Ann Thorac Surg 2006;81:305-308
© 2006 The Society of Thoracic Surgeons
Original article: General thoracic
Transsternal Thymectomy for Myasthenia Gravis: Surgical Outcome
Hassan Kattach, MRCS
a
,
Kyriakos Anastasiadis, MD
a
,
*
,
Julie Cleuziou, MD
a
,
Camilla Buckley, MRCP
c
,
Brian Shine, MRCP
b
,
Ravi Pillai, FRCS
a
,
Chandana Ratnatunga, FRCS
a
a Department of Cardiothoracic Surgery, John Radcliffe Hospital, Oxford, United Kingdom
b Department of Biochemistry, John Radcliffe Hospital, Oxford, United Kingdom
c Department of Clinical Neurology, Radcliffe Infirmary, Oxford, United Kingdom
Accepted for publication July 18, 2005.
* Address correspondence to Dr Anastasiadis, St Luke's Hospital, Panorama, 552 36, Thessaloniki, Greece (Email: anastasiadisk{at}hotmail.com).
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Abstract
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BACKGROUND: Transsternal thymectomy is well established in the treatment of myasthenia gravis. Surgical strategy and patient selection, however, remain controversial. This paper reports the experience of a supraregional center looking into the influence of different preoperative risk factors on surgical outcome.
METHODS: Between 1987 and 1998, 85 consecutive patients (65 female; mean age, 30.5 years) were enrolled. The mean preoperative Myasthenia Gravis Foundation of America stage was 2.3. The preoperative, early, and late follow-up data were analyzed retrospectively.
RESULTS: Mean follow-up was 4.5 years (range, 1 to 14; 376 follow-up years). Mean duration of disease before surgery was 31 months. There were no operative or late deaths. Eight patients had major complications. Seventy-two patients were free from any early or late morbidity. Immunosupression therapy patients were more prone to have complications. At their last visit, 15 patients (17%) were in complete remission; 67 reported clinical improvement. Sixty-three were asymptomatic or in stage I on no or minimal treatment. Remission and clinical improvement were not predicted by patient's age, sex, duration of disease prior to surgery, thymic pathology, or antiacetylcholine receptor antibodies titer. Greater severity of symptoms before surgery was associated with greater subsequent improvement. Remission at 1 year predicted remission at the end of follow-up.
CONCLUSIONS: Transsternal thymectomy for myasthenia gravis is safe and effective. It benefits most patients, especially those with severe symptoms. The long interval from diagnosis to surgery demonstrates it is never too late for thymectomy.
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Introduction
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Thymectomy for myasthenia gravis (MG) was first performed in 1936 by Blalock [1]. Since then, the removal of the gland has become established as a method of treatment of the disease. Today, even with the advancement in medical therapy, thymectomy remains an integral part of treatment of patient with severe forms of the disease [2]. Controversy, however, still exists about the indication and timing of surgery [3, 4]. The most appropriate surgical approach, moreover, is still under question [5–7]. Although a more aggressive approach may lead to better results, the incidence of major complications and postoperative morbidity is also increased. All these question whether the long-term results of thymectomy justify the potential morbidity of the procedure. The issue of the particular disease stage at which surgery is more beneficial also remains unresolved. We conducted our study to assess the effect of surgery on the course of the disease, as well as the influence of preoperative factors on surgical outcome.
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Patients and Methods
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From October 1987 to December 1998, 85 consecutive patients with MG underwent transsternal thymectomy in Oxford, a center that received local, national, and international referrals. Indications for surgery included generalized myasthenic symptoms resistant to medical treatment, refractory symptoms, and young patients. Sixty-five of the patients were female (76.5%). The mean age at surgery was 30.5 ± 13 years (range, 11 to 74). Table 1
demonstrates the preoperative data of the patients. Two patients had systemic lUpus Erythematous, a further 2 had thrombocytopenic purpura, and 1 had Crohn's disease.
The preoperative severity of the disease was classified according to the Myasthenia Gravis Foundation of America (MGFA) clinical classification (Table 2), whereas the postsurgical clinical status of the patient was assessed according to the MGFA postintervention status [8]. The mean preoperative MGFA class was 2.3 ± 0.6. Most patients were taking cholinesterase inhibitors preoperatively. Plasmapheresis and steroids were used in cases of severe symptoms to reduce the operative risk.
All patients had clinical follow-up by the same team of neurologists. Stable clinical outcome was also confirmed by telephoning the patients. The mean follow-up was 4.5 ± 3.4 years (range, 1 to 14). It represented 376 follow-up years.
An approval of Oxford Research Ethical Committee was obtained to perform the study.
Operative Technique
The operative technique remained constant during the study period. Three surgeons performed all thymectomies.
The transsternal thymectomy was performed through a full sternotomy. The perithymic fat of the anterior mediastinum was removed en bloc with the gland. The resection margins were the thyroid gland superiorly, the diaphragm inferiorly, and the phrenic nerves laterally. It did not involve the removal of every piece of tissue in the lateral wall of the mediastinal pleura, unless it has been invaded by a thymoma. The resection (previously described elsewhere [9]) was more extensive than standard transsternal thymectomy (T-3a), but less extensive than aggressive extended transsternal thymectomy (T-3b)(8). The cervical extensions of the gland were also removed. The patients were extubated as early as possible in the intensive care unit. Cholinesterase inhibitors were reintroduced on the second postoperative day in a dose than smaller the preoperative one.
All patients were clinically followed up by the same neurologist team.
Data and Statistics
The results are expressed as mean ± SD unless stated otherwise. The statistical analysis was performed using SPSS 10.0.5 statistical package (SPSS, Chicago, Illinois). The comparison between stages of MG was performed by a 
2 test. The sign test was used to assess the clinical improvement. Univariate and multivariate analyses were performed using a logistic regression model. A p value of 0.05 or less was considered to be significant.
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Results
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There was no significant difference between male and female patients in their mean age at the time of the surgery or in the MGFA class of the disease. Females had myasthenic symptoms for a longer period of time before surgery (mean, 34.6 versus 20 months). This was not, however, statistically significant (p = 0.08).
No patient died in the postoperative period or during the follow-up period. Half of the patients were extubated immediately after surgery, and 85% were extubated within the first 24 hours of surgery. The median length of intensive care stay was 1 day (range, 0 to 58) and that of the in-hospital stay was 8 days (range, 3 to 75).
Symptoms
At the end of the follow-up, 15 patients (17%) were in complete stable remission, defined as absence of symptoms and not receiving antimyasthenic treatment.
Sixty-seven patients (79%) reported clinical improvement (p < 0.0001), and 63 (74%) were asymptomatic or in stage I on no or minimal treatment (in complete or pharmacological remission or in minimal manifestation class) [8]. The mean postoperative MGFA class was 0.9 ± 0.9 (Fig 1). Thirteen patients (15%) reported no change in their symptoms.
The severity of the disease preoperatively predicted clinical improvement after surgery (p < 0.05), with more advanced stages before surgery associated with bigger symptomatic improvement (p < 0.001). Remission at 1 year predicted remission at the end of follow-up (p = 0.05) (Fig 2). Patient's age, sex, and the duration of symptoms at the time of the surgery, however, did not predict the remission or clinical improvement.
Raised antiacetylcholine receptor antibody titers were found in 96% of patients preoperatively. Neither the presence of a raised value nor the actual value, however, predicted the postoperative remission or symptomatic improvement after surgery.
Pathology
Nine patients (11%) had thymoma, 51 (60%) had hyperplasia, and the thymus was normal in 25 patients (29%).
Older age was a risk factor for having thymic pathology especially thymoma (p < 0.001). The presence of hyperplasia or thymoma, however, did not predict clinical improvement or remission after surgery.
Postoperative Complications
Seventy-two patients (84.7%) had no early or late morbidity. Thirteen patients (15%) had a total of 16 complications during the follow-up period. Eight patients (9%) had major operative complications (Table 3).
Complications were associated with thymoma (p < 0.05) and immunosuppressive drugs before surgery (p = 0.05) (Three of the patients with major complications had thymoma [38%]). The two phrenic nerve palsies were in cases where thymoma involved the nerves.
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Comment
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Thymectomy is well established in the treatment of MG. Controversy, however, remains around the indications for and the extent of surgery. Most clinicians recommend surgery for severe generalized disease refractory to medical treatment. Some, however, question the role of surgery in the treatment of patients with milder symptoms with no evidence of a thymoma on chest imaging.
Our data demonstrate improvement in the vast majority (80%) of patients, after surgery (Fig 1), whatever their preoperative clinical MG status. The finding confirms that clinical improvement is found in patients with even the mildest symptoms. This improvement is lasting (remission at 1-year follow-up predicted the remission at discharge). That remission and clinical improvement in our patients were not predicted by patient's age, sex, duration of disease before surgery, thymic pathology, or antiacetylcholine receptor antibodies titer may expand the indications for surgery. As the absence of thymoma or hyperplasia, furthermore, did not influence the remission or the improvement postoperatively, thymic pathology should not influence the indication for surgery.
The absence of any early or late deaths and the finding that most of the major complications arose in patients who had extensive dissection to remove advanced thymomas demonstrate that the operation is safe. Although there are advocates of more aggressive surgery, these findings demonstrate why transsternal thymectomy is the operation of choice in many institutions.
A question may arise about the low remission rate in our patients. Other series have reported remission rate between 10% and 40% [6, 7, 10–17]. One explanation is that many of our patients were not local and had early discharge to their local center (10%) while they were on drug-weaning regimens. It is probable, therefore, that many more were completely weaned from myasthenic medication later. Given that spontaneous remission of the disease is rare (
1% per annum), the procedure is clearly beneficial [18].
In conclusion, our review demonstrates that transsternal thymectomy for MG is safe and effective in relieving the symptoms of the disease. It benefits all groups of patients, including those presenting at a late stage. The results suggest that it is never too late for thymectomy.
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Acknowledgments
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We would like to thank Professor Newsome-Davies for his permission to include the patients of the Department of Neurology, Radcliffe Infirmary, Oxford, UK.
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References
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Abstract
Introduction
