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Ann Thorac Surg 1996;62:853-859
© 1996 The Society of Thoracic Surgeons
Second Department of Surgery, Nagoya City University Medical School, Nagoya, First Department of Surgery, Osaka University Medical School, Osaka, and Second Department of Surgery, Tokushima University Medical School, Tokushima, Japan
Accepted for publication April 24, 1996.
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Abstract |
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Methods. Three hundred seventy-five patients with myasthenia gravis (286 nonthymomatous and 89 thymomatous) who have undergone extended thymectomies were reviewed. The status of the patients was evaluated as follows: A (remission), B (improvement), C (no change), D (deterioration), E (death due to myasthenia gravis). Evaluation was performed at 3 and 6 months, and at 1, 3, 5, 10, 15, and 20 years. The effectiveness of the operation was estimated by the remission rate (RR = A/Total number of patients evaluated) and the palliation rate (PR = A + B/Total number of patients evaluated) at each point.
Results. Remission rates of the nonthymomatous patients were 15.2% (3 months), 15.9% (6 months), 22.4% (1 year), 36.9% (3 years), 45.8% (5 years), 55.7% (10 years), 67.2% (15 years), and 50.0% (20 years). Remission rates in the thymomatous patients were 13.6% (3 months), 17.5% (6 months), 27.5% (1 year), 32.4% (3 years), 23.0% (5 years), 30.0% (10 years), 31.8% (15 years), and 37.5% (20 years). Absence of thymoma, younger age, and short duration of the disease were favorable prognostic factors. Thymectomy was effective also in patients with ocular myasthenia gravis. Preoperative steroid administration did not improve the outcome.
Conclusions. Extended thymectomy is an excellent operative procedure for myasthenia gravis in both nonthymomatous and thymomatous patients.
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Introduction |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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Material and Methods |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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. All patients of stage I and II underwent extended operation. In stage III patients, 23 of 25 were treated by total resection of the thymoma with invaded adjacent structures. In these patients, extended thymectomy was performed. However, 2 patients treated with exploratory thoracotomy were not subjects of extended thymectomy. In stage IVa, all 6 patients (2 subtotal, 3 partial resections of tumor, and 1 exploratory thoracotomy) were also not subjects of extended thymectomy. One patient, classified "uncertified" had undergone an operation in another institute, and received a second operation for recurrent tumor in our institution. Accordingly, 375 patients with MG (286 nonthymomatous and 89 thymomatous) who have undergone extended thymectomy and are the subject of this review.
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Statistical Analysis
Differences of RRs or PRs in different groups were analyzed by 
2 test or two-tailed test, and significance of difference was judged by p values less than 0.05.
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Results |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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. In the nonthymomatous group, a peak in the 20- to 40-year-old group was found. The mean age was 35.0 years: men, 38.3 years, and women, 33.9 years. The sex distribution revealed predominance in women. On the other hand, the mean age of the thymomatous patients was 44.0 years: men, 43.1 years, and women, 45.1 years. The sex distribution was equivalent.
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. Type IIb disease was most common, followed in order by IIa and I. Type III was rare. Distribution patterns in the nonthymomatous and the thymomatous group were quite similar. In the thymomatous group, correlations of stage of thymoma and MG type were investigated (Table 4). There was no significant correlation between MG type and stage of thymoma.
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The titer of acetylcholine receptor antibody was measured by the anti-human IgG method [4]. Mean values of titers in the nonthymomatous (55.6 ± 124.9 pmol/mL) and the thymomatous group (67.3 ± 201.7 pmol/mL) did not differ. The titers were higher in women than in men, respectively in both groups.
The patients were divided into two groups based on preoperative steroid treatment. In the nonthymomatous group, there were 255 preoperative steroid-negative and 31 preoperative steroid-positive patients. In the thymomatous group, only 4 patients received preoperative steroid therapy. Although various protocols were used in steroid administration, differences in the administration protocols were ignored because they were too multifarious. There was no marked bias in the distribution of MG types between the two groups.
Follow-up Results
Two hundred eighty-four patients (99.3%) in the nonthymomatous and 89 patients (100%) in the thymomatous group were followed up.
There was no operative death. Twenty-nine patients died: 14 patients (4.9%) in the nonthymomatous and 15 patients (16.9%) in the thymomatous group. Eleven patients died because of MG: 5 in the nonthymomatous and 6 in the thymomatous group. Deaths due to malignancies were found only in the thymomatous group (5 patients).
In the nonthymomatous group, the number of patients at each evaluation, and the RRs and PRs are shown in Table 5 and Figure 2. The RR curve rose gradually, reached a peak of 67.2% at 15 years, and dropped at 20 years. The PR curve reached 74% at 3 months, then increased gradually until year 3, and plateaued over 90% thereafter. In the thymomatous group, the RR rose gradually, reached 32.4% at 3 years, and plateaued (Table 6 and Fig 3). The PR curve reached 82.5% at 1 year, and plateaued. The RRs of the nonthymomatous group exceed those of the thymomatous group after 5 years (p < 0.01 at 5, 10, and 15 years). The PRs of the nonthymomatous group exceed those of the thymomatous group at some points of evaluation (p < 0.01 at 3 and 15 years, p < 0.05 at 3 months and 10 years).
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For the age at the time of operation we compared the results of the younger group (34 years or less, 147 patients) and the older group (35 years or more, 139 patients) in the nonthymomatous patients (Fig 4). Results in the younger group were superior (significant at 6 months and 1, 3, and 5 years). In the thymomatous group, the results of 44 patients (39 years and younger) and 45 patients (40 years and older) were compared (Fig 5). Similar tendency was observed, but not significant.
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). The results were superior in the short duration group. There were significant differences at 6 months and 1, 3, 5, and 10 years. In the thymomatous patients, the RRs in shorter group (6 months or less, n = 45) were also superior than those in longer group (Fig 7).
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. The RRs in type I were not lower than those of type IIa and type IIb. The RRs in type IIa and type IIb were similar. There was no difference between 3 types. In type III, no patient reached remission. In the thymomatous group, the RRs in type I were best, and those in type IIa followed (Fig 9). The results in type IIa and III were worst (significant between I and IIa at 3 and 6 months; between I and IIb at 3 and 6 months and 1, 3, and 5 years).
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In the nonthymomatous group, outcomes of the patients who did not receive preoperative steroids (the untreated group, n = 255) and the patients who did receive preoperative steroids (the treated group, n = 31) were compared. The RRs of both groups showed no difference at any point. Such comparison was not performed in the thymomatous group because of the minimal number of steroid-treated patients.
For the stage of the thymoma, in the thymomatous group, the RRs in the patients with stage I (n = 39), II (n = 27), and III (n = 23) thymomas were compared. There was no difference between them.
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Comment |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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Transcervical thymectomy was first advocated in 1966 by the Mount Sinai Hospital group. However, the final report of Papatestas and colleagues (1987) [7] on 788 nonthymomatous patients who had undergone this procedure revealed that RR at 5 years was 23%. Those results are obviously inferior to ours. Some successors modified this procedure, or changed to the use of other procedures [5, 8, 9].
We performed transsternal simple thymectomy from 1962 to 1970, transcervical simple thymectomy from 1971 to March 1973, and extended thymectomy since April 1973 [5]. Maggi and co-workers [8] (662 patients) performed cervical thymectomy from 1973 to 1977, transsternal thymectomy from 1978 to 1982, and combined transcervical/transsternal thymectomy with resection of adipose tissue thereafter. Evoli and colleagues [9] (247 patients) performed cervical thymectomy until 1980, and thereafter transsternal thymectomy with radical excision of anterior mediastinal fat. Now, many surgeons perform the extended thymectomy.
The RRs in our nonthymoma MG patients continued to rise even after 5 years (45.9% at 5 years, 55.8% at 10 years, 68.4% at 15 years). The PRs were stable after 3 years (91.6% at 3 years, 92.3% at 5 years, 95.2% at 10 years, and 98.2% at 15 years). The results of the series by Mulder and co-workers [10] (333 patients) were similar with those of our series. The RR in 249 patients followed up for more than 8 years was 51%, and the PR was 87%. On the other hand, the RR in 84 patients followed up less than 8 years was 36%, and the PR was 80%. These data suggest that the longer the postoperative period, the better the results. Their procedure of choice was the extended thymectomy. In Maggi and associates' series [8], the RR was 37.9% and the PR was 87.3% in the nonthymoma group. Their results differ somewhat from ours. One factor may be that their series included cervical thymectomies.
A particular finding in our series is the drop of RR at 20 years. Analysis clarified that the drop was due to unfavorable results in the patients operated in 1973 to 1974. The reason might be unrefinement of technique in the early period.
Thymomas associated with MG have some special characteristics [2]. First, their histologic types are almost entirely limited to the polygonal cell type. Second, most of their clinical stages are early, compared with those of non-MG thymomas. The percentage of stage I and II was 67.3% in this series. In our previous study [2], the percentage of stage I and II was 37.8% in non-MG thymomas. Also in Maggi and associates' series [8] (162 patients), a similar distribution of stage was reported: stage I, 54.9%; II, 21.6%; III, 19.7%; and IVa, 3.7%. This finding suggests early detection of thymoma due to MG symptoms.
Distribution of MG type in the thymomatous patients was coincident with that in the nonthymomatous patients. Maggi and colleagues [8] reported similar finding. There was no correlation between MG type and stage of thymoma.
A distinct finding in causes of death was frequent deaths due to extrathymic malignancies in the thymomatous patients, in contrast to the nonthymomatous patients. In our previous article [11], we reported a higher incidence of extrathymic malignancies in patients with thymomatous MG (9 of 102 patients, 8.8%) than the expected incidence in the normal population (2.6%), calculated by the person-years method. Papatestas [12] reported that 29 extrathymic malignancies occurred in 246 patients with thymomatous MG (11.7%). Thymoma might enhance occurrence of extrathymic malignancies.
In present report, RRs were about 30%, and PRs were about 80% in the thymomatous patients. These results were inferior to those in patients with nonthymomatous MG. Such a finding is common in many articles dealing with this theme [2, 9, 13, 14]. The reason for it is yet unclear.
The RR of the thymoma series by Papatestas and colleagues [14] (174 patients) was 10.0%, and in the one by Maggi and co-workers [8] (162 patients) RR was 15.7% and PR was 76.0%. Evoli and associates' series (84 patients) [9] showed a PR of 64%. The results of our series are superior to these.
Previously, we compared the results of simple thymectomy and extended thymectomy in patients with thymomatous MG [15]. The RRs of the patients with thymomatous MG treated by simple thymectomy were 13% at 1 year, 6% at 3 years, and 11% at 5 years. On the other hand, the RRs of those treated by extended thymectomy were 27% at 1 year, 30% at 3 years, and 26% at 5 years. The PRs were 56% at 1 year, 56% at 3 years, 56% at 5 years in the simple thymectomy group and 81% at 1 year, 74% at 3 years, and 84% at 5 years in the extended thymectomy group.
Papatestas and associates [14] performed transcervical thymectomy in 44 patients and transthoracic thymectomy in 130 thymomatous patients. However, their transthoracic thymectomy was not intended to resect the extrathymic adipose tissues. As described above, Maggi and associates' series included both the patients treated by simple thymectomy and those treated by extended thymectomy [8]. In our series, we performed extended thymectomy in all patients. Accordingly, the superiority of our results is explained by the predominance of extended thymectomy. This finding suggests the importance of more extensive elimination of thymic tissue, also in thymomatous MG patients.
Many factors influencing the effects of thymectomy have been reported. Some were investigated in this study. As concerns age at the time of operation, duration of disease, and titer of acetylcholine receptor antibody, the patients were divided into two groups with even numbers.
With regard to age at the time of operation in the nonthymomatous patients, the younger group (34 years or less) showed better results than those of the older group (35 years or more). Such a finding is consistent with other reports. However, our previous article [3] reported that the results of the younger (49 years or less) and the older (50 years or more) patient groups did not differ. We suggest that such discordance is due to bias in the number of cases (119:27) and a short follow-up period. In the thymomatous patients, a similar tendency was observed, but it was not significant.
Duration of disease is an important prognostic factor. Our investigation showed superiority of the short-duration group in both the nonthymomatous and the thymomatous patients, coincident with our previous article [16].
The relationship of MG type and operative effect has been discussed frequently. Whether thymectomy is indicated for type I has been controversial. However, this long-term follow-up has shown no difference between three MG types (I, IIa, IIb) in the nonthymomatous group, and indicated also the effectiveness of extended thymectomy for type I disease. In the patients with thymomatous MG, thymectomy was most effective in type I, less in type IIa, and least in type IIb. These findings were quite contrary to those in the nonthymomatous patients. Maggi and associates [8] reported 23.7% of RR in type I and IIa, and 11% in type IIb and III. Patients with thymomatous MG that was less severe could gain better benefits from thymectomy. However, the reason for such findings is not clear.
Our previous report [17] concerning the titer of acetylcholine receptor antibody showed that a decrease in the postoperative titer correlates with the effect of thymectomy, but the preoperative titer cannot be used to predict the effect. Also, the present investigation did not demonstrate a relationship between the preoperative titer of acetylcholine receptor and the effect of the operation in the nonthymomatous and the thymomatous group.
The association of thymectomy and steroid therapy is still controversial. Some investigators recommend routine steroid therapy before thymectomy [18]. In this report, follow-up results of the groups with and without preoperative steroid therapy were compared. Although the numbers of both groups were different, background characteristics were nearly even. There were no distinctive differences between the results of both groups. Steroids may produce various side effects and delay of therapeutic period due to difficulty of withdrawal. Even without steroid administration, in our experience early postoperative management is usually not difficult. It is our practice to avoid preoperative steroid therapy.
There was no difference in RRs between three stage groups of thymoma. Our previous article reported higher RRs in stage I and II patients than in stage III and IV patients [19]. Although RRs in stage I and II patients were similar in the previous and the present study, the RRs in stage III patients increased from 11% to 20% at 1 year, from 7% to 33% at 3 years, from 8% to 20% at 5 years, and from 25% to 35% at 10 years. Such differences may be caused by the fact that the stage III patients in this report are limited to the ones who had undergone extended thymectomies.
To overcome the limits of the effects of the extended thymectomy, Jaretzki and colleagues [20] have advocated "maximal thymectomy," meaning additional resection of fatty tissues in the cervical and hilar regions through a T-shaped cervical/sternal incision. Our investigation of hilar and posterior mediastinal fatty tissues in autopsied cases revealed thymic tissue histologically in only 7.7% of the cases [21]. The results of Jaretzki and colleagues [22] show a 46% RR and a 94% PR in 72 cases of MG without thymoma. The results do not exceed ours. Therefore, we do not favor enlargement of the extent of adipose resection beyond extended thymectomy.
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Acknowledgments |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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