Asian Cardiovasc Thorac Ann 2007;15:371-375
© 2007 Asia Publishing EXchange Ltd
Thymectomy for Myasthenia Gravis: Prognostic Factors in 70 Patients
Manucher Aghajanzadeh, MD,
Hossein Khoshrang, MD1,
Ali Mohammadzadeh, MD1,
Seyed A Roudbari, MD2,
Amir R Ghayeghran, MD2
Department of Thoracic Surgery
1 Department of Anesthesiology
2 Department of Neurology, Razi and Poorsina Teaching Hospital, Guilan University of Medical Sciences, Rasht, Iran
For reprint information contact: Manucher Aghajanzadeh, MD, Tel: 98 131 772 2389, Fax: 98 131 772 2389, Email: maghajanzadeh2003{at}yahoo.com, 37 Yalda Building, 100 Street, Golsar Avenue, Rasht, Iran.
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ABSTRACT
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Thymectomy has become increasingly accepted as an efficacious procedure for myasthenia gravis, with high rates of complete clinical remission. Predictors of the response to thymectomy for myasthenia gravis vary in the literature. We retrospectively reviewed the clinical records of 70 patients (63% female; mean age, 38 years) diagnosed with myasthenia gravis from August 1993 to August 2004, to determine the factors predicting outcome. Complications occurred in 20%, but there was no hospital mortality. Complete clinical remission was obtained postoperatively in 47%. Our results indicate that patients with less than 1 year’s duration of disease have a better prognosis, and Osserman stages I, IIa, and IIb are also associated with higher clinical remission rates. Female patients have a better prognosis than males, and the younger the patient the better the outcome. Thymectomy is indicated for myasthenia gravis as early as possible in the course of the disease.
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INTRODUCTION
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Myasthenia gravis (MG) is an autoimmune disorder resulting from the binding of antibodies to acetylcholine receptors, which gives rise to weakness and fatigue of the voluntary musculature. It is the most common primary disorder of neuromuscular transmission. Myasthenia gravis is usually caused by an acquired immunologic abnormality. Diagnostic methods include the Tensilon test, acetylcholine receptor antibody levels, single-fiber electromyography, and repetitive nerve stimulation. Medical treatment with anticholinesterase agents, immunosuppressive drugs, plasmapheresis, steroids, and gamma globulin results in complete clinical remission in only 15% of patients.1 In 1941, Blalock and colleagues2 reported the surgical management of MG by thymectomy in 6 patients. Since then, thymectomy has become an increasingly accepted procedure for treatment of MG, with complete remission in up to 80% of patients.3 The rate of complete remission in Iranian patients undergoing thymectomies has not been reported. The current indications for thymectomy for MG include early generalized moderate to severe disease stabilized with medication, and resistant ocular MG.3–5 In this retrospective study, we assessed the early and long-term results of thymectomy for MG in 70 patients, to determine the major prognostic factors influencing the outcome after thymectomy.
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PATIENTS AND METHODS
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We studied the clinical records of 70 confirmed cases of MG in Razi Teaching Hospital and Aria Private Hospital, Rasht, Iran, from August 1993 to August 2004. All patients were referred by neurologists and underwent thymectomy by a thoracic surgeon. The Osserman classification was used for MG staging.6 Clinical stages were: grade I, ocular involvement; grade IIa, mild generalized ocular myasthenia; grade IIb, moderate generalized myasthenia involving bulbar musculature; grade III, acute fulminant form; and grade IV, severe late myasthenia. Follow-up periods ranged between 18 and 60 months. Preoperative stabilization before thymectomy included anticholinesterase, steroids, plasmapheresis, and immunoglobulin. Information on vital status and patient demographics was extracted from the medical files. All patients were regularly monitored in hospital and in our postoperative clinic. The variables studied were the time of diagnosis, clinical presentation, type of surgery, immediate and late complications, mortality and improvement.
An extensive transcervical incision was the surgical approach in 20 (28%) patients, a transcervical incision and partial sternotomy were performed in 40 (58%), and a median sternotomy in 10 (14%). In all cases, thymectomy was followed by removal of neighboring fat tissues and complete thymus excision through an extracapsular approach. Measurements of thymectomy outcomes were performed according to the criteria of Venuta and colleagues:7 complete clinical remission, significant clinical improvement with medication, moderate clinical improvement with medication, unchanged stable clinical status, and worse clinical status. Prognostic factors potentially influencing complete clinical remission after thymectomy were sex, age, clinical status according to the Osserman classification, time between diagnosis and operation, surgical approach, and pathologic findings from thymus examination postoperatively.
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RESULTS
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Patients’ ages ranged from 16 to 60 years (mean, 38 years); 43 (61%) were < 40 years old and 27 (39%) were > 40 years old. Forty four (63%) patients were women. The distribution according to Osserman classification is given in Table 1
. Duration of symptoms was < 12 months in 40 patients and > 12 months in 30. Postoperative pathology showed hyperplasia in 45 (64%) patients, thymoma in 23 (33%), and a normal thymus in 2 (3%). Postoperative morbidity and mortality are shown in Table 2. Seven patients with severe MG crisis attributable to respiratory infection were intubated and treated with prednisolone, plasmapheresis, and anticholinesterase agents. There was no hospital mortality. Three patients died during follow-up, all of the deaths were attributed to MG crisis, and all occurred in patients in Osserman stage IV; one of these 3 patients had an invasive thymoma. The deaths occurred 18, 24 and 48 months after thymectomy. The mean length of hospital stay was 15 days. Thirty four (49%) patients were extubated in the operating room and 18 (26%) remained intubated for 3 days in the intensive care unit. Eight (11%) patients were intubated for 7 days in the intensive care unit, and 10 (14%) remained intubated for 8 to 15 days. Ten (14%) patients needed a tracheotomy.
According to the outcome criteria, 32 (46%) patients had complete clinical remission, 22 (31%) had significant clinical improvement, 10 (14%) had moderate clinical improvement, 6 (9%) were unchanged, and 2 (3%) had a worse clinical status after 48 months. Younger patients were more likely to achieve complete clinical remission. Table 3 shows the difference in outcome criteria according to age. Table 4 shows outcome criteria according to sex. Preoperative treatment (plasmapheresis, steroids, immunoglobulin) did not correlate with complete clinical remission. There was no significant difference in outcome criteria according to surgical procedure. Patients in Osserman stages I, IIa, and IIb had a significantly better prognosis than those in other stages (Table 5). Complete clinical remission was attained in 42 patients with duration of disease < 1 year. Table 6 shows outcome criteria according to the pathologic findings in the resected thymus. There were no significant differences in outcome criteria according to pathologic findings.
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DISCUSSION
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The transcervical route was used originally for thymectomy.2 Other approaches include an upper sternotomy, median sternotomy, transsternal sternotomy, and a T-sternotomy incision.4–8 We used a transcervical partial sternotomy and a median sternotomy for thymectomies in our patients. Surgical treatment has become an increasingly accepted procedure, resulting in complete clinical remission in up to 42% of patients, and clinical improvement in up to 94%.6 In our series, 47% had complete clinical remission at 60 months and 32% had a significant clinical improvement. Several explanations for the mechanisms through which thymectomy influences MG outcome have been proposed. As the gland is known to contain certain muscular cells exhibiting acetylcholine receptors on their surface, the thymus is thought to contribute to acetylcholine receptor antibody production.1 On the other hand, it has also been noted that abnormal amounts of cells are produced in the thymus, with a subsequent T4/T8 fraction increment in MG patients; furthermore, these patients characteristically exhibit increased levels of thymopoietin.8–10
The degree of surgical resection is another issue of debate regarding thymectomy for MG. Many reports have advocated total or maximal thymectomy as the optimal surgical therapy.11,12 However, the Myasthenia Gravis Foundation of America Task Force has recently deemed the issue of fullness of resection to be unresolved.13 In an earlier series of MG patients, the transcervical approach for thymectomy was advocated because it resulted in fewer postoperative complications and a lower mortality rate compared with the transsternal approach.6 However, Blalock and colleagues2 had a higher complete clinical remission rate with the transsternal approach, presumably because of removal of fat tissue surrounding the thymus, which can be more easily performed by this approach. Bril and colleagues14 reviewed the long-term results in 52 patients who had undergone a transcervical thymectomy; complete remission occurred in 44.2% of their patients. An extended transsternal thymectomy gave 51% complete clinical remission in one report, and 80% of patients showed improvement.15 Another report noted complete clinical remission in 36% of patients, and 80% benefited from thymectomy.1 Complete clinical remission in patients operated on by a T-incision was 21% after thymectomy.5 The important prognostic role of the technique is now fully recognized. With this controversy, the surgical approach for thymectomy in non-thymoma MG does not influence the outcome of patients with MG.5,6 We used a T-incision (collar and partial sternotomy) in 40 (58%) patients.
A numbers of factors influencing the success of thymectomy for MG have been reported. Female patients and those younger than 40 years have been found to have higher rates of complete clinical remission.1 Age at the time of thymectomy has shown a strong correlation with outcome.16,17 Our study found a similar trend; 96% of young patients below 40 years improved after thymectomy. Many studies have found a better outcome in female patients, whereas others found more improvement in males, or no sex predilection.1,17,18 We found a significantly increased rate of improvement in females (75% vs 58% in males). Thymic pathology is also a predictor of response. Hyperplasia correlated with an increased rate of improvement in many studies, but the presence of thymoma has often been found to correlate with a poor response to thymectomy.9,10,14,16–18 We found that patients with thymoma (Masaoka stage I, II) had the same response rate as those with non-thymoma MG (52% vs 42%). Patients with invasive thymoma and epithelial thymoma have been reported to achieve the lowest complete clinical remission and survival rates.9,16 A better outcome after thymectomy for MG in Osserman class I and IIa has been reported.6,7 We also found more complete clinical remission in stage I and IIa patients (complete clinical remission in 4 of 5 and 15 of 34, respectively). Duration of MG presentation is a strong prognostic factor before thymectomy because it is said that the shorter the time from diagnosis to operation the better the outcome after thymectomy.19,20
The results of this study were compatible with previous reports, and we performed thymectomy for resistant ocular MG, as recommended by other authors.11,12,18 The findings indicate that time from diagnosis to operation < 12 months and Osserman stage I and IIa are the only strong positive prognostic factors that influence MG outcome after thymectomy. Sex, age, and pathology, seem to be not significantly associated with outcome, although females and younger patients are more likely to achieve complete clinical remission after thymectomy. We concluded that thymectomy is a beneficial procedure for MG patients, with a complete clinical remission rate of 45.7%, and all patients with MG greater than Osserman stage I or IIa or resistant ocular MG must be operated on in the early phase of the disease because this is strongly associated with an excellent outcome.
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ACKNOWLEDGMENTS
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We thank Dr. Manzar Hussein Akbar and Dr. Gilda Aghajanzadeh for the revision and final editing of this manuscript.
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REFERENCES
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ABSTRACT
INTRODUCTION
