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ORIGINAL CONTRIBUTION |
Thoracic Surgery Unit, Department of Surgery, King Khalid University Hospital, King Saud University, Riyadh, Kingdom of Saudi Arabia
For reprint information contact: Mahmoud Ashour, FRCS Tel: 966 1 467 1575 Fax: 966 1 467 9493 email: mashour90{at}hotmail.com Thoracic Surgery Division, Department of Surgery (37), King Khalid University Hospital, College of Medicine, P.O. Box 7805, Riyadh 11472, Kingdom of Saudi Arabia.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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PATIENTS AND METHODS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Maximal thymectomy was performed utilizing a transcervical-transsternal approach according to the technique described by Jaretzki and Wolff.2 Both the neck and mediastinal pools of the gland were removed enblock with the surrounding tissue, including the fatty tissue anterior and anterolateral to the trachea from below the thyroid gland to the superior mediastinum. In the mediastinum, excision included thymic gland and fatty tissue extending down to the diaphragm inferiorly, and between the two phrenic nerves laterally. Also included was cardiophrenic fatty tissue, retroinnominate and aorto pulmonary window areas. In all cases, staff pathologists examined specimens which were sent separately from various locations. All patients were routinely extubated at the end of the procedure, nursed overnight in the Intensive Care Unit and initially restarted on half their preoperative medication doses. This was altered during hospitalization according to the clinical status.
Complete follow-up was available for a mean period of 91.1 months (range, 8 to 180 months), with patients evaluated at 6 monthly intervals. At the last known point of follow-up, patients were considered in "complete remission" if they were asymptomatic on no medication, and "improved" if they were having no or less symptoms on less or the same preoperative medication. Failure of surgical treatment was noted if they were still on their preoperative doses with no improvement in symptoms.
Patient preoperative data was initially set against outcome, with the latter frequently dichotomized to "remission" versus "no improvement" or "benefit" versus "no improvement." Analysis was performed using x 2 and Fisher’s exact test in contingency tables. Univariate analysis was then performed on all patient factors listed in Table 1
. A p value of less than 0.05 was considered significant. Data was analyzed using the StatPac Gold Statistical Analysis Package (version 3.2).
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RESULTS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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details the preoperative factors and associations with outcome. There were 100 patients (63 female and 37 male) with a median age of 25 years (range, 4 to 61 years). The duration of the disease ranged between one month to 20 years (mean 26 months). Anti Ach R antibody test was performed in 90 patients with a positive result in 48. Preoperatively, seven patients were diagnosed to have thymoma. According to the Osserman classification, seven patients were in class I (ocular), 31 in class II (mild generalized weakness), 47 in class III (moderate generalized weakness), and 15 in class IV (severe generalized weakness). Steroids were tapered to nil in 30 patients (30 of 40 patients on large steroid doses) and reduced in the remaining 10. Preoperative plasmapheresis was performed in patients with generalized symptoms (82 out of 100 patients), with a mean of three sessions. Seven patients with ocular MG were excluded and 11 patients declined the plasmapheresis. There was no operative mortality and 4 patients (4%) developed postoperative complications: one patient was re-explored for bleeding, one was re-explored to drain a pericardial effusion secondary to central line leak and two developed septicemia.
Histological examination revealed: thymic hyperplasia in 76 cases; atrophy in 9; normal thymus in 8; and thymoma in 7. The incidence of ectopic thymus was 27% (27 of 100). All patients completed follow-up with a mean period of 7.6 years (range, 8 to 180 months). In non-thymomatous MG patients (93 cases), complete remission was achieved in 36 cases (38.7%) at the last known point of follow-up, while in thymomatous MG (7 cases), no cases had complete remission. Improvement of non-thymomatous MG patients was 47.3% (45 of 93) with a total benefit rate of 86%. Fourteen percent (13 of 93) did not improve. Conversely, in the thymomatous group, improvement was 28.6% (2 of 7) and no improvement in 71.4% (5 of 7). For the non thymomatous MG patients, the number of patients at each evaluation, the complete remission rates (CR) and the total benefit rates (the sum of remission and improvement rates), are shown in Table 2 and Figure 1.
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Univariate analysis (p < 0.05) of factors influencing outcome of surgery included: age, sex, duration of the disease, Osserman classification, preoperative steroid therapy, Anti Ach R antibodies, histopathology and ectopic thymic tissue (Table 1). Patients below the age of 50 years had better outcome than those over 50 (p = 0.0044). Furthermore, the presence of thymoma was associated with poor outcome (p = 0.00003). Patients with evidence of ectopic thymic tissue also had a significantly poorer outcome in comparison to other patients without ectopic thymic tissue (p = 0.0001).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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). A similar experience was reported previously by Jaretzki et al.4 This study has indicated as well that the total benefit rate increased continously with time (Figure 1), an observation that was also reported by Durelli et al.5 Furthermore, other thymectomy techniques including transcervical or transternal were associated with similar outcome during a follow-up period of 5 to 8 years, as reported in other studies to be 39.7%,6 44.2%,7 and 45.8%.8 Ectopic thymic tissue has been located in various sites outside the visible thymus.2,9 27 patients out of 100 in this study showed the presence of ectopic thymic tissue. In our previous study ectopic thymic tissue was found in 39.5% of patients.10 The impact of ectopic thymic tissue on complete remission rate was found to be statisticaly significant as a poor prognostic factor (p = 0.0001). Only five patients out of 27 (18.5%) with ectopic thymic tissue achieved complete remission contrary to 31 out of 73 patients (42.5%) without ectopic thymic tissue. A similar finding was reported previously.10
We found that age at onset of the disease and thymic histology were significant prognostic factors. Age at the time of thymectomy has shown a strong correlation with outcome. In this study we found 86% improvement in those < 50 years versus 37% in those > 50 years. A similar experience was reported by Masaoka et al.8 Thymic histology is also a relatively consistent predictor of response. Hyperplasia correlates in some studies with an increase in improvement rates.11 We detected a significantly increased proportion of improved patients with hyperplastic thymus versus other types of histology. In this study 32 out of 76 patients (42%) with hyperplastic thymus achieved complete remission while none of the patients with thymoma (7 patients) achieved complete remission. A similar finding was reported by others.8,12 We also found that patients with thymoma were significantly more prone to experience deterioration in their clinical course.
Sex is a factor that shows disparate associations among studies. Some studies have found improved outcome in female patients,13 whereas others have found increased improvement in male patients,14 or no sex predictor value.4,15 However, in this study, the total benefit rate was estimated to be 85% in female patients versus 75% in male patients. This result was not considered to be statistically significant.
The duration of the disease was not found to have a significant relation to complete remission in our series, contrary to the findings of many other studies.13 Twenty out of 55 patients (36%) with disease duration of less than one year had complete remission while 16 out of 45 (35.5%) patients with disease duration of more than one year achieved complete remission.
Kagotani highlighted the importance of Anti Ach R antibodies both as a prognostic factor and in determining the course of future therapy after thymectomy.16 We did not find any significant difference in the complete remission rate based on the presence or absence of Anti Ach R antibodies. Fifteen out of 48 patients (31%) with positive antibodies achieved complete remission, compared to 16 out of 42 (38%) with negative antibodies.
A poor complete remission rate among patients who required steroid therapy prior to surgery may reflect a more severe form of the disease in these patients.4 In this study, out of 40 patients managed with steroids, 11 (27%) had complete remission, while 25 out of 60 patients (40%) who were not on steroid therapy had complete remission. This result, although not statistically significant, emphasizes the importance of a steroid sparing effect of thymectomy. The average daily dose of steroids was reduced from 54 mg prednisolone preoperatively to an average of 12 mg prednisolone postoperatively.
While the role of surgery in generalized MG is widely accepted, this study has shown the Osserman classification not to be a significant predictor (Table 1). Furthermore, controversy remains concerning the role of thymectomy in pure ocular MG.4,16 In this series, 7 patients with ocular MG were operated on. Two of these seven patients (28.5%) achieved complete remission and the other three improved (43%). In a similar study by Schumm a complete remission rate was achieved in 16.7% only.17
In this series, there was no mortality and morbidity occurred in 4% of patients only. Two patients developed septicemia, and the other two were re-explored for bleeding. For one of them, bleeding occurred as a result of central line injury. No phrenic or recurrent nerve injuries were encountered in this series contrary to other studies which reported an incidence of 4%.18
In light of the above, we conclude that maximal thymectomy is an effective and safe procedure for treatment of myasthenia gravis. This study has also shown that the complete remission and the total benefit rates are prone to increase over time. Moreover, age, thymic histology and ectopic thymic tissue are significant prognostic factors for the outcome of thymectomy.
Presented at the 10th Annual Meeting of European Society of Thoracic Surgeons, 26–28 October 2002, Istanbul, Turkey.
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This article has been cited by other articles:
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  C. Prokakis, E. Koletsis, S. Salakou, E. Apostolakis, N. Baltayiannis, A. Chatzimichalis, T. Papapetropoulos, and D. Dougenis Modified maximal thymectomy for myasthenia gravis: effect of maximal resection on late neurologic outcome and predictors of disease remission. Ann. Thorac. Surg., November 1, 2009; 88(5): 1638 - 1645. [Abstract] [Full Text] [PDF]
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 H. El-Bawab, W. Hajjar, M. Rafay, A. Bamousa, A. Khalil, and K. Al-Kattan Plasmapheresis before thymectomy in myasthenia gravis: routine versus selective protocols Eur. J. Cardiothorac. Surg., March 1, 2009; 35(3): 392 - 397. [Abstract] [Full Text] [PDF]
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J. M. Ponseti, J. Gamez, R. Vilallonga, C. Ruiz, J. Azem, M. Lopez-Cano, and M. Armengol Influence of ectopic thymic tissue on clinical outcome following extended thymectomy in generalized seropositive nonthymomatous myasthenia gravis Eur. J. Cardiothorac. Surg., November 1, 2008; 34(5): 1062 - 1067. [Abstract] [Full Text] [PDF]
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H. El-Bawab, A. A. Al-Sugair, M. Rafay, W. Hajjar, M. Mahdy, and K. Al-Kattan Role of flourine-18 fluorodeoxyglucose positron emission tomography in thymic pathology Eur. J. Cardiothorac. Surg., April 1, 2007; 31(4): 731 - 736. [Abstract] [Full Text] [PDF]
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J. W. Rubin Invited commentary. Ann. Thorac. Surg., September 1, 2006; 82(3): 1007 - 1008. [Full Text] [PDF]
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