Comparative Clinical Outcomes of Thymectomy for Myasthenia Gravis Performed by Extended Transsternal and Minimally Invasive Approaches

doi:10.1016/j.athoracsur.2008.11.040

The Annals of Thoracic Surgery

Volume 87, Issue 2, February 2009, Pages 385-391

Presented at the Forty-fourth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 28–30, 2008.

https://doi.org/10.1016/j.athoracsur.2008.11.040 Get rights and content

Background

Both transsternal and video-assisted thoracoscopic surgery (VATS) approaches are used for thymectomy in myasthenia gravis. We compared outcomes of simultaneous experiences in two institutions: one utilizing the transsternal approach exclusively, the other using VATS procedures for all patients. The Myasthenia Gravis Foundation of America guidelines were used to standardize reporting.

Methods

Between March 1992 and September 2006, 95 thymectomies were performed for myasthenia gravis; 48 by VATS and 47 by transsternal approach. Preoperative classification and postoperative disease status were compared between the groups.

Results

Mean age was 39.8 ± 14.9 (VATS) versus 34.4 ± 13.2 years (transsternal) (p = 0.07); the proportion of females was 52% versus 67% (p = 0.15); and preoperative duration of myasthenia gravis was 27 ± 44 versus 20 ± 45 months (p = 0.43), respectively. Clinical follow up was 89.5% complete at a mean of 6.0 ± 4.0 years and 4.3 ± 2.9 years (p = 0.03). The operative time was 128 ± 34 minutes (VATS) versus 119 ± 27 minutes (transsternal) (p = 0.22). The need for postoperative ventilation was 4.2% versus 16.2% (p = 0.07) and mean length of stay was 1.9 ± 2.6 versus 4.6 ± 4.2 days (p < 0.001). Thymomas were found in 8.3% of VATS versus 13.3% of transsternal patients (p = 0.44). No myasthenia gravis related deaths occurred and 95.8% of the VATS and 97.9% of the transsternal patients were in either complete stable remission, pharmacologic remission, or minimal manifestations status. In the VATS group, 13 of 17 (76.5%) patients stopped prednisone usage after surgery versus 5 of 14 (35.7%) in the transsternal group (p = 0.022).

Conclusions

Thymectomy is an effective treatment in patients with myasthenia gravis with equivalent clinical outcomes obtained by either approach.

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Material and Methods

The study was carried out at University of Texas Southwestern Medical Center at Dallas and Medical City Dallas Hospital with a retrospective chart review of all cases done from March 1992 to June 2006. Preoperative clinical staging was assessed by the MGFA clinical classification [8]. Medication usage and existing comorbidities were also recorded. Patient follow-up was by clinical appointment visits as well as by scripted telephone contact and included information as to patient status as

Results

Ninety-five patients with myasthenia gravis were included in the study, consisting of 48 VATS patients and 47 transsternal patients. Clinical follow-up was 89.5% complete, with a mean follow-up of 6.0 ± 4.0 years (median = 6.1 years) in the VATS group and 4.3 ± 2.9 years (median = 4.2 years) in the transsternal patient group (p = 0.03).

The mean age in the transsternal group was 34.4 ± 13.2 years, versus 39.8 ± 14.9 years in the VATS group. There were no significant differences in patient

Comment

The earliest reported thymectomy in a myasthenia gravis patient was by Schumacher and Roth in 1912 [10]. However, it was the report by Blalock and colleagues [1] in 1941 that led to the widespread adoption of thymectomy in the management of myasthenia gravis. Since that time, both medical and surgical approaches have been advocated in the absence of rigorous randomized trials on which to draw firm conclusions regarding proper management in nonthymomatous myasthenia gravis. Similarly, different

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Myasthenia gravis (MG) has been recognized as a series of heterogeneous but treatable autoimmune conditions. As one of the indispensable therapies, thymectomy can achieve favorable prognosis especially in early-onset generalized MG patients with seropositive acetylcholine receptor antibody. However, poor outcomes, including worsening or relapse of MG, postoperative myasthenic crisis and even post-thymectomy MG, are also observed in certain scenarios. The responses to thymectomy may be associated with the general characteristics of patients, disease conditions of MG, autoantibody profiles, native or ectopic thymic pathologies, surgical-related factors, pharmacotherapy and other adjuvant modalities, and the presence of comorbidities and complications. However, in addition to these variations among individuals, pathological remnants and the abnormal immunological milieu and responses potentially represent major mechanisms that underlie the detrimental neurological outcomes after thymectomy. We underscore these plausible risk factors and discuss the immunological implications therein, which may be conducive to better managing the indications for thymectomy, to avoiding modifiable risk factors of poor responses and adverse outcomes, and to developing post-thymectomy preventive and therapeutic strategies for MG.
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Neurological autoimmune diseases (NADs) are characterized by an aberrant immune response against antigens in the central nervous system or peripheral nervous system (PNS). The wide spectrum of these diseases depends on an individual’s ancestry, immunopathology, and mechanism of injury. Some of the most important autoimmune neurological syndromes include multiple sclerosis, neuromyelitis optica (NMO), Guillain–Barré syndrome, chronic inflammatory demyelinating polyneuropathy, myasthenia gravis (MG), autoimmune encephalitis, and paraneoplastic neurological disorders (PNDs). Patients experience different neurological manifestations based on the localization of the disease process. The importance of NADs is related to an increase in physician awareness of these diseases. Given the large number of diseases described and the plentiful number of factors that are associated with an autoimmune response, the identification of a common immunopathological mechanism that can explain NADs is a challenge. Among the factors studied, previous infections, genetic predisposition, cancer, vitamin D metabolism, and microbiota have been identified. Autoantibodies to various self-antigens have been shown to occur in many of these diseases, including antimyelin oligodendrocyte glycoprotein and antiaquaporin 4 in NMO, anti-N-methyl-d-aspartate receptor in AIE, antiacetylcholine receptor in MG, and others. A genetic component to the pathogenesis is supported by the identification of human leukocyte antigen associations in patients with NADs. Other possible pathogenic mechanisms include molecular mimicry, CD4+ activation, and CD8+ cytotoxicity. Treatment of NADs on reversing the inflammatory pathway activation present in many of these diseases; however, not all forms of immunosuppressive are equally effective. Future research focusing on identifying the roles of genetics and epigenetics in the pathogenesis will help to develop targeted therapies and a more personalized approach to management.
Myasthenia Gravis
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Myasthenia gravis (MG) is an autoimmune disease that leads to muscle weakness and characterized by an increasing loss of muscle strength with repetitive muscle use. MG has a prevalence of 150–250 per million, and an annual incidence of 8–10 per million. It is an autoimmune disease with pathogenic antibodies against the postsynaptic membrane at the neuromuscular junction. Most patients have antibodies against the acetylcholine receptor (AChR), whereas antibodies against muscle-specific kinase (MuSK) and lipotrotein-receptor related protein 4 are much rarer. Thymus is inducing this antibody production in most patients with AChR antibodies.
MG should be treated symptomatically with an acetylcholine esterase inhibitor, usually pyridostigmine. Long-term immunosuppressive drug treatment is necessary in most patients. Prednisolone, azathioprine and mycophenolate mofetil are the most commonly used drugs. Methotrexate, rituximab, cyclosporine, tacrolimus and cyclophosphamide are all considered as beneficial in refractory MG. Thymectomy leads to clinical improvement in selected patients. Intravenous immunoglobulin and plasma exchange are used for acute exacerbations. New treatments include alternative B-cell inhibitors, complement inhibitors, FcRn inhibitors and other drugs with a selective action in the immune system.
Supportive therapy includes physical training programs, weight watching, healthy lifestyle, correction of double vision, and treating comorbidities.
Transcervical Thymectomy Is the Most Cost-Effective Surgical Approach in Myasthenia Gravis
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Extended thymectomy has been proven to improve the course of myasthenia gravis. Retrospective studies demonstrate that several techniques for thymectomy achieve overlapping remission rates. We therefore compared perioperative outcomes and costs among 3 approaches to thymectomy: sternotomy, video and/or robot assisted, and transcervical.
To ensure similar study groups, we excluded patients with >4 cm or invasive tumors and those who underwent less than an extended thymectomy or concurrent procedures. Hospital costs were collected and analyzed by blinded finance personnel.
The final study group consisted of 25 transcervical, 23 video/robot-assisted, and 14 sternotomy subjects. There was a higher incidence of myasthenia gravis in the transcervical and sternotomy groups (P < 0.001) and of thymoma in the video/robot-assisted and sternotomy groups (P = .002). Mean modified Charlson comorbidity score was higher for sternotomy (2.7 ± 2.1, mean ± SD) than transcervical (1.00 ± 0.58; P < .001) and video/robot-assisted (1.13 ± 0.97; P = .001) procedures. There was no difference in complication rates between approaches (P = 0.828). The cost of transcervical thymectomy was 45% of the cost of sternotomy (P < .001), and was 58% of the cost of video/robot-assisted (P = .018) approaches; these differences remained highly significant on multivariate analysis. Transcervical thymectomy had a shorter mean length of stay (1.2 ± 0.5 days) than median sternotomy (4.4 ± 3.5; P < .001), and video/robot-assisted thymectomy (2.4 ± 0.95; P = .045) and “bed cost” were major contributors to the cost difference between the groups.
Transcervical thymectomy, which provides overlapping myasthenia gravis remission rates versus more invasive approaches, is equally safe and far less costly than sternotomy and video/robot-assisted approaches.
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Nine hundred forty-three patients from 395 hospitals underwent thymectomy for stage I to II thymoma. MIT was performed in 31.3% (59.7% robotic, 40.3% thoracoscopic). Over the study period MIT utilization increased from 21.0% to 40.2% (trend test, p < 0.001). R0 resection was achieved in 83.1% of MITs (86.6% stage I, 72.7% stage II) and 79% of OTs (85.5% stage I, 65.8% stage II). In multivariable analyses, the likelihood of incomplete resection (R1/2) was associated with stage II tumors (odds ratio, 2.51) and World Health Organization B3 histology (odds ratio, 3.66). R0 resection was not associated with surgical approach (p = 0.17) and did not vary with tumor size (trend test, p = 0.90). Mortality rates at 30 and 90 days were 0% and 0.5%, respectively. MIT was associated with significantly shorter lengths of stay than OT (–1.03 days [95% confidence interval, –1.68 to –0.38]).
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Original articleGeneral thoracicComparative Clinical Outcomes of Thymectomy for Myasthenia Gravis Performed by Extended Transsternal and Minimally Invasive Approaches

Background

Methods

Results

Conclusions

Section snippets

Material and Methods

Results

Comment

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

Ann Thorac Surg

Ann Thorac Surg

Ann Thorac Surg

Ann Thorac Surg

Ann Thorac Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

Original article
General thoracic
Comparative Clinical Outcomes of Thymectomy for Myasthenia Gravis Performed by Extended Transsternal and Minimally Invasive Approaches