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Ann Thorac Surg 2006;81:305-308
© 2006 The Society of Thoracic Surgeons

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Original article: General thoracic

Transsternal Thymectomy for Myasthenia Gravis: Surgical Outcome

^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).

	Abstract

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
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.

	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.

	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.

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.

	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.

View larger version (16K): [in this window] [in a new window]   Fig 1. Preoperative (left) and discharge (right) Myasthenia Gravis Foundation of America (MGFA) stage.

View larger version (10K): [in this window] [in a new window]   Fig 2. Complete stable remission rate after transsternal thymectomy.

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).

	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.

	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.

	References

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Hassan Kattach Kyriakos Anastasiadis Julie Cleuziou Ravi Pillai Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kattach, H. Articles by Ratnatunga, C. Search for Related Content PubMed PubMed Citation Articles by Kattach, H. Articles by Ratnatunga, C. Related Collections Mediastinum