ATS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Ann Thorac Surg 2009;88:1638-1645. doi:10.1016/j.athoracsur.2009.07.036
© 2009 The Society of Thoracic Surgeons
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Christos Prokakis
Efstratios Koletsis
Efstratios Apostolakis
Nikolaos Baltayiannis
Dimitrios Dougenis
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Prokakis, C.
Right arrow Articles by Dougenis, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Prokakis, C.
Right arrow Articles by Dougenis, D.
Related Collections
Right arrow Mediastinum
Right arrowRelated Article

Original Articles: General Thoracic

Modified Maximal Thymectomy for Myasthenia Gravis: Effect of Maximal Resection on Late Neurologic Outcome and Predictors of Disease Remission

Christos Prokakis, MDa, Efstratios Koletsis, MD, PhDa,*, Stavroula Salakou, MD, PhDb, Efstratios Apostolakis, MD, PhDa, Nikolaos Baltayiannis, MDc, Antonios Chatzimichalis, MDc, Theodoros Papapetropoulos, MD, PhDb, Dimitrios Dougenis, MD, PhDa

a Cardiothoracic Surgery Department, School of Medicine, Patras University, Patras, Greece
b Department of Neurology, School of Medicine, Patras University, Patras, Greece
c Department of Thoracic Surgery, Metaxa Hospital, Piraeus, Greece

Accepted for publication July 23, 2009.

* Address correspondence to Dr Koletsis, 31 Chlois St, Voula, Athens, 16673, Greece (Email: ekoletsis{at}hotmail.com).


   Abstract
Top
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 References
 
Background: Although thymectomy is a standard practice of care in patients with myasthenia gravis, the best approach to thymic resection remains controversial. This study was conducted to assess the effect of maximal resection on neurologic outcome and identify predictors of disease remission.

Methods: Data of 78 myasthenic patients who underwent modified maximal thymectomy during a 17-year period were retrospectively analyzed. The primary study end point was the achievement of complete remission. Separate analysis was performed for thymoma and nonthymoma patients regarding the factors predicting the neurologic outcome.

Results: No patients died perioperatively. Surgical morbidity was 7.7%. The rate of postoperative myasthenic crisis was 3.8%. Thymoma and nonthymoma patients experienced comparable complete stable remission prediction (74.5% vs 85.7% at 15 years; p = 0.632). The absence of steroids in the preoperative medical treatment was statistically related to the prediction for complete stable remission in both thymoma (95% confidence interval [CI], 2.687 to 339.182, p = 0.006) and nonthymoma patients (95% CI, 1.607 to 19.183; p = 0.007) in multivariate analysis. In thymomatous myasthenia gravis, there was a statistically significant association between disease remission and the World Health Organization (WHO) histologic classification (95% CI, 0.262 to 0.827; p = 0.009).

Conclusions: Maximal resections are recommended in myasthenic patients. Disease severity represents the prime determinant of the neurologic outcome after thymectomy. The neurologic outcome in patients after thymectomy may be statistically associated with the WHO classification subtypes but not necessarily with the aggressiveness of these tumors.


   Introduction
Top
 Abstract
 Introduction
Material and Methods
 Results
 Comment
 References
 
Thymectomy is a valid approach—and is often the treatment of choice—for the management of patients with myasthenia gravis (MG). Although Gronseth and Barohn [1] reviewed previously published data and failed to establish a clear benefit for thymectomy, they documented that MG patients undergoing thymectomy are more likely to achieve medication-free remission and improvement. The rationale for thymectomy in MG is based on the presence of thymic abnormalities, mostly follicular hyperplasia and less frequently thymic tumors in up to 75% [2] of the patients.

The most appropriate surgical approach for the thymic resection is still controversial, however, mainly due to the lack of randomized trials. Transcervical approaches are theoretically associated with lower rates of mortality and morbidity; whereas, transsternal approaches, characterized by a more radical resection of the thymus and the surrounding mediastinal fat, may eventually provide better long-term neurologic improvement. Jaretzki [3] was the first to describe a combined approach, defined as maximal thymectomy, and proposed this as the treatment of choice for MG patients, with excellent disease remission reported for nonthymomatous MG.

The purpose of this study is to assess the effect of a modified technique of maximal thymectomy on the achievement of complete stable remission (CSR) and to identify the factors predicting disease remission for both thymoma and nonthymoma patients.


   Material and Methods
Top
 Abstract
 Introduction
 Material and Methods
Results
 Comment
 References
 
This study was approved by the Hospital Ethics Committee at Patras Medical School.

Patient Data
Data of 78 patients who underwent thymectomy for MG during a 17-year period (1990 to 2007) were evaluated retrospectively (Table 1). The diagnosis of MG was based on clinical and electromyographic evaluation. The indications for thymectomy included generalized nonthymomatous MG, ocular MG refractory to medical treatment, and evidence of thymoma.


View this table:
[in this window]
[in a new window]

  		Table 1 Clinical and Pathologic Patient Data
 
The preoperative workup consisted of lung function testing, echocardiography, and chest computed tomography (CT) or magnetic resonance imaging, or both, to assess the presence of thymoma. Preoperative disease severity was established according to the modified Osserman classification (Table 2). Preoperative medical treatment was assigned by the referring neurologists. The World Health Organization (WHO) histologic classification and Masaoka staging system were used to evaluate thymoma patients. The evaluation of the neurologic outcome at the end of the follow-up period was performed according the Myasthenia Gravis Foundation of America (MGFA) classification [4].


View this table:
[in this window]
[in a new window]

  		Table 2 Modified Osserman Classification
 
Surgical Technique
The operative technique for all patients was defined as modified maximal thymectomy [5]. This procedure is analogous to the T-4 maximal thymectomy described by Jaretzki and Wolff [6] and similar to the extended cervicomediastinal thymectomy reported by Bukley and colleagues [7]. The operation is performed through median sternotomy. The upper incision flaps are elevated up to the thyroid gland to achieve cervical exposure for perithymic and fatty tissue resection. Before any manipulation of the thymus, the brachiocephalic vein is mobilized and the thymic veins are identified and ligated. This avoids the release in the circulation of thymic humoral factors that may precipitate a myasthenic crisis in the immediate postoperative period.

Sharp dissection is performed of the mediastinal fat from the pericardium. The thymus is then excised en block with the mediastinal and cervical fat up to the thyroid isthmus. The resection includes both mediastinal pleuras down to the phrenic neurovascular bundles to ensure the resection of foci of ectopic thymic tissue frequently located at this level. In case of an invasive thymic tumor, a similar resection, en block with the invaded lung parenchyma, pericardium, phrenic nerve, and brachiocephalic vein, is performed.

Study End Point and Follow-Up
The end point of the study was the achievement of CSR, defined as the absence of symptoms and signs of MG for at least 1 year without any medical treatment for MG during that period [4]. The neurologic outcome was evaluated by neurologic examination and was completed in June 2009. Thymoma patients were evaluated annually with chest CT for thymoma recurrence.

Evaluated Predictors of Outcome
The patients were divided in two groups according to the presence of thymoma, and the factors affecting the neurologic outcome were analyzed separately. In nonthymomatous MG, the evaluated prognostic factors of CSR included gender, thymic histology (atrophy/hyperplasia), age at the onset of myasthenia (≤40 vs >40), time elapsed between diagnosis and thymectomy (≤1 year vs >1 year), preoperative steroid treatment, and Osserman stage. In thymoma patients, the statistical analysis of CSR prediction was conducted according the variables of gender, MG onset age (≤40 vs >40 years), Masaoka stage, Osserman stage, preoperative steroid therapy, time between diagnosis and thymectomy (≤1 year vs >1 year), and WHO histologic classification.

Statistical Analysis
Statistical analysis was done with the SPSS 17 software (SPSS Inc, Chicago, IL). Values for continuous data are presented as mean ± standard deviation and range. The {chi}2 and Fischer exact tests were used to compare categoric variables, and the t test was applied to compare continuous variables. Kaplan-Meier life-table analysis was performed, and the log-rank test was used to evaluate the effect of the variables examined on the distribution of CSR over time. The Cox proportional hazard model was applied to verify the concurrent effect of the evaluated factors on CSR. Values of p ≤ 0.05 were considered to be statistically significant.


   Results
Top
 Abstract
 Introduction
 Material and Methods
 Results
Comment
 References
 
Postoperative Outcome
No patients died perioperatively. Surgical morbidity occurred in 6 of 78 patients (7.7%) and included pneumothorax in 2, sternal wound infection in 2, deep vein thrombosis in 1, and recurrent laryngeal nerve injury in 1. Postoperative respiratory insufficiency developed in 7 patients (9%). Myasthenic crisis was documented in 3 patients, and cholinergic crisis in 4 patients after pyridostigmine administration was readministered.

Mean hospital stay was 6.4 ± 2.6 days (range, 4 to 17 days). All but 5 patients were discharged receiving pyridostigmine and oral prednisone. The referring neurologists initiated further adjustment of the patients' medical treatment.

Long-term Neurologic Outcome
The crude CSR rate was 39.7% (31 of 78 patients), and the CSR prediction was 14.9%, 50.6%, and 80% at 5, 10, and 15 years, respectively (Fig 1). Patients with and without thymoma experienced comparable neurologic outcome (Fig 2).


Figure 1
View larger version (17K):
[in this window]
[in a new window]

  		Fig 1. Complete stable remission (CSR) is shown for the total cohort, with vertical ticks designating censored patients.

 

Figure 2
View larger version (16K):
[in this window]
[in a new window]

  		Fig 2. Complete stable remission (CSR) is shown in thymoma patients (dashed line) compared with nonthymoma patients (solid line). Censored thymoma patients are designated by vertical ticks and censored nonthymoma patients by triangles.

 
Nonthymomatous MG
Nonthymomatous MG was present in 51 patients (65.4%), 18 men and 33 women, with a mean age of 34.9 ± 13.2 years (range, 16 to 75 years). The crude CSR rate was 37.3% (19 of 51 patients). The status at the end of follow-up after thymectomy is summarized in Table 3. The time elapsed between thymectomy and CSR was 21.06 ± 18.22 months (range, 0 to 60 months). The CSR prediction was 8.4%, 51.1%, and 85.7% at 5, 10, and 15 years, respectively (Fig 2). The absence of steroids in the preoperative treatment was the only factor statistically predicting CSR in both univariate and multivariate analysis (Fig 3, Table 4).


View this table:
[in this window]
[in a new window]

  		Table 3 Status After Thymectomy at the End of Follow-up According to the Myasthenia Gravis Foundation of America Classification
 

Figure 3
View larger version (16K):
[in this window]
[in a new window]

  		Fig 3. The effect of steroid treatment (dashed line) and no steroid treatment (solid line) is shown on complete stable remission (CSR). Steroid-censored patients are designated by vertical ticks and nonsteroid-censored patients by triangles.

 

View this table:
[in this window]
[in a new window]

  		Table 4 Univariate (Kaplan-Meier) and Multivariate (Cox Regression) Analysis of Predictors of Complete Stable Remission
 
Thymoma-Associated MG
MG was the paraneoplastic manifestation of a thymic tumor in 27 patients (34.6%), 10 men and 17 women, with a mean age of 50.19 ± 15.85 years (range, 18 to 81 years). Table 5 describes the WHO classification types and Masaoka stages. The crude CSR was 44.4% (12 of 27 patients), and the time elapsed between thymectomy and CSR was 19.58 ± 13.18 months (range, 0 to 36 months). The neurologic outcome at the end of follow-up in thymoma patients is reported in Table 3. CSR prediction was 27.1%, 49.1%, and 74.5% at 5, 10, and 15 years, respectively (Fig 2). The WHO histologic classification and absence of preoperative steroid treatment were the only prognosticators of CSR (Figs 4 and 5; Go Table 4).


View this table:
[in this window]
[in a new window]

  		Table 5 WHO Classification and Masaoka Stages of Thymic Tumors
 

Figure 4
View larger version (17K):
[in this window]
[in a new window]

  		Fig 4. Complete stable remission (CSR) in thymoma patients is shown according to the World Health Organization (WHO) histologic classification of thymic tumors.

 

Figure 5
View larger version (14K):
[in this window]
[in a new window]

  		Fig 5. Effect of preoperative steroids (dashed line) compared with no steroids (solid line) is shown on the complete stable remission (CSR) prediction in thymoma patients. Steroid-censored patients are designated by vertical ticks and nonsteroid-censored patients by triangles.

 

   Comment
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
References
 
Although thymectomy represents the standard practice of care in patients with MG, the best approach to thymic resection is debated. The ideal thymectomy should achieve the removal of all thymic tissue to eliminate the autoimmune process that sustains the development of myasthenic symptoms. On the basis of the results reported by Jaretzki and Wolff [6] on a wide distribution of foci of ectopic thymic tissue in both mediastinum and neck, it seems logical to assume that an extended cervicomediastinal dissection may provide better chances for disease remission.

Maximal thymectomy has been associated with an excellent neurologic outcome, but only a few reports have described this approach. Most surgeons are reluctant to perform maximal resections, raising concerns about the safety of the procedure and the absence of definitive evidence demonstrating that maximal resection is more effective in achieving disease remission compared with extended thymectomy [8–10]. The use of CSR as the prime outcome measure for the assessment of the postinterventional status in MG and its evaluation by using life-table analyses, as recommended by Jaretzki [11], may set aside a great part of the controversy on maximal thymectomy.

Despite the high morbidity of 33% reported by Bulkley and colleagues [7], maximal resection should be considered a safe approach. The surgical morbidity in our study was 7.7%, with major complications occurring in only 4 patients. Jaretzki [3] and Essa [12] and their colleagues documented complication rates of 7.3% and 6.5%, respectively. These figures compare favorably with those reported in series of transsternal [13] and VATS thymectomy [14, 15]. Moreover, similar morbidity was found in studies evaluating transcervical thymectomy, with most of the complications being minor [16, 17].

The 3.8% incidence of postoperative myasthenic crisis was lower in the current study than the rate documented in previous series of maximal and extended transsternal thymectomy [7, 13, 18, 19]. This advantage of our technique could be mostly attributed to the exclusion of the thymic veins before any thymic manipulation, leading to a reduced release in the circulation of thymic factors that may precipitate a myasthenic crisis in the early postoperative period.

Nerve injury is the most feared and devastating complication after thymectomy for MG. In the current series, recurrent laryngeal nerve injury was documented in 1 patient with invasive thymoma. Extended resections in the area of the aortopulmonary window and in the neck may theoretically increase the risk for both recurrent laryngeal and phrenic nerve damage. Kas and colleagues [13], however, reported that the rate for each of these injuries varies from 0% to 4.5%, without significant differences between extended transsternal and maximal resections.

The primary objective in performing modified maximal thymectomy is the excision of the whole thymic tissue, avoiding a cervical incision in addition to sternotomy. This approach is highly effective in extirpating the cervical ectopic thymic tissue, which has a reported prevalence of 10% to 63% [3, 14, 20]. At the moment, the presumption of the favorable effect of this tissue on the neurologic outcome after thymectomy has never been demonstrated. Nevertheless, the excellent neurologic outcome reported in series of maximal thymectomy and the evidence that extended transcervical thymectomy may provide remission rates comparable with those of transsternal approaches indicate that this effect is more than insignificant.

The results in nonthymomatous MG in the present study are definitively superior to the results reported in series of transcervical thymectomy [17, 21] and reflect the inability of the transcervical approach to achieve removal of the entire gland, regardless of the exposure achieved through the neck incision. On the contrary, the long-term prognosis at 10 years is comparable to the outcome reported in previous studies of extended transsternal thymectomy [9, 18, 22]. However, a significantly better improvement was noted in the present study (Figs 1 and 2) as the follow up further increased, similar to the observations made by Jaretzki and colleagues [3] and El-Medany and colleagues [23], who performed an analogous resection. Thus, the high probability for CSR not only advocates for the extended resection to be performed but also delineates the need for long-term follow-up to evaluate more effectively the effect of thymectomy on the course of MG.

Thymoma has been reported as a factor associated with worse neurologic outcome and symptom relapse after thymectomy [3, 22, 24]. Our findings seem to be quite different from those observations: our thymoma patients showed a high crude CSR rate of 44.4% and high CSR prediction at 10 and 15 years of follow-up (Fig 2). Kim and colleagues [25] focused on lower Masaoka stages and earlier intervention and considered them as possible explanations for the comparable neurologic outcome found between thymoma and nonthymoma patients. Although the first explanation could be valid in our series, where only 3 of 27 thymoma patients presented with advanced-stage tumor, the second one seems less plausible because 70.3% of thymoma patients had early surgical interventions compared with 54.9% in nonthymomatous MG (p = 0.184).

In addition, the implementation of a standardized maximal resection in all thymoma patients was probably associated with a significantly lower likelihood of remnant thymic tissue, which may well explain (1) the absence of thymoma recurrence and (2) the absence of MG recurrence among the patients who achieved CSR. Therefore, thymoma should not necessarily be considered a negative prognostic determinant of the neurologic outcome after thymectomy.

Recently, there has been interest in minimally invasive approaches to thymic resection. With only a few series of thymectomy using a video-assisted thoracoscopic surgical (VATS) approach reporting life-table analysis, the preliminary results seem rather promising [15, 26]. Nevertheless, the inability to access the neck and excise the cervical adipose tissue and the difficulty to safely reach the upper mediastinum represent potential limitations of the VATS approach that may decrease its validity as the follow-up period increases in these series. The use of robotic systems may facilitate access in difficult to reach areas and may increase the ability for a safe, and eventually more complete, mediastinal dissection [27, 28]. Combined approaches that include VATS thymectomy have been associated with high crude CSR rates and high CSR prediction and may prove to be more effective in achieving disease remission [14, 29].

The absence of steroids in the preoperative treatment of myasthenic patients was an independent predictor of CSR in both study groups similarly to the observations of other authors [22, 26]. It might be logical to anticipate that the initiation of steroids indicates a decline in the patient's clinical condition and insufficient symptom control by the anticholinesterase drug therapy. Although this implies that more severe disease is associated with worse outcome after thymectomy, the preoperative Osserman stage had no effect in predicting CSR in either group of myasthenic patients.

In a previous study revealing the same inconsistency between steroid use and Osserman stage, Park and colleagues [22] proposed a more objective evaluation of disease severity using the MGFA classification. This evaluation could be further enhanced by the incorporation of immunochemical variables and oncogene expression that seem to affect the late outcome after thymectomy [5, 30–32].

In our previous reports on the potential role of the apoptotic oncoproteins bax and bcl-2 and cell proliferation-marker Ki67, we have found that bcl-2 expression was higher in hyperplasia and thymomas compared with thymic carcinomas (p < 0.001), whereas bax and Ki67 expression was higher in carcinomas (p < 0.001). The statistical analysis documented a positive correlation between bax(+) and Ki67(+) cells and MG stage, and a reversible correlation was found between bcl-2(+) cells and the Osserman stage. We therefore concluded that increased apoptosis and proliferation are associated with advanced stage disease [5]. We have further reported that:

1 the bax/bcl-2 ratio may up-regulate caspase-3 expression and modulate apoptosis associated with progress of the disease;
2 patients in CSR (bax/bcl-2 ratio < 1) experienced higher disease-free survival than those who failed to reach CSR (ratio > 1; p = 0.0082); and
3 the bax/bcl-2 ratio was an independent predictive marker for therapeutic response after thymectomy in multivariate analysis (95% CI, 1.078 to 44.073; p = 0.041) [32].

An interesting finding of the present study is the statistically significant association between the WHO classification subtypes and the achievement of CSR in thymoma-associated MG in both univariate and multivariate analysis. An analogous observation was reported by Lopez-Cano and colleagues [33] using the Müller-Hermelink classification. We found that types A, B2, and B3 thymomas reached a high CSR prediction, whereas none of the patients with type AB, B1, and C tumors achieved CSR. These figures indicate that the neurologic outcome after thymectomy in thymomatous MG is probably related to factors different from those defining the malignant behavior of these tumors. Further studies are required to identify the molecular basis of this association, focusing mostly on the increased expression of antibodies against striated muscle antigens in thymoma patients and oncogenes that affect both MG prognosis and its neurologic outcome after thymectomy [5, 32, 34, 35].

In conclusion, we advocate maximal resections for the management of MG because the removal of all the ectopic thymic tissue may warrant better long-term prognosis. Modified maximal thymectomy is a safe and efficient approach in achieving disease remission in both thymoma and nonthymoma patients. Better neurologic outcome should be awaited in patients with less severe disease at the time of operation. The definition of the severity of the disease probably requires a new classification system where the expression of immunochemical markers and oncogenes are used to enhance the validity of the MGFA scoring system. The neurologic outcome after thymectomy in thymomatous MG may be associated with the WHO classification subtypes, but not necessarily with the aggressiveness of these tumors.


   References
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 

  1. Gronseth GS, Barohn RJ. Practice parameter: thymectomy for autoimmune myasthenia gravis (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology Neurology 2000;55:7-15.[Free Full Text]
  2. Jaretzki A, Steinglass KM, Sonett JR. Thymectomy in the management of myasthenia gravis Semin Neurol 2004;24:49-62.[Medline]
  3. Jaretzki 3rd A, Penn AS, Younger DS, et al. "Maximal" thymectomy for myasthenia gravis. Results. J Thorac Cardiovasc Surg 1988;95:47-57.
  4. Jaretzki 3rd A, Barohn RJ, Ernstoff RM, et al. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Myasthenia Gravis: recommendations for clinical research standards. Ann Thorac Surg 2000;70:327-334.[Free Full Text]
  5. Salakou S, Tsamandas AC, Bonikos DS, Papapetropoulos T, Dougenis D. The potential role of bcl-2, bax and Ki67 expression in thymus of patients with myasthenia gravis and their correlation with clinicopathologic parameters Eur J Cardiothorac Surg 2001;20:712-721.[Abstract/Free Full Text]
  6. Jaretzki 3rd A, Wolff M. Maximal thymectomy for myasthenia gravis. Surgical anatomy and operative technique. J Thorac Cardiovasc Surg 1988;96:711-716.[Abstract]
  7. Bulkley GB, Bass KN, Stephenson GR, et al. Extended cervicomediastinal thymectomy in the integrated management of myasthenia gravis Ann Surg 1997;226:324-334.[Medline]
  8. Bril V, Kojic J, Ilse WK, Cooper JD. Long term clinical outcome after transcervical thymectomy for myasthenia gravis Ann Thorac Surg 1998;65:1520-1522.[Abstract/Free Full Text]
  9. Masaoka A, Yamakawa Y, Niwa H, et al. Extended thymectomy for myasthenia gravis patients: a 20-year review Ann Thorac Surg 1996;62:853-859.[Abstract/Free Full Text]
  10. Scott W, Detterbeck F. Transsternal thymectomy for myasthenia gravis Semin Thorac Cardiovasc Surg 1999;11:54-58.[Medline]
  11. Jaretzki 3rd A. Thymectomy for myasthenia gravis: analysis of controversies-patient management Neurologist 2003;9:77-92.[Medline]
  12. Essa M, El-Medany Y, Hajjar W, et al. Maximal thymectomy in children with myasthenia gravis Eur J Cardiothorac Surg 2003;24:187-189.[Abstract/Free Full Text]
  13. 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;72:1691-1697.[Abstract/Free Full Text]
  14. Zielinski M, Kuzdzal J, Szlubowski A, Soja J. Transcervical-subxiphoid-thoracoscopic maximal thymectomy—operative technique and early results Ann Thorac Surg 2004;78:404-409.[Abstract/Free Full Text]
  15. Tomulescu V, Ion V, Kosa A, Sgarbura O, Popescu I. Thoracoscopic thymectomy mid-term results Ann Thorac Surg 2006;82:1003-1007.[Abstract/Free Full Text]
  16. Calhoun RF, Ritter JH, Guthrie TJ, et al. Results of transcervical thymectomy for myasthenia gravis in 100 consecutive patients Ann Surg 1999;230:555-559.[Medline]
  17. Khicha SG, Kaiser LR, Shrager JB. Extended transcervical thymectomy in patients with myasthenia gravis Ann N Y Acad Sci 2008;1132:336-343.[Medline]
  18. Sekine Y, Kawaguchi N, Hamada C, et al. Does perioperative high-dose prednisolone have clinical benefits for generalized myasthenia gravis? Eur J Cardiothorac Surg 2006;29:908-913.[Free Full Text]
  19. Watanabe A, Watanabe T, Obama T, et al. Prognostic factors for myasthenic crisis after transsternal thymectomy in patients with myasthenia gravis J Thorac Cardiovasc Surg 2004;127:868-876.[Abstract/Free Full Text]
  20. Ashour M. Prevalence of ectopic thymic tissue in myasthenia gravis and its clinical significance J Thorac Cardiovasc Surg 1995;109:632-635.[Abstract/Free Full Text]
  21. Papatestas AE, Genkins G, Kornfeld P, et al. Effects of thymectomy in myasthenia gravis Ann Surg 1987;206:79-88.[Medline]
  22. Park IK, Choi SS, Lee JG, Kim DJ, Chung KY. Complete stable remission after extended transsternal thymectomy in myasthenia gravis Eur J Cardiothorac Surg 2006;30:525-528.[Abstract/Free Full Text]
  23. El-Medany Y, Hajjar W, Essa M, Al-Kattan K, Hariri Z, Ashour M. Predictors of outcome for myasthenia gravis after thymectomy Asian Cardiovasc Thorac Ann 2003;11:323-327.[Abstract/Free Full Text]
  24. Hsu HS, Huang CS, Huang BS, et al. Thymoma is associated with relapse of symptoms after transsternal thymectomy for myasthenia gravis Interact Cardiovasc Thorac Surg 2006;5:42-46.[Abstract/Free Full Text]
  25. Kim HK, Park MS, Choi YS, et al. Neurologic outcomes of thymectomy in myasthenia gravis: comparative analysis of the effect of thymoma J Thorac Cardiovasc Surg 2007;134:601-607.[Abstract/Free Full Text]
  26. Mantegazza R, Baggi F, Bernasconi P, et al. Video-assisted thoracoscopic extended thymectomy and extended transternal thymectomy (T-3b) in non-thymomatous myasthenia gravis patients: remission after 6 years of follow up J Neurol Sci 2003;212:31-36.[Medline]
  27. Augustin F, Schmid T, Sieb M, Lucciarini P, Bodner J. Video-assisted thoracoscopic surgery versus robotic-assisted thoracoscopic surgery thymectomy Ann Thorac Surg 2008;85:S768-S771.[Free Full Text]
  28. Fleck TM, Fleck M, Mueller M, et al. Extended videoscopic robotic thymectomy with the da Vinci telemanipulator for the treatment of myasthenia gravis: the Vienna experience Interact Cardiovasc Thorac Surg 2009[Epub ahead of print].
  29. De Perrot M, Bril V, McRae K, Keshavjee S. Impact of minimally invasive trans-cervical thymectomy on outcome in patients with myasthenia gravis Eur J Cardiothorac Surg 2003;24:677-683.[Abstract/Free Full Text]
  30. Deymeer F, Gungor-Tuncer O, Yilmaz V, et al. Clinical comparison of anti-MuSK vs anti-AChR positive and sieronegative myasthenia gravis Neurology 2007;68:609-611.[Abstract/Free Full Text]
  31. Ponseti JM, Caritg N, Gamez J, López-Cano M, Vilallonga R, Armengol M. A comparison of long term post-thymectomy outcome of anti-AChR positive, anti-AChR negative and anti-MuSK positive patients with non thymomatous myasthenia gravis Expert Opin Biol Ther 2009;9:1-8.[Medline]
  32. Salakou S, Kardamakis D, Tsamandas AC, et al. Increased Bax/Blc-2 ratio upregulates caspase-3 and increases apoptosis in thymus of patients with myasthenia gravis In Vivo 2007;21:123-132.[Abstract/Free Full Text]
  33. Lopez-Cano M, Ponseti-Bosch JM, Espin-Basany E, Sanchez-Garcia JL, Armengol-Carrasco M. Clinical and pathological predictors of outcome in thymoma-associated myasthenia gravis Ann Thorac Surg 2003;76:1643-1649.[Abstract/Free Full Text]
  34. Chen XJ, Qiao J, Xiao BG, Lu CZ. The significance of titin antibodies in myasthenia gravis–correlation with thymoma and severity of myasthenia gravis J Neurol 2004;251:1006-1011.[Medline]
  35. Skeie GO, Aarli JA, Gilhus NE. Titin and ryanodine receptor antibodies in myasthenia gravis Acta Neurol Scand Suppl 2006;183:19-23.[Medline]

Related Article

Invited Commentary
Cameron Wright
Ann. Thorac. Surg. 2009 88: 1646. [Extract] [Full Text] [PDF]



This article has been cited by other articles:


Home page
 Ann. Thorac. Surg.Home page
C. Wright
Invited Commentary
Ann. Thorac. Surg., November 1, 2009; 88(5): 1646 - 1646.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Christos Prokakis
Efstratios Koletsis
Efstratios Apostolakis
Nikolaos Baltayiannis
Dimitrios Dougenis
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Prokakis, C.
Right arrow Articles by Dougenis, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Prokakis, C.
Right arrow Articles by Dougenis, D.
Related Collections
Right arrow Mediastinum
Right arrowRelated Article

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS