Asian Cardiovasc Thorac Ann 2003;11:299-303
© 2003 Asia Publishing EXchange Ltd
Thymectomy for Myasthenia Gravis: 12-Year Experience
Rana S Singh, MCh,
Sukanta K Behera, MCh,
Saji Radhakrishnan, MCh,
Rajinder S Dhaliwal, MCh
Department of Cardiothoracic and Vascular Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
For reprint information contact: Rana S Singh, MCh Tel: 91 172 747 585 Fax: 91 172 744 401 email: medinst{at}pgi.chd.nic.in Department of Cardiothoracic and Vascular Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India.
 |
ABSTRACT
|
|---|
Thymectomy has been shown to be effective in the treatment of myasthenia gravis. The logical goal of operation is the complete removal of the thymus, but there is no consensus on the selection criteria of patients for surgery and the choice of surgical approach. We retrospectively reviewed 56 patients with myasthenia gravis who had been treated surgically by transsternal radical thymectomy between January 1990 and March 2002. The patients were symptomatically grouped according to the modified Osserman clinical classification. There was 1 hospital death, and 53 patients had been followed up for between 1 month and 12 years. Improvement after thymectomy was observed in 1 of 4 patients (25%) in Osserman group I, 25 of 34 patients (74%) in Osserman group IIA, and 16 of 18 patients (89%) in combined Osserman groups IIB and IIC. Transsternal radical thymectomy is an effective therapy for myasthenia gravis. Sustained improvement is achievable in female patients with moderate to severe symptoms and in patients with thymic hyperplasia.
|
INTRODUCTION
|
|---|
Myasthenia gravis (MG) is an autoimmune disorder directed against postsynaptic acetylcholine receptors, causing weakness and easy fatigability of voluntary muscles. Untreated, there is a 40% mortality rate in 10 years.1 Surgical removal of the thymus has become an accepted and practiced therapeutic option worldwide for MG since Blalock and colleagues2 first performed this operation in 1936 and described their technique in 1939. Patients with MG who underwent thymectomy showed greater improvement with respect to symptoms and medication requirements than patients treated nonsurgically.3 Thymectomy is recognized as an effective therapy complementing the medical management of these patients. Controversy persists, however, over the selection of patients for surgery and the optimal surgical approach. The use of the transcervical route for thymectomy was initially encouraged because of lower morbidity and mortality compared to the transsternal approach. However, the latter offers better access to the mediastinum and makes extended excision of the gland possible. Considering that these advantages have been reported to lead to better long-term results, thereby offsetting the drawback of greater surgical stress imposed on patients, many experts prefer transsternal thymectomy.4,5
This report reviews our experience with thymectomy for MG using the transsternal approach. A variety of preoperative clinical variables are assessed to determine if patient selection could have an effect on the long-term clinical results of this approach.
|
PATIENTS AND METHODS
|
|---|
Between January 1, 1990, and March 31, 2002, 56 patients underwent thymectomy for MG. The medical records of these patients were reviewed retrospectively by a single reviewer. No patient who had thymectomy for MG during this period was excluded from the study.
All patients were examined and referred for operation by the Neurology department after investigations. Thymectomy was recommended in patients who had a thymoma, had generalized symptoms of MG with a life expectancy of at least 10 years, or had ocular symptoms refractory to medical management. A consistent protocol of perioperative care was used, encompassing preoperative preparation, anesthetic and operative techniques, and postoperative medical and nursing care.
The diagnosis was established on the basis of typical findings on neurological examinations and a positive prostigmin test. In all patients, confirmatory evidence was provided by a decremental response on repetitive nerve stimulation and an abnormal response on single-fiber electromyography. Diagnosis was further supported by elevated acetylcholine receptor antibody titers. Most patients also had computed tomography (CT) done. Thymic hyperplasia was suggested by a diffuse enlargement of the thymus on the CT scan, while a mass in the thymus may suggest a thymoma and early thymectomy is indicated. However, the cases considered inoperable because of extensive involvement of neighboring structures or because of pericardial or pleural dissemination were not taken up for surgery. All patients were evaluated preoperatively with spirometry and chest radiography.
Preoperative medications included anticholinesterase drugs and steroids, which were continued until the time of surgery and readministered immediately after surgery at regular intervals. Plasma exchange was done only in selected patients. Patients receiving steroids at the time of the operation was given a perioperative stress dose, after which they were weaned off the drugs. The use of neuromuscular blockers during anesthesia was avoided. Sedative drugs and drugs precipitating myasthenic crisis were strictly avoided in the postoperative period.
The operative technique was similar in all patients. The thymus was approached through a full median sternotomy or, in a few patients, through an upper partial mid-sternotomy (
incision) for cosmetic reasons. Dissection was performed bluntly from the pericardium and the pleura. The adipose tissues around the upper poles of the thymus, around both brachiocephalic veins, and on the pericardium were resected meticulously. If necessary, the pleural cavity was entered. The borders of resection were the diaphragm caudally, the thyroid gland cranially, and the phrenic nerves laterally. Postoperative radiation treatment was used for grossly invasive tumors where the resection margins were considered to be inadequate based on intraoperative evaluation (Masaoka stage II or III thymomas).
The patients were evaluated every 3 months after thymectomy. Follow-up data were available for 53 patients over a mean period of 40 months (range, 1 month to 12 years).
The modified Osserman clinical classification6 (Table 1
) was used to define disease severity. Patients were classified postoperatively and at follow-up as in remission (asymptomatic, no medications needed), improved (lower Osserman group or same group on fewer medications), unchanged, or symptomatically worse. Statistical comparisons were done using the chi-squared test, and statistical significance is defined as p < 0.05.
|
RESULTS
|
|---|
Among the 56 patients with MG who underwent transsternal radical thymectomy, 36 were nonthymomatous and 20 thymomatous. In the nonthymomatous group, there were 20 females and 16 males, with a mean age of 25.9 years (range, 13 to 44 years). In the thymomatous group, there were 6 females and 14 males, with a mean age of 33.7 years (range, 19 to 60 years).
The preoperative duration of the disease ranged from 2 months to 5 years (mean, 19.5 months) in the nonthymomatous group and from 3 months to 4 years (mean, 16.8 months) in the thymomatous group. The severity of the disease, categorized by the modified Osserman system, is shown in Table 2. Preoperatively, 10 patients (28%) in the nonthymomatous group and 4 (20%) in the thymomatous group were on steroid treatment.
A full median sternotomy was used in 48 patients and an upper partial mid-sternotomy in 8. In the nonthymomatous group, the thymus and the mediastinal fat were resected from the diaphragm cephalad up to the cervical thymic extensions. Laterally, the margins of resection extended up to the phrenic nerves and included the mediastinal pleura. The phrenic nerves were not completely dissected. In the thymomatous group, complete radical excision was done in 15 patients. Another 2 patients had extensive infiltration of the surrounding tissues and only palliative resection could be done. The left phrenic nerve in another patient was sacrificed. The innominate vein was involved in the remaining 2 patients, and the tumor was shaved off the vein. Of the 20 patients in the thymomatous group, 10 had Masaoka stage I disease, 3 were in stage IIA, 5 in stage IIB, and 2 in stage III. No patients with suspected Masaoka stage IV disease had thymectomy.
Of the 56 patients, 45 (80%) were extubated in the operating room, 7 (13%) were extubated within 6 hours of surgery, and 3 (5%) were extubated on the 1st postoperative day. The remaining patient, who had acute fulminating MG (Osserman group IIC), was ventilated for 6 days before succumbing to respiratory insufficiency and sepsis. This patient did not receive steroids in the pre- or postoperative period. Postoperative complications occurred in 6 patients (11%) and included wound infection in 2 patients requiring dressing of the wound for a few days, pneumonia in 2 patients requiring antibiotic treatment for 2 weeks, and pneumothorax in 2 patients that resolved with drainage through an intercostal chest tube. Of these, 1 patient with wound infection and 1 with pneumonia were on steroid therapy pre- and postoperatively. The mean postoperative hospital stay was 7.2 days (range, 4 to 12 days).
The histology of the resected thymus glands consisted of thymic hyperplasia in 30 patients, atrophic thymus in 2, normal thymus in 4, and thymoma in 20 (10 were invasive and another 10 noninvasive). Histologic classification of thymomas was based on Lewis and associates’ modification7 of the Lattes-Bernatz classification.
In the nonthymomatous group, the 30 patients (54% of the series) with thymic hyperplasia showed a response rate of 73% (22 patients), which was significantly better than a 33% response rate (2 patients) seen in the 6 patients (11% of the series) with normal or atrophic thymus (p < 0.05). Comparison of histology with preoperative Osserman classification revealed no statistically significant relationship. In the thymomatous group, 11 patients (55%) improved postoperatively, a response rate that was similar to that of the series as a whole (63% or 35 patients). There was no correlation in the thymomatous group between thymoma invasiveness and the response.
The relationship between preoperative Osserman classification and late clinical outcome based on the last follow-up is illustrated in Figure 1. Of the 18 patients (32% of the series) in preoperative Osserman groups IIB and IIC, 8 (44%) were in complete remission at the last follow-up and an additional 8 (44%) had improved. Of the 34 patients (61% of the series) in group IIA, 10 (29%) were in remission and 15 (44%) had improved. Of the 4 patients (7% of the series) in group I, only 1 (25%) had improved. Response to thymectomy improved significantly with the preoperative Osserman group level. Patients in groups IIA, IIB, and IIC responded significantly better to thymectomy than patients with ocular symptoms only (p < 0.01).
View larger version (26K):
[in this window]
[in a new window]
|
Figure 1. Preoperative severity of disease (categorized by Osserman groups) versus clinical response (in remission or improved) at follow-up after thymectomy.
|
|
Patients’ age, preoperative duration of symptoms, and postoperative length of follow-up did not correlate with response (in remission or improved) to thymectomy. Patients’ sex correlated with response, with 75% of female patients responding compared to only 45% of males (p < 0.05).
|
DISCUSSION
|
|---|
Disagreement over the use of thymectomy in patients with MG pertains to the selection of patients, the optimal surgical approach (transcervical versus transsternal), and the extent of resection necessary to achieve good therapeutic outcome. Comparisons between published series of patients are made difficult by differences in surgical philosophy and in patient selection.8,9 These difficulties are compounded by the lack of a standardized method for assessing patient status both before and after thymectomy. Our standard surgical approach involves a median sternotomy, either full or partial, and complete resection of the thymus including the cervical extensions. Partial sternotomy was decided, for cosmetic reasons, for 8 young female patients whose CT scans showed thymic hyperplasia. However, access to the diaphragm through this approach is not very satisfactory. The anterior mediastinal fat contains thymic remnants in 72% of patients, which can be thoroughly cleared only with a full transsternal approach.10 Nevertheless, Masaoka and colleagues10 found no difference in the postoperative results of thymectomy between the full and the partial sternotomy groups. We do not extensively dissect the phrenic nerves so as to avoid postoperative diaphragmatic palsy and respiratory compromise.
Transcervical thymectomy may result in incomplete resection. The rate of reoperation to excise unrelated thymic remnants following this approach has been reported to be as high as 27%.10 Cooper and colleagues9 described a transcervical approach to thymectomy using a sternal elevator that permits extensive resection. Their reported clinical results were comparable to those obtainable with transsternal thymectomy.8 The transcervical approach confers the potential advantage of a shorter hospital stay. However, it is difficult to objectively compare the 2 surgical techniques in the absence of a prospective randomized trial.
Our clinical experience encompasses the entire spectrum of MG from minor ocular involvement to acute life-threatening disease. All the patients were managed in a standardized fashion. Our results show that thymectomy in patients with MG can be performed safely with minimum morbidity and acceptable mortality. Pre- and postoperative steroid therapy did not have any significant effects on postoperative mortality and morbidity. Patients were routinely kept in the hospital for 5 to 10 days for observation for possible respiratory compromise. Plasmapheresis may be useful as adjuvant therapy in patients with impaired respiratory mechanics.11,12 Kas and associates13 reported serious complications in 22% of their patients with respiratory insufficiency. Our data reveal a postoperative complication rate of 11% with the majority of the patients (80%) being extubated in the operating room.
The value of various histologic classifications of thymomas is still controversial. Some authors do not pay any attention to the histologic type. Others view the presence of epithelial tumors as an adverse prognostic factor because of the high frequency of invasive tumors in this histologic type. According to Regnard and colleagues,14 prognosis could be better evaluated by intraoperative identification and evaluation (of the extent of the tumor and the possibility of complete resection) than by histologic analysis. Quintanilla-Martinez and associates15 found Marino and Müller-Hermelink’s histologic classification to be an independent prognostic factor. However, in the same study, the Masaoka clinical stage was the best prognostic factor, more significant than the histologic classification. MG is often reported in association with predominantly lymphocytic tumors. However, we found in our study an even distribution of histologic subtypes in myasthenic patients with thymomas.
The results of the present study indicate that patients with thymic hyperplasia responded better than those with normal or atrophic thymus and that female patients can expect significantly better results from thymectomy than males. Similar results have been reported in the literature.16,17 Patients with more severe symptoms of MG clearly benefit from thymectomy, which should be performed early in the course of the disease in this group of patients, with concomitant medical therapy that is optimized perioperatively to minimize operative morbidity. Our patients with ocular MG (Osserman group I) demonstrated significantly lower response rates than those with more severe disease. The response rate of 25% in this small group of patients is similar to the rate of spontaneous improvement expected during the natural course of the disease.18
The results of extensive thymectomy through the transsternal approach, as performed in all of our patients, compare favorably with published results using either transcervical thymectomy or radical (maximal) thymectomy.9,19,20 The morbidity and mortality rates were low and there was little need for postoperative ventilatory support. The improvement in the vast majority of patients suggests that adequate thymic tissue is removed with this operation. Best results are to be expected in female patients with moderate to severe symptoms and in patients with thymic hyperplasia. Patients with ocular symptoms should only be managed medically, as the majority of these patients in our study did not improve with thymectomy.
|
REFERENCES
|
|---|
- Buckingham JM, Howard FM Jr, Bernatz PE, Payne WS, Harrison EG Jr, O’Brien PC, et al. The value of thymectomy in myasthenia gravis: a computer-assisted matched study. Ann Surg
1976;184:453–8.[Medline]
- Blalock A, Mason MF, Morgan HJ, Riven S. Myasthenia gravis and tumors of the thymic region. Report of a case in which the tumor was removed. Ann Surg
1939;110:544–61.[Medline]
- Perlo VP, Poskanzer DC, Schwab RS, Viets HR, Osserman KE, Genkins G. Myasthenia gravis: evaluation of treatment in 1,355 patients. Neurology
1966;16:431–9.[Free Full Text]
- Bulkley GB, Bass KN, Stephenson GR, Diener-West M, George S, Reilly PA, et al. Extended cervicomediastinal thymectomy in the integrated management of myasthenia gravis. Ann Surg
1997;226:324–34.[Medline]
- Masaoka A, Yamakawa Y, Niwa H, Fukai I, Kondo S, Kobayashi M, et al. Extended thymectomy for myasthenia gravis patients: a 20-year review. Ann Thorac Surg
1996;62:853–9.[Abstract/Free Full Text]
- Sabiston DC, Spencer FC, editors. Surgery of the chest. 6th ed. Vol. 2. Philadelphia: Saunders, 1995:1100–22.
- Lewis JE, Wick MR, Scheithauer BW, Bernatz PE, Taylor WF. Thymoma. A clinicopathologic review. Cancer
1987;60:2727–43.[Medline]
- Jaretzki A III, Penn AS, Younger DS, Wolff M, Olarte MR, Lovelace RE, et al. "Maximal" thymectomy for myasthenia gravis. Results. J Thorac Cardiovasc Surg
1988;95:747–57.[Abstract]
- Cooper JD, Al-Jilaihawa AN, Pearson FG, Humphrey JG, Humphrey HE. An improved technique to facilitate transcervical thymectomy for myasthenia gravis. Ann Thorac Surg
1988;45:242–7.[Abstract]
- Masaoka A, Nagaoka Y, Kotake Y. Distribution of thymic tissue at the anterior mediastinum. Current procedures in thymectomy. J Thorac Cardiovasc Surg
1975;70:747–54.[Abstract]
- d’Empaire G, Hoaglin DC, Perlo VP, Pontoppidan H. Effect of prethymectomy plasma exchange on postoperative respiratory function in myasthenia gravis. J Thorac Cardiovasc Surg
1985;89:592–6.[Abstract]
- Hatton PD, Diehl JT, Daly BD, Rheinlander HF, Johnson H, Schrader JB, et al. Transsternal radical thymectomy for myasthenia gravis: a 15-year review. Ann Thorac Surg
1989;47:838–40.[Abstract]
- Kas J, Kiss D, Simon V, Svastics E, Major L, Szobor A. Decade-long experience with surgical therapy of myasthenia gravis: early complications of 324 transsternal thymectomies. Ann Thorac Surg
2001;72:1691–7.[Abstract/Free Full Text]
- Regnard JF, Magdeleinat P, Dromer C, Dulmet E, de Montpreville V, Levi JF, et al. Prognostic factors and long-term results after thymoma resection: a series of 307 patients. J Thorac Cardiovasc Surg
1996;112:376–84.[Abstract/Free Full Text]
- Quintanilla-Martinez L, Wilkins EW Jr, Choi N, Efird J, Hug E, Harris NL. Thymoma. Histologic subclassification is an independent prognostic factor. Cancer
1994;74:606–17.[Medline]
- Rubin JW, Ellison RG, Moore HV, Pai GP. Factors affecting response to thymectomy for myasthenia gravis. J Thorac Cardiovasc Surg
1981;82:720–8.[Medline]
- Mulder DG, Herrmann C Jr, Keesey J, Edwards H. Thymectomy for myasthenia gravis. Am J Surg
1983;146:61–6.[Medline]
- Grob D, Arsura EL, Brunner NG, Namba T. The course of myasthenia gravis and therapies affecting outcome. Ann N Y Acad Sci
1987;505:472–99.[Medline]
- DeFilippi VJ, Richman DP, Ferguson MK. Transcervical thymectomy for myasthenia gravis. Ann Thorac Surg
1994;57:194–7.[Abstract]
- Jaretzki A III, Wolff M. "Maximal" thymectomy for myasthenia gravis. Surgical anatomy and operative technique. J Thorac Cardiovasc Surg
1988;96:711–6.[Abstract]
TOP
ABSTRACT
INTRODUCTION
