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May 2010, Volume 60, Issue 5

Original Article

Experience of thymectomy by median sternotomy in patients with myasthenia gravis

Niaz Hussain  ( Department of Thoracic Surgery, Jinnah Postgraduate Medical Centre, Karachi. )
Syed Waqar Ahmed  ( Department of Thoracic Surgery, Jinnah Postgraduate Medical Centre, Karachi. )
Tanveer Ahmed  ( Department of Thoracic Surgery, Jinnah Postgraduate Medical Centre, Karachi. )
Abu Bakar Hafeez  ( Department of Thoracic Surgery, Jinnah Postgraduate Medical Centre, Karachi. )
Roohina Baloch  ( Department of Anesthesiology, Jinnah Postgraduate Medical Centre, Karachi. )
Shoukat Ali  ( Department of Neurology, Jinnah Postgraduate Medical Centre, Karachi. )

Abstract

Objective: To determine the outcome of thymectomy in patients with myasthenia gravis and safety of median sternotomy approach.
Methodology: An observational descriptive study was conducted in the department of thoracic surgery JPMC from February 2005 to January 2009.
Twenty-two patients having persistent generalized or ocular myasthenia gravis referred to our department by neurologists and general physicians, partially or not responding to medical treatment with or without thymoma, were included in the study. Those who were not fit for anaesthesia were excluded. Preoperatively 2 to 3 sessions of plasmapheresis were done and each patient was given anti myasthenia gravis treatment. Clinical staging was done by Modified Osserman classification. Median sternotomy approach was used. Outcome was assessed on the basis of remission of disease in different Osserman groups. All patients were followed for a minimum of 6 months.
Results: Out of 22 patients, 16 (72.7%) were females and 6 (27.2%) males. Mean age at presentation was 35.2 ± 14.5 years. Mean duration of symptoms was 1.5 ± 1.2 years. A total of 4 (18.1%) patients with myasthenia gravis had thymoma and histopathology of 18 (81.9%) patients showed thymic hyperplasia. Remission was seen in most grades of Osserman. The best response was seen in Grade I where all patients achieved remission. Most patients in Grade II A and II B were benefited. The only patient in Grade III had no improvement of symptoms. No patient in Grade IV underwent thymectomy. Overall 86.3 % had a positive outcome on basis of remission and improvement.
Conclusion: Thymectomy by median sternotomy is safe and effective with more favourable outcomes for patients of myasthenia gravis not responding to medical treatment (JPMA 60:368; 2010).

Introduction

The first evidence of a relation between thymus and myasthenia gravis was observed as early as 19011 but it was Blalock and co workers who discovered in 1941 the successful outcomes of thymectomy in these patients.2 Since then it has been widely used as a treatment modality for patients with myasthenia gravis.3 Remission rates of around 80 % have been reported in literature.4,5 Although controversy exists regarding the best surgical approach for removal of the thymus, median sternotomy is considered effective and safe, especially if found at an ectopic location during the procedure.6,7 Data in Pakistan regarding the effectiveness of thymectomy in patients with myasthenia gravis using median sternotomy approach is limited.
In this study, the authors have attempted to determine the outcome of thymectomy in patients with myasthenia gravis and safety of median sternotomy approach in these patients.

Patients and Methods

The study was conducted in the department of thoracic surgery from February 2005 to January 2009.A total of 22 patients who had persistent generalized or ocular myasthenia gravis, referred to our department by neurologists and general physicians, partially or not responding to medical treatment with or without thymoma were included in the study. Most of the patients were referred from the neurology department of the same hospital. C.T scan was done in every patient to evaluate the Thymoma. Patients were evaluated for anaesthesia fitness; those who were not fit due to renal failure, cardiac arrhythmias and chronic liver disease were excluded. All the patients were prepared preoperatively with 2 to 3 sessions of plasmapheresis to decrease the load of antibodies against acetylcholine receptors and every patient was given anti myasthenia gravis treatment even on the morning before surgery.
Clinical staging of patients was performed by modified Osserman classification (Table-1).


A standard median sternotomy approach was used. All thymic tissue and mediastinal fat were removed from the lower limit of the pericardium inferiorly to the cervical thymic extension superiorly and from one phrenic nerve to the other.
Post operatively all patients were kept in Intensive Care Unit until they were vitally stabilized and considered safe to be moved to the ward. They were assessed by neurologists and started on anticholinesterase therapy if any signs of disease was found. Narcotics, muscle relaxants and sedatives were avoided in all patients.
Outcome was assessed on the basis of remission of disease in different Osserman groups. Remission was defined as absence of symptoms of myasthenia gravis or cessation of medical treatment without re appearance of any symptoms. A total of 3 preoperative anti myasthenia gravis treatment groups were identified and then were followed to assess for the development of symptoms post operatively. These groups were:
Group 1: Patients on pyridostigmine alone
Group 2: Patients on pyridostigmine+steroids
Group 3: Patients on pyridostigmine+azathioprine
An extensive assessment of patients post operatively was performed for the development of complications of median sternotomy and they were managed accordingly. All patients were followed for a minimum of 6 months and asked to consult if they experienced any of the signs and symptoms of myasthenia again. Median duration of follow up was 15.5 months.

Results

A total of 22 patients underwent thymectomy using median sternotomy approach. Out of these, 16 (72.7%) were females and 6 (27.2%) were males. The mean age at presentation was 35.2 ± 14.5 years. The mean duration of symptoms was 1.5 ± 1.2 years. A total of 4 (18.1%) patients with myasthenia gravis had thymomas and histopathology of 18 (81.9%) patients showed thymic hyperplasia. Most patients belonged to Class II A of Osserman classification and remission was seen in most grades of Osserman classification (Table-2).


The best response was seen in Grade I where all patients achieved remission. Most patients in Grade II A and II B were also benefited. The only patient in Grade III had no improvement in symptoms. No patient in Grade IV underwent thymectomy. Overall 86.3% had a positive outcome on basis of remission and improvement. Remission was also assessed for different medication groups as shown in Table-3.

Patients in group I showed 77.7% remission. Group 2 and 3 also showed good results with 71.4% and 66.6% remission rates.
The most common major complication after median sternotomy was sternal bleeding that was encountered in 2 (9%) patients. This was followed by disruption of the wound. In minor complications, pneumothorax was the most common occurring in 7 (31.8%) patients. This was followed by wound infection 4 (18%) patients, and 2 (9%) each of haemothorax, and seroma. A total of 2 (9%) patients had intraoperative complications including phrenic nerve and innominate vein injury. No long term morbidity or mortality was observed.

Discussion

Myasthenia gravis (MG) is an autoimmune disorder affecting postsynaptic acetylcholine receptors of voluntary muscles.8 It leads to progressive weakness and fatigue of ocular or extra ocular muscles and can potentially lead to respiratory failure.9 Various studies have demonstrated the significance of different Osserman groups in predicting the likelihood of improvement in patients with myasthenia gravis after thymectomy. Controversy exists and some studies have demonstrated more benefit to patients in severe grades of Osserman classification10-12 and others have concluded with favourable outcomes for mild to moderate myasthenia.9,13 In this study, most patients with mild to moderate disease in grades 1 and 2 of Osserman classification showed greater improvements with patients in Grade 1 achieving 100 % results and Grade II A and II B achieving 90.9% and 83.3% results. A limitation to the study was presence of only one patient in Grade III of Osserman classification. More patients in this grade could have made the comparison more effective.
Medical treatment of MG includes anticholinergics, immunosuppressants, steroids and in severe cases plasmapheresis.10 Khan et al7 showed improvement in 25.92% (n 7/27) of their patients after thymectomy for myasthenia gravis. Improvement was defined as a decrease in the requirement of post operative anti myasthenia medications. In this study 22.7% (n 5/22) patients showed improvement while majority 63.6% (n 14/22) had remission with no requirement of medications post operatively. In this study, the identification of different medication groups before surgery also allowed the authors to determine the effect of thymectomy on reduction in requirement of individual drugs. Patients who were on preoperative pyridostigmine alone showed best remission with 77.7% results.
Surgical treatment is an increasingly accepted procedure for patients with myasthenia gravis.14 Approaches like manubriotomy and transcervical thymectomy have been practiced and have claimed to have their own advantages.15,16 Although earlier trials demonstrated high levels of morbidity and mortality after median sternotomy, a better understanding of pathophysiology of the disease has lead to a dramatic reduction in morbidity and mortality after median sternotomy for thymectomy in the last decade.17-19 Zielinski et al20 have observed no difference in morbidity after less invasive procedures like manubriotomy in comparison with median sternotomy. Trans sternal approach is considered standard and safe by many surgeons1,21 In this study, median sternotomy was used as the sole method of gaining access to thymic tissue. Complications following the procedure were observed and managed accordingly. Major complications constituted a very small percent of total complications. There were 2 episodes of sternal bleeding while one had disruption of the sternum. In minor complications, pneumothorax was the most frequent complication found in 7 (31.8%) patients. All patients were managed accordingly and no mortality or long term morbidity was observed in any of the patients with complications. Kas et al16 demonstrated similar results with pneumothorax being the most common minor complication and very few patients developing major or intraoperaitve complications.

Conclusion

Thymectomy in patients with myasthenia gravis using median sternotomy is a safe and effective approach with more favourable outcomes for patients in mild to moderate grades of Osserman classification and low risk of any long term morbidity or mortality.

References

1.Weigert C. Pathologisch-anatomischer Beitrag zur Erb-schen Krankheit (myasthenia gravis) [in German]. Neurol Zentralbl 1901; 20: 597-601.
2.Blalock A, Harvey AM, Ford RF, Lilienthal JL Jr. The treatment of myasthenia gravis by removal of the thymus gland. J Am Med Assoc 1941; 117: 1529-33.
3.Waitande SS, Thankachen RJ, Philip MA, Shukla V, Korula RJ. Surgical outcome of thymectomy for myasthenia gravis. Indian J Thorac Cardiovasc Surg 2007; 23: 171-5.
4.Rubin JW, Ellison RG, Moore HV, Pai GP. Factors affecting response to thymectomy for myasthenia gravis. J ThoracCardiovasc Surg 1981; 82: 720-8.
5.Clark RE, Marbarger JP, West PN, Spratt JA, Florence JM, Roper CL, et al. Thymectomy for myasthenia gravis in the young adult. Long-term results. J Thorac Cardiovasc Surg 1980; 80: 696-701.
6.Lee CY, Lee JG, Yang WI, Haam SJ, Chung KY, Park IK. Transsternal maximal thymectomy is effective for extirpation of cervical ectopic thymic tissue in the treatment of myasthenia gravis. Yonsei Med J 2008; 49: 987-92.
7.Khan A, Bilal A, Baseer A. Thymectomy for Myasthenia Gravis: Peshawar experience of 27 cases in five years. J Postgrad Med Inst 2007; 21: 238-41.
8.Drachman DB. Myasthenia gravis. N Engl JMed 1994; 330:1797-810.
9.de Perrot M, Licker M, Spiliopoulos A. Factors Influencing Improvement and Remission Rates after Thymectomy forMyasthenia gravis. Respiration 2001; 68: 601-5.
10.Busch C, Machens A, Pichlmeier U, EmskötterT, Izbicki JR. Long-term outcome and quality of life after thymectomy for myasthenia gravis. Ann Surg 1996; 224: 225-32.
11.Bramis J, Pikoulis E, Leppäniemi A, FelekourasE, Alexiou D, Bastounis E. Benefits of early thymectomy in patients with myasthenia gravis. Eur J Surg 1997; 163: 897-902.
12.Kay R, Lam S, Wong KS, Wang A, Ho J. Response to thymectomy in Chinese patients with myasthenia gravis. J Neurol Sci 1994; 126: 84-7.
13.Kattach H, Anastasiadis K, Cleuziou J, Buckley C, Shine B, Pillai R, et al. Transsternal Thymectomy for Myasthenia Gravis: Surgical Outcome. Ann Thorac Surg 2000; 81: 305-8.
14.Venuta F, Rendina EA, De-Giacomo T, Della Rocca G, Antonini G, Ciccone AM, et al. Thymectomy for myasthenia gravis: a 27-years experience. Eur J Cardiothoracic Surg 1999; 15: 621-4.
15.Granetzny A, Hatem A, Shalaby A, Boseila A. Manubriotomy versus Median sternotomy in thymectomy for myasthenia gravis. Evaluation of the pulmonary status. Eur J Cardiothorac Surg 2005; 27: 361-6.
16.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.
17.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: 334-5.
18.Cohn HE, Solit RW, Schatz NJ, Schlezinger N. Surgical treatment in myasthenia gravis. a 27 year experience. J ThoracCardiovasc Surg 1974; 68: 876-85.
19.Molna J, Szobor A. Myasthenia gravis: effect of thymectomy in 425 patients. A 15-year experience. Eur J Cardiothorac Surg 1990; 4: 8-14.
20.Zielinski M, Kuzdza? J, Szlubowski A, Soja J. Comparison of late results of basic transsternal and extended transsternal thymectomies in the treatment of myasthenia gravis. Ann Thorac Surg 2004; 78: 253-8.
21.Kondov G, Trajkovska T, Ljapcev R, Gogova L, Kondova I. Thymectomy in Myasthenia Gravis: Response and Complications. Turkish Respirat J 2005; 6: 1.

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