58% to 94%. [7,15–17] In the current study, the young patient group achieved a remission rate of 40% and an improvement rate of 57%, which were in line with the results of other reports. On the other hand, in the elderly patient group, only 8% achieved remission. However, 75% of patients achieved improvement with some medication, and only one deterioration was observed. Overall benefit rate from thymectomy in the elderly group was 83%. However, our present study does not support that thymectomy alone contributes to the improvement of symptoms, because most patients were treated with steroids after thymectomy. Many patients who were not administered steroid preoperatively were administered steroid at the time of the evaluation of the efficacy of the operation. In elderly patients who were treated with steroids, 16% of patients were weaned off steroids, and in the remaining 84% of patients, steroid treatment was tapered at the last follow-up date. Therefore, the evaluation of the operation is very complicated. However, this high improvement rate may not be brought about by medication alone, and we believe that thymectomy is effective for the elderly patients. A randomized trial comparing surgery with other medical treatment would be ideal, but it is unlikely to be performed, because even in the young population there are no prospective, randomized studies that prove thymectomy is effective in MG.
Although postoperative steroid usage is controversial, several reports support the beneficial effect of predonisone, [18] and we are in favor of this supplementary treatment after thymectomy when the early result of thymectomy was not entirely satisfactory. In addition, elderly patients are less likely to tolerate complications associated with both progression of the disease and a high dose of medication to control symptoms. It would be reasonable to treat patients with some combination of strategies to give them the best chance for cure.
In general, the thymus undergoes progressive involution after puberty and the functional tissue is replaced by fat. It may lead us to ask why thymectomy is effective for the elderly patients who have atrophic or involuted thymuses. Masaoka and Monden [19] demonstrated that an extended thymectomy, which resects all the anterior mediastinal fat tissue including the thymus, is superior to thymectomy alone with regard to the clinical outcome, and that thymic remnants outside the thymus also play an important role in MG. We believe this may be true in the elderly thymus, in which a few epithelial cells and lymphocytes are still present. Nussbaum and associates [16] reported that half of the patients who achieved remission had either normal or involuted thymuses. In fact, in our current study, thymic pathology did not correlate with the clinical outcome (Fig 3).
Concerning complications associated with surgery, no major complications were seen except one early death due to steroid-induced gastrointestinal bleeding. There was no sternal wound infection. Respiratory support was required for 3 of 69 young patients and 6 of 25 elderly patients. All were eventually weaned from the respirator. From our experience, we consider the patients with invasive thymoma and preoperative bulbar symptoms as possible candidates for prolonged mechanical ventilation after thymectomy.
Because thymoma is considered a potential malignancy, there may be no controversies for surgery even for elderly patients with thymomatous MG. On the other hand, the indications for thymectomy in nonthymomatous elderly patients with MG remain controversial. In our present study, 13 of 15 nonthymomatous patients in the elderly group (87%) benefited from operation. One patient remained with the same symptoms after additional medication and 1 patient without MG symptoms died of acute heart failure 5 years after surgery. There were no complications associated with thymectomy including the need of postoperative ventiratory support. Based on these observations, we encourage all patients, regardless of age or thymus status, to proceed with thymectomy as soon as possible to give them the best chance for remission. However, elderly patients may require supplementary medication after thymectomy because their remission rate is not high.
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Acknowledgments
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We acknowledge the following doctors for providing patients’ data: Tukasa Oono, MD, Hiroyuki Tanabe, MD, Ryoko Koike, MD, Nobuyoshi Fukuhara, MD, Masaki Sahara, MD, Yutaka Saitoh, MD, Masahisa Satoh, MD, Keiko Tanaka, MD, Aki Saitoh, MD, Masaki Isoda, MD, Takashi Motegi, MD, Noriyuki Tan-no, MD, Kenji Aoki, MD, Jirou Idezuki, MD, Yoshiaki Honma, MD, Masami Tanaka, MD, Hajime Tanaka, MD, Takashi Koide, MD, Takeo Kuwabara, MD, Kazuhiro Sanpei, MD, and Toshikazu Anezaki, MD.
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Abstract
Introduction
