Aktuelle Neurologie 2018; 45(04): 263-270
DOI: 10.1055/a-0582-9020
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Thymektomie bei Myasthenia gravis

Thymectomy in Myasthenia gravis
Jens Carsten Rückert
1   Kompetenzzentrum für Thoraxchirurgie (CCM,CVK,CBF) Chirurgische Klinik Campus Charité Mitte/Campus Virchow-Klinikum; Charité – Universitätsmedizin Berlin
,
Marc Swierzy
1   Kompetenzzentrum für Thoraxchirurgie (CCM,CVK,CBF) Chirurgische Klinik Campus Charité Mitte/Campus Virchow-Klinikum; Charité – Universitätsmedizin Berlin
,
Siegfried Kohler
2   Integriertes Myasthenie Zentrum, Klinik für Neurologie, NeuroCure Clinical Research Center, Charité – Universitätsmedizin Berlin
,
Andreas Meisel
2   Integriertes Myasthenie Zentrum, Klinik für Neurologie, NeuroCure Clinical Research Center, Charité – Universitätsmedizin Berlin
,
Mahmoud Ismail
1   Kompetenzzentrum für Thoraxchirurgie (CCM,CVK,CBF) Chirurgische Klinik Campus Charité Mitte/Campus Virchow-Klinikum; Charité – Universitätsmedizin Berlin
› Author Affiliations
Further Information

Publication History

Publication Date:
03 May 2018 (online)

Zusammenfassung

Die Myasthenia gravis (MG) hat in den letzten Jahren zahlreiche Fortschritte in der Erforschung der Pathophysiologie, der Charakterisierung von Subgruppen sowie der Erweiterung der multimodalen Therapie erfahren. Insbesondere gilt das auch für die Rolle der Thymektomie (Thx). Für die Thymom-assoziierte MG ist die Thx streng indiziert. Auf Basis großer Kohortenstudien über die letzten Jahrzehnte wurde die Thx aber auch zentraler Bestandteil der immunmodulierenden MG-Therapie bei MG-Patienten ohne Thymom-Nachweis. Da randomisierte Studien fehlten, blieb jedoch eine Restunsicherheit zum Stellenwert der Thx. In der MGTX-Studie konnte die Wirksamkeit der Thx nun zweifelsfrei nachgewiesen werden [1]. Eine signifikante Verbesserung der myasthenen Beschwerden und die Reduktion der immunsuppressiven Medikamente zeigten sich vor allem für die im jungen Erwachsenenalter erworbene MG (EOMG) bei Durchführung einer kompletten Resektion des Thymusgewebes. Da die MGTX-Studie nur Patienten mit generalisiertem Verlauf und Acetylcholinrezeptor-Antikörpernachweis eingeschlossen hatte, die jünger als 65 Jahre waren, wird derzeit die Bedeutung der Thx bei den anderen relevanten Subgruppen, wie der juvenilen MG, der Altersmyasthenie, der okulären MG sowie den Patienten mit fehlendem Autoantikörper-Nachweis untersucht. Auch die derzeit vorherrschende Auffassung, dass Patienten mit MuSK-Antikörpernachweis nicht von einer Thx profitieren, wird auf Basis der widersprüchlichen Daten neu geprüft werden müssen. Aus chirurgischer Sicht wird auf Basis des in der MGTX-Studie eingesetzten Thx-Verfahrens der komplett-erweiterten medianen Sternotomie momentan der Stellenwert der minimalinvasiven thorakoskopischen Verfahren als schonende Alternative geprüft. Für die weitere Ausdifferenzierung der Thx-Verfahren wären aus klinisch-wissenschaftlicher Sicht randomisiert-kontrollierte Studien im Vergleich zum offenen Thx-Verfahren wünschenswert. Schon jetzt gelingt es jedoch unter Anwendung der Roboterassistenz, alle Ansprüche an die Thx aus chirurgischer, klinisch-neurologischer sowie Patientensicht optimal zu erfüllen. Aufgrund ethischer Aspekte werden daher andere Wege des wissenschaftlichen Vergleichs der verschiedenen Operationsverfahren in den Mittelpunkt rücken.

Abstract

Over recent years, investigations into the pathophysiology of myasthenia gravis (MG) have made great progress, resulting in characterization of subgroups, and extension of multimodal treatment approaches. This applies especially to the role of thymectomy (Thx). For thymoma-associated MG, Thx is always indicated. Furthermore, based on large cohort studies over decades, Thx has also become a central part of immune-modulating therapy in MG patients without thymoma. The lack of randomized studies, however, caused persistent uncertainty regarding the significance of Thx. The MGTX study has clearly shown the effectiveness of Thx. Particularly in the acquired early onset MG (EOMG), complete resection of all thymic tissue resulted in significant improvement in myasthenic complaints and reduction in immunosuppressive medication. Because the MGTX study only included patients younger than 65 years with generalized MG who were positive for acetylcholine-receptor antibodies, at present the significance of Thx for other relevant subgroups such as those with juvenile MG or ocular MG, older MG patients, as well as seronegative patients is under investigation. Even the prevailing opinion of no benefit of Thx for MuSK-positive patients probably needs reevaluation because of equivocal findings. With respect to surgery, the value of thoracoscopic modifications for Thx as a minimally-invasive alternative to extended median sternotomy for MG employed in the MGTX study is currently being evaluated. For clinical-scientific reasons, randomized comparative studies would be required for further assessment of different minimally-invasive Thx-techniques as compared to the conventional open procedures. Currently, however, robot-assisted thoracoscopic unilateral approach for Thx by an experienced surgeon meets all requirements related to surgical, clinical-neurological, and patient-related aspects. Ethical aspects, therefore, will become more important with regard to the comparison of different operation techniques.

 
  • Literatur

  • 1 Wolfe GI, Kaminski HJ, Aban IB. et al. Randomized trial of thymectomy in myasthenia gravis. N Engl J Med 2016; 375: 511-522
  • 2 Schumacher ED, Roth J. Thymektomie bei einem Fall von Morbus Basedowi mit Myasthenie. Mitt Grenzgeb Med Chir 1912; 25: 746-765
  • 3 Laqueur L, Weigert C. Beiträge zur Lehre von der Erbʼschen Krankheit. Neurol Zbl 1901; 20: 4
  • 4 Blalock A, Mason MF, Morgan HJ. et al. Myasthenia Gravis and Tumors of the Thymic Region: Report of a Case in Which the Tumor Was Removed. Ann Surg 1939; 110: 544-561
  • 5 Blalock A. Thymectomy in the treatment of myasthenia: report of 20 cases. J Thorac Surg 1944; 13: 316-336
  • 6 Blalock A, McGehee H, Ford FR. et al. The treatment of myasthenia gravis (by) removal of the thymus gland: preliminary report. JAMA 1941; 117: 1529-1533
  • 7 Vincent A, Palace J, Hilton-Jones D. Myasthenia gravis. Lancet 2001; 357: 2122-2128
  • 8 Gilhus NE, Verschuuren JJ. Myasthenia gravis: subgroup classification and therapeutic strategies. Lancet Neurol 2015; 14: 1023-1036
  • 9 Sieb JP. Myasthenia gravis: an update for the clinician. Clin Exp Immunol 2013; 175: 10
  • 10 Keynes G. The results of thymectomy in myasthenia gravis. Br Med J 1949; 2: 611-616
  • 11 Shrager JB, Nathan D, Brinster CJ. et al. Outcomes after 151 extended transcervical thymectomies for myasthenia gravis. Ann Thorac Surg 2006; 82: 1863-1869
  • 12 Jaretzki 3rd A, Penn AS, Younger DS. et al. “Maximal” thymectomy for myasthenia gravis. Results. J Thorac Cardiovasc Surg 1988; 95: 747-757
  • 13 Jaretzki 3rd A. Video-assisted thoracoscopic extended thymectomy and extended transsternal thymectomy in non-thymomatous myasthenia gravis patients. J Neurol Sci 2004; 217: 233-234 ; author reply 235-236.
  • 14 Tomulescu V, Sgarbura O, Stanescu C. et al. Ten-year results of thoracoscopic unilateral extended thymectomy performed in nonthymomatous myasthenia gravis. Ann Surg 2011; 254: 761-765 ; discussion 765–766.
  • 15 Bulkley GB, Bass KN, Stephenson GR. et al. Extended cervicomediastinal thymectomy in the integrated management of myasthenia gravis. Ann Surg 1997; 226: 324-334 ; discussion 334-325.
  • 16 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
  • 17 Sieb JP. Myasthenia gravis: an update for the clinician. Clin Exp Immunol 2014; 175: 408-418
  • 18 Sonett JR, Magee MJ, Gorenstein L. Thymectomy and myasthenia gravis: a history of surgical passion and scientific excellence. J Thorac Cardiovasc Surg 2017; 154: 306-309
  • 19 Kark AE, Kirschner PA. Total thymectomy by the transcervical approach. Br J Surg 1971; 58: 321-326
  • 20 Cooper JD, Al-Jilaihawa AN, Pearson FG. et al. An improved technique to facilitate transcervical thymectomy for myasthenia gravis. Ann Thorac Surg 1988; 45: 242-247
  • 21 Jaretzki 3rd A. Thymectomy for myasthenia gravis: analysis of the controversies regarding technique and results. Neurology 1997; 48 (Suppl. 05) 52S-63S doi: https://doi.org/10.1212/WNL.48.Suppl_5.52S
  • 22 Hermes HM, Cohen GA, Mehrotra AK. et al. Association of thymectomy with infection following congenital heart surgery. World J Pediatr Congenit Heart Surg 2011; 2: 351-358
  • 23 Gui M, Luo X, Lin J. et al. Long-term outcome of 424 childhood-onset myasthenia gravis patients. J Neurol 2015; 262: 823-830
  • 24 Madenci AL, Li GZ, Weil BR. et al. The role of thymectomy in the treatment of juvenile myasthenia gravis: a systematic review. Pediatr Surg Int 2017; 33: 683-694
  • 25 Della Marina A, Kolbel H, Mullers M. et al. Outcome after robotic-assisted thymectomy in children and adolescents with acetylcholine receptor antibody-positive juvenile myasthenia gravis. Neuropediatrics 2017; 48: 315-322
  • 26 Binks S, Vincent A, Palace J. Myasthenia gravis: a clinical-immunological update. J Neurol 2016; 263: 826-834
  • 27 Kawaguchi N, Kuwabara S, Nemoto Y. et al. Effects of thymectomy on late-onset myasthenia gravis without thymoma. Clin Neurol Neurosurg 2007; 109: 858-861
  • 28 Skeie GO, Apostolski S, Evoli A. et al. Guidelines for treatment of autoimmune neuromuscular transmission disorders. Eur J Neurol 2010; 17: 893-902
  • 29 Grob D, Brunner N, Namba T. et al. Lifetime course of myasthenia gravis. Muscle Nerve 2008; 37: 141-149
  • 30 Schumm F, Dichgans J. [Clinical evaluation system (score) of ocular symptoms in myasthenia gravis]. Nervenarzt 1985; 56: 186-187
  • 31 Tansel T, Onursal E, Barlas S. et al. Results of surgical treatment for nonthymomatous myasthenia gravis. Surg Today 2003; 33: 666-670
  • 32 Luo LQ, Zhang JZ, Cui HN. Clinical analysis of thymectomy for juvenile with myasthenia gravis. China J Mod Med 2008; 15: 2
  • 33 Xie SP, Huang J. A clinical assessment of thymectomy for the treatment of ocular myasthenia gravis in children. J Clin Surg 2010; 18 DOI: 10.3969/j.issn.1005-6483.2010.01.016.
  • 34 Lui Z, Feng H, Yeung SC. et al. Extended transsternal thymectomy for the treatment of ocular myasthenia gravis. Ann Thorac Surg 2011; 92: 7
  • 35 Zhu K, Li J, Huang X. et al. Thymectomy is a beneficial therapy for patients with non-thymomatous ocular myasthenia gravis: a systematic review and meta-analysis. Neurol Sci 2017; 38: 1753-1760
  • 36 Lauriola L, Ranelletti F, Maggiano N. et al. Thymus changes in anti-MuSK-positive and -negative myasthenia gravis. Neurology 2005; 64: 536-538
  • 37 Leite MI, Strobel P, Jones M. et al. Fewer thymic changes in MuSK antibody-positive than in MuSK antibody-negative MG. Ann Neurol 2005; 57: 444-448
  • 38 Ponseti JM, Caritg N, Gamez J. et al. 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
  • 39 Gilhus NE, Skeie GO, Romi F. et al. Myasthenia gravis – autoantibody characteristics and their implications for therapy. Nat Rev Neurol 2016; 12: 259-268
  • 40 Wright CD. Management of thymomas. Crit Rev Oncol Hematol 2008; 65: 109-120
  • 41 Marulli G, Rea F, Melfi F. et al. Robot-aided thoracoscopic thymectomy for early-stage thymoma: a multicenter European study. J Thorac Cardiovasc Surg 2012; 144: 1125-1130
  • 42 Marulli G, Maessen J, Melfi F. et al. Multi-institutional European experience of robotic thymectomy for thymoma. Ann Cardiothorac Surg 2016; 5: 18-25
  • 43 Fukuhara M, Higuchi M, Owada Y. et al. Clinical and pathological aspects of microscopic thymoma with myasthenia gravis and review of published reports. J Thorac Dis 2017; 9: 1592-1597
  • 44 Keijzers M, Dingemans AM, Blaauwgeers H. et al. 8 yearsʼ experience with robotic thymectomy for thymomas. Surg Endosc 2014; 28: 1202-1208
  • 45 Kang CH, Hwang Y, Lee HJ. et al. Robotic thymectomy in anterior mediastinal mass: propensity score matching study with transsternal thymectomy. Ann Thorac Surg 2016; 102: 895-901
  • 46 Kneuertz PJ, Kamel MK, Stiles BM. et al. Robotic thymectomy is feasible for large thymomas: a propensity-matched comparison. Ann Thorac Surg 2017; 104: 1673-1678
  • 47 Liu XD, Shao MR, Sun L. et al. Influence of body mass index on postoperative complications after thymectomy in myasthenia gravis patients. 2017 www.impactjournals.com/oncotarget/
  • 48 Gellert K. Die thorakoskopische Thymektomie. Akt Neurol 1998; 25: S70-S72
  • 49 Ruckert JC, Gellert K, Einhaupl K. et al. [Thoracoscopic thymectomy for treatment of myasthenia gravis]. Zentralbl Chir 1998; 123: 506-511
  • 50 Mineo TC, Pompeo E, Ambrogi V. et al. Adjuvant pneumomediastinum in thoracoscopic thymectomy for myasthenia gravis. Ann Thorac Surg 1996; 62: 1210-1212
  • 51 Ruckert JC, Gellert K, Muller JM. Operative technique for thoracoscopic thymectomy. Surg Endosc 1999; 13: 943-946
  • 52 Landreneau RJ, Dowling RD, Castillo WM. et al. Thoracoscopic resection of an anterior mediastinal tumor. Ann Thorac Surg 1992; 54: 142-144
  • 53 Mack MJ, Landreneau RJ, Yim AP. et al. Results of video-assisted thymectomy in patients with myasthenia gravis. J Thorac Cardiovasc Surg 1996; 112: 1352-1359 ; discussion 1359–1360
  • 54 Brenna G, Antozzi C, Montomoli C. et al. A propensity score analysis for comparison of T-3b and VATET in myasthenia gravis. Neurology 2017; 89: 189-195
  • 55 Ruckert JC, Ismail M, Badakhshi H. et al. [Thymectomy in myasthenia and/or thymoma]. Zentralbl Chir 2014; 139: 121-132 ; quiz 133–124
  • 56 Ismail M, Swierzy M, Ruckert JC. State of the art of robotic thymectomy. World J Surg 2013; 37: 2740-2746
  • 57 Ismail M, Swierzy M, Ruckert RI. et al. Robotic thymectomy for myasthenia gravis. Thorac Surg Clin 2014; 24: 189-195 , vi-vii
  • 58 Marulli G, Schiavon M, Perissinotto E. et al. Surgical and neurologic outcomes after robotic thymectomy in 100 consecutive patients with myasthenia gravis. J Thorac Cardiovasc Surg 2013; 145: 730-735 ; discussion 735–736
  • 59 Ruckert JC, Swierzy M, Ismail M. Comparison of robotic and nonrobotic thoracoscopic thymectomy: a cohort study. J Thorac Cardiovasc Surg 2011; 141: 673-677
  • 60 Kawaguchi K, Fukui T, Nakamura S. et al. A bilateral approach to extended thymectomy using the da Vinci Surgical System for patients with myasthenia gravis. Surg Today 2018; 48: 195-199
  • 61 Rückert JC, Swierzy M, Rückert RI. et al. Thymectomy (VATS, da Vinci). In: Dienemann HC, Hoffmann H, Detterbeck FC. , ed. Chest Surgery: Springer Surgery Atlas Series. Springer; 2014
  • 62 Ismail M, Swierzy M, Rückert RI. et al. Robotic thymectomy for myasthenia gravis. Thorac Surg Clin 2014; 24: 189-195
  • 63 Elsayed HH, Gamal M, Raslan S. et al. Video-assisted thoracoscopic thymectomy for non-thymomatous myasthenia gravis: a right-sided or left-sided approach?. Interact Cardiovasc Thorac Surg 2017; 25: 651-653