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Background: Data are limited on the safety and efficacy of robotic thymectomy in patients with myasthenia gravis (MG) older than 60 years at onset. Methods: Patients older than 60 years at MG onset who underwent robotic thymectomy in Charite Universitaetsmedizin Berlin between 2003 and 2017 were potentially eligible for inclusion. The main outcomes were perioperative complications and clinical outcome according to the Myasthenia Gravis Foundation of America Post-Intervention Status. Results: Sixty-eight (25 women, 43 men) of 580 patients with MG who underwent robotic thymectomy were eligible for perioperative analyses (median age at MG onset 67 years, range: 61 to 85 years). The perioperative morbidity rate was 13.2%, and the only perioperative death was due to aortic dissection. Fifty-one patients were available for further analysis with a median follow-up time of 60 months (range: 12 to 263 months). The complete stable remission rate was 7.8%, the improvement rate was 68.6%, and the overall mortality rate was 11.8%. Compared with preoperative use, the mean daily dose of corticosteroid agents was significantly reduced at the last follow-up (17.6 ± 23.6 mg versus 2.6 ± 6.1 mg, p = 0.0001) without increased use of azathioprine (35.9 ± 61.9 mg versus 42.7 ± 59 mg, p = 0.427). After excluding 2 patients seronegative for the anti-acetylcholine receptor antibody, 10 of 49 seropositive patients achieved “good outcome” (including four complete stable remissions, three pharmacologic remissions, and three minimal manifestations 0) which was predicted by being free of concomitant disease (odds ratio 7.307, 95% confidence interval: 1.188 to 44.937, p = 0.032) and Myasthenia Gravis Foundation of America classification I before thymectomy (odds ratio 6.696, 95% confidence interval: 1.259 to 35.620, p = 0.026). Conclusions: Robotic thymectomy seems to be safe and effective in patients with MG older than 60 years at onset with a statistically significant steroid-sparing effect.

In Myasthenia Gravis (MG) thymic pathologies are often present and thymectomy is used as treatment. By flow cytometry we elucidated alterations of naive CD4+ T cell homeostasis in MG patients and patients with thymoma. MG patients showed increased absolute numbers of CD31- centralnaive CD4+ T cells. Thymoma patients displayed a significantly higher fraction of peripheral blood CD31+ thymicnaive T cells. We show an altered naive CD4+ T cell homeostasis in MG patients that might predispose to autoimmunity. Aberrant generation of T cells in thymoma can be detected by an increased frequency of CD31+ thymicnaive CD4+ T cells in the periphery.

BACKGROUND The study aimed to compare the clinical outcomes of patients with juvenile myasthenia gravis (MG) who underwent robotic thymectomy with that of those who only received medication therapy. METHODS We retrospectively reviewed patients who visited our institution for the diagnosis or treatment of MG with an age at onset younger than 18 years. Patients who underwent thymectomy comprised the surgical group and those who received only medication therapy comprised the nonsurgical group. The clinical outcomes were assessed according to the Myasthenia Gravis Foundation of America Post-Intervention Status. RESULTS Forty-seven patients (35 female, 12 male) were included as the surgical group and 20 patients (15 female, 5 male) comprised the nonsurgical group. Significant differences were observed between the surgical and nonsurgical groups in antibody against acetylcholinesterase receptor (91.5% vs 65%; P = .012), disease duration (median 16 [interquartile range, 7-25] months vs 96 [interquartile range, 42-480] months; P < .001), and corticosteroids requirement (53.2% vs 15%; P = .004) at baseline. Kaplan-Meier analysis showed a higher cumulative probability of complete stable remission in the surgical group (P = .002) compared with the nonsurgical group. Moreover, thymectomy (hazard ratio, 3.842; 95% confidence interval, 1.116-13.230; P = .033) and age at onset (hazard ratio, 0.89; 95% confidence interval, 0.80-0.99; P = .037) were still associated with the achievement of complete stable remission in the multivariable analysis. Furthermore, a significant steroid-sparing effect was observed in the surgical group but not in the nonsurgical group. CONCLUSIONS Robotic thymectomy seems to be more effective than medication therapy on juvenile MG in terms of inducing remission and reducing the use of corticosteroids.

In recent years much progress has been made in the investigation of the pathophysiology, characterizing subgroups, and extension of multimodal treatment of myasthenia gravis (MG). This applies especially to the role of thymectomy (Thx). Thymectomy is always indicated for thymoma-associated myasthenia gravis. Furthermore, based on large cohort studies, during recent decades thymectomy has also become a central part of immune-modulating MG therapy in patients without thymoma. The lack of randomized studies, however, caused a certain persistent reluctance as to the significance of thymectomy. The current MGTX trial has shown the effectiveness of thymectomy. A significant improvement of myasthenic complaints and the reduction of immunosuppressive medication was primarily shown for acquired early-onset MG (EOMG) with complete resection of all thymic tissue. Because the MGTX study only included patients younger than 65 years with generalized MG and positive for acetylcholine-receptor antibodies, at present the significance of Thx for other relevant subgroups as juvenile MG, MG in older patients, ocular MG, as well as seronegative patients is under investigation. Even the prevailing opinion of no benefit of thymectomy for MuSk-positive patients probably needs reevaluation based on ambiguous findings. With respect to surgery, based on the exclusive performance of extended median sternotomy for MG in the MGTX, the value of thoracoscopic modifications for thymectomy as a minimally-invasive alternative is currently under evaluation. For clinical reasons further judgment regarding different minimally-invasive thymectomy techniques compared to the conventional open procedures in the form of randomized comparative studies would be required. Currently, however, an experience-based robotic-assisted thoracoscopic unilateral approach to thymectomy meets all requirements related to surgical, clinical-neurological and patient aspects. Ethical reasons, therefore, will lead to other strategies for comparison of different surgical techniques.

Although myasthenia gravis (MG) is a classic autoantibody-mediated disease, T cells are centrally involved in its pathogenesis. In recent years a number of studies have analyzed the role of CD4+ FoxP3+ regulatory T cells (Treg) in the disease with contradictory results. Here, the generation of Treg was significantly reduced in thymoma as compared to thymic hyperplasia and normal thymus tissue (p=0.0002). In the peripheral blood, Treg subsets classified according to CD49d, HELIOS and CD45RA expression changed after thymectomy and in the long-term course of immunosuppression. Compared to healthy volunteers the frequency of CD45RA+FoxP3low Treg was reduced in MG patients in general (p=0.037) and in particular in patients without immunosuppression (p=0.036). In our study, thymectomy and immunosuppressive treatment were associated with changes in Treg subpopulations. The reduced frequency of CD45RA+FoxP3low Treg we observed in MG patients might play a role in MG pathogenesis.

OBJECTIVES This study aimed to compare the outcomes of patients with ocular myasthenia gravis (OMG) who underwent thymectomy before generalization with the outcomes of those who underwent thymectomy after generalization. METHODS We retrospectively reviewed patients who underwent robotic thymectomy for myasthenia gravis between January 2003 and February 2018. Patients who presented with purely ocular symptoms at myasthenia gravis onset were eligible for inclusion. Exclusion criteria were patients who were lost to follow-up and patients who underwent re-thymectomy. Patients with OMG who developed generalization before thymectomy were categorized into gOMG group and those who did not were categorized into OMG group. The primary outcome was complete stable remission according to the Myasthenia Gravis Foundation of America Post-Intervention Status (MGFA-PIS). RESULTS One hundred and sixty-five (66 males and 99 females) out of 596 patients with myasthenia gravis were eligible for inclusion. Of these, there were 73 and 92 patients undergoing thymectomy before and after the generalization of OMG, respectively. After propensity score matching, a data set of 130 patients (65 per group) was formed and evaluating results showed no statistical differences between the 2 groups. The estimated cumulative probabilities of complete stable remission at 5 years were 49.5% [95% confidence interval (CI) 0.345–0.611] in the OMG group and 33.4% (95% CI 0.176–0.462) in the gOMG group (P = 0.0053). Similar results were also found in patients with non-thymomatous subgroup [55 patients per group, OMG vs gOMG, 53.5% (95% CI 0.370–0.656) vs 28.9% (95% CI 0.131–0.419), P = 0.0041]. CONCLUSIONS Thymectomy in OMG before generalization might result in a higher rate of complete stable remission than thymectomy after generalization.

In Myasthenia Gravis (MG) thymic pathologies are often present and thymectomy is used as treatment. By flow cytometry we elucidated alterations of naïve CD4

Approximately, 50% of myasthenia gravis (MG) patients initially present with purely ocular symptoms. Of these, about 60% will develop secondary generalized MG, typically within 2 years. Risk factors for secondary generalization are still controversial. In this study, we reviewed clinical parameters, thymic pathologies and medical treatments of MG patients with purely ocular symptoms at onset to investigate risk factors for secondary generalization. In this monocentric retrospective study, we reviewed consecutive patients who underwent robotic thymectomy between January 2003 and October 2017 in Charite Universitaetsmedizin Berlin. We used univariate and multivariate Cox proportional hazards regression models to identify factors associated with secondary generalization. Survival curves were plotted using Kaplan–Meier method and log-rank tests were performed to analyze the association between corticosteroids use and secondary generalization in subgroups defined by anti-AChR antibody status and thymic pathology. One hundred and eighty of 572 MG patients who underwent robotic thymectomy were eligible for inclusion, of whom 110 (61.1%) developed a secondary generalized MG over a mean follow-up time of 23.6 months. The presence of a thymoma (HR 1.659, 95% CI (1.52–2.617), P = 0.029) was the only risk factor for secondary generalization in our series. Treating with corticosteroids was associated with a lower conversion rate in ocular myasthenia patients with thymic hyperplasia (n = 55, P = 0.028), but not with other thymic pathologies including thymoma and normal or atrophic thymus. The conversion rate in ocular myasthenia was high in our series, predicted by the presence of a thymoma. Our findings suggest that corticosteroids can prevent secondary generalization in ocular myasthenia patients with thymic hyperplasia, which requires further research.

Background Thymectomy is an essential component in the treatment of myasthenia gravis (MG) and the best treatment for localized thymoma. Minimally invasive thymectomy has advanced to include robotic-assisted techniques. The acceptance of this approach is growing rapidly, while the debate on the adequate technique for thymectomy remains open. Methods We describe the technique of robotic-assisted thymectomy and its modifications. The worldwide registries and the literature are reviewed. The experience from the largest single-center database is analyzed. Results The unilateral three-trocar approach for robotic thymectomy from either left or right side has been standardized. More than 100 centers worldwide perform robotic thymectomy. The annual number of this procedure increased steadily and reached 1,000 in 2012, while the largest single-center experiences comprise almost 500 cases. The end points improvement of MG and recurrence of thymoma are comparable to open procedures. There are special advantages of robotic assistance for complete mediastinal dissection. The perioperative complication rate is below 2%. Conclusion Robotic thymectomy combines minimal incisional discomfort with extensive mediastinal dissection. As its use expands, robotic thymectomy may become the standard for all indications of thymectomy.

Thymectomy is necessary for thymic tumors and an essential part of the therapeutic strategy for myasthenia gravis. Within a century, the history of thymectomy has been characterized by the development of minimally-invasive surgical techniques. The latest refinement is robotic-assisted thymectomy. The perioperative management including anesthesia is described. The stepwise operative technique starts with special positioning of the patient. The preferred conduct of the operation is provided. For anatomical reasons the left side is preferred for the unilateral approach. The extended thymectomy is necessary to achieve the best outcome. This includes resection of the contralateral cardiophrenic tissue. Tips for performing the operation are included and pitfalls are described. All essential steps of the operation are illustrated. The advantages of robotic technology optimized by the described approach and consist of surgeon-directed 3-D vision, magnification, multiple arcs of instrument movement, tremorless precision, and potentially the most thorough mediastinal dissection of all minimally invasive surgical options. The review of the supportive literature for thymectomy in the treatment of myasthenia gravis is described; especially the recently published prospective randomized trial comparing medical therapy to thymectomy, showing superiority of thymectomy. It is likely that the impact will increase the number of patients seeking thymectomy.

Robotic thymectomy with the da Vinci robotic system is the latest development in the surgery of thymic gland. Thymectomy for myasthenia gravis is best offered to patients with seropositive acetylcholine receptor antibodies and who are seronegative for muscle-specific kinase protein. The robotic operation technique is indicated in all patients with myasthenia gravis in association with a resectable thymoma, typically Masaoka-Koga stages I and II.

Whether there is a general perturbation of B and plasma cell subsets in myasthenia gravis (MG) has not been investigated so far. Here we performed a detailed flow cytometric analysis of blood and if available thymic tissue in order to detect MG-specific and therapy-induced changes. We observed significant differences in the distribution of B cell subsets in MG patients, yet these were mainly attributable to medical treatment. Furthermore MG is associated with significantly increased frequencies of plasma cells that were especially activated in purely ocular disease manifestation. In contrast to thymoma, B cell subset distribution in hyperplastic thymus could be distinguished from peripheral blood, however both tissues were not significantly enriched with plasma cells. Thus B cell differentiation in general is not defective in MG, but modified by therapy and enhanced frequencies of plasma cells can be detected in MG patients.

ObjectiveRadical thymectomy has become more popular in the comprehensive treatment of myasthenia gravis. Minimally invasive techniques are increasingly used for thymectomy. The most recent development in robotic thoracoscopic surgery has been successfully applied for mediastinal pathologies. To establish robotic technique as a standard, the results of high-volume centers and comparison with traditional surgery are mandatory.MethodsIn a retrospective cohort study, the results of 79 thoracoscopic thymectomies (October 1994 to December 2002) were compared with the results of 74 robotic thoracoscopic thymectomies (January 2003 to August 2006). Data from both series were collected prospectively. In both groups, all patients had myasthenia gravis. Both cohorts were compared with respect to severity of disease, gender, age, histology, and postoperative morbidity. All patients were analyzed for quantification of improvement of disease according to the Myasthenia Gravis Foundation of America.ResultsThere were no differences in age distribution and severity of myasthenia gravis. The dominant histologic finding was follicular hyperplasia of the thymus in both groups with a significantly higher percentage in the thoracoscopic thymectomy series (68% vs 45%, P

Complete thymectomy (Thx) is a crucial part of treatment for myasthenia gravis (MG) and thymoma. The discussion about the necessity of radical, complete Thx and reduced invasiveness has led to no less than 14 different surgical approaches for Thx. The latest development is robotic-assisted surgery. Though its impact on minimally invasive surgery is not yet clear, it seems to be most promising for surgery in remote, narrow anatomical regions like the mediastinum. One hundred six consecutive robotic-assisted thymectomies (rThx) with the da Vinci robotic surgical system were performed between January 2003 and April 2007 in a prospective single-center study. Postoperative morbidity was recorded according to the Myasthenia Gravis Foundation of America (MGFA) classification. With zero mortality, the overall postoperative morbidity rate was 2%. The cumulative complete stable remission rate of MG was > 40% for all patients, and there was no statistical difference as compared to non-thymomatous MG patients. The cumulative rate of minimal manifestations (MM0-MM3) according to the MGFA classification showed a postoperative improvement in quality of life for most of the patients. The da Vinci robotic system allowed for technical refinements of the well-defined operation technique of thoracoscopic Thx (tThx). From the technical point of view, rThx has advantages for mediastinal dissection. rThx had a shorter learning curve. There might be better outcome results for rThx in MG patients, as compared with nonrobotic tThx. Therefore, rThx is a promising technique for minimally invasive Thx.

There are absolute and relative indications for complete removal of the thymus gland. In the complex therapy of autoimmune-related myasthenia gravis, thymectomy plays a central role and is performed with relative indication. In case of thymoma with or without myasthenia, thymectomy is absolutely indicated. Thymus resection is further necessary for cases of hyperparathyroidism with ectopic intrathymic parathyroids or with certain forms of multiple endocrine neoplasia. The transcervical operation technique traditionally reflected the well-founded desire for minimal invasiveness for thymectomy. Due to the requirement of radicality however, most of these operations were performed using sternotomy. With the evolution of therapeutic thoracoscopy in thoracic surgery, several pure or extended minimally invasive operation techniques for thymectomy have been developed. At present uni- or bilateral, subxiphoid, and modified transcervical single or combination thoracoscopic techniques are in use. Recently a very precise new level of thoracoscopic operation technique was developed using robotic-assisted surgery. There are special advantages of this technique for thymectomy. An overview of the development and experiences with minimally invasive thymectomy is presented, including data from the largest series published so far.

Thymectomy is relatively indicated and most frequently performed in patients with the autoimmune disease myasthenia gravis. In particular, the indication for thymectomy, as well as the long-term improvement of myasthenia gravis, may depend on patient-derived factors such as gender, age, the severity of myasthenia, the duration of symptoms, the interval between diagnosis and thymectomy, the presence/absence of a thymoma, the serologic investigation (anti–acetylcholine receptor [anti-AChR], anti–muscle-specific kinase [anti-MuSK], or no antibodies), the amount of medication and necessity of immunosuppression, and other comorbidities. There is an absolute indication for thymectomy in patients with thymoma, an epithelium-derived tumor of the anterior mediastinum that may or may not be accompanied by myasthenia gravis. Other rare indications are ectopic mediastinal intrathymic parathyroid glands and different forms of multiple endocrine neoplasia with anticipated thymic carcinoma.

Thymectomy is a widely accepted treatment for most cases of myasthenia gravis and essential for the treatment of thymoma. The development of a minimally invasive procedure for thymectomy resulted in a variety of approaches for surgery on the thymic gland. The use of thoracoscopy-based techniques has continued to increase, including the latest advance in this field, robotic thymectomy.We review the rapid development and actual use of this approach by examining published reports, worldwide registries, and personal communications and by analyzing our database, which is the largest single-center experience and contains 317 thymectomies until 12/2012. The technical modifications of robotic thymectomy are also described.Since 2001, approximately 3,500 robotic thymectomies have been registered worldwide. Meanwhile, the results of approximately 500 thymectomy cases have been published. Robotic thymectomy is performed most frequently through a standardized unilateral three-trocar approach. All reports describe promising and satisfactory results for myasthenia gravis. For early-stage thymoma, robotic thymectomy is a technically sound and safe procedure with a very low complication rate and short hospital stay. Oncological outcome without recurrences is promising, but a longer follow-up is needed.The unilateral robotic technique can be considered an adequate approach for thymectomy, even with demanding anatomical configurations. Robotic thymectomy has spread worldwide over the last decade because of the promising results in myasthenia gravis and thymoma patients.