Thymectomy for Non-thymomatous Myasthenia Gravis

  • Joshua R. Sonett
  • Bianca Bromberger
  • Alfred JaretzkiIII
Part of the Current Clinical Neurology book series (CCNEU)


The recent publication of the first randomized trial of thymectomy versus medical management alone provides the first class I evidence in support of the use of thymectomy in the treatment of non-thymomatous myasthenia gravis. However, many questions remain, including patient selection, its efficacy for different subtypes of MG, timing of surgery, and optimal resection technique. This chapter will provide an overview of the surgical anatomy of the thymus and the various surgical approaches to thymectomy. The available evidence regarding the effect of thymectomy in non-thymomatous MG is reviewed, and recommendations regarding optimal timing, patient selection, and considerations for its role in the different subtypes of MG will be addressed. After a review of the issues surrounding research on thymectomy in MG, a summary of available outcome data of the various resection techniques is provided in addition to limited recommendations regarding the surgical approach of choice. A discussion of perioperative considerations for patient management is included, and recommendations are provided for future research into the surgical management of non-thymomatous MG.


Thymectomy Myasthenia gravis Non-thymomatous Thymus Video-assisted thoracoscopy Thoracoscopic thymectomy Videoscopic thymectomy Robotic thymectomy VATS Transcervical thymectomy Transsternal thymectomy 


  1. 1.
    Wolfe GI, Kaminski HJ, Aban IB, Minisman G, Kuo H-C, Marx A, et al. Randomized trial of thymectomy in myasthenia gravis. N Engl J Med. 2016;375:511–22.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Blalock A, Harvey AM, Ford FF, Lilienthal J Jr. The treatment of myasthenia gravis by removal of the thymus gland. JAMA. 1941;117:1529–33.CrossRefGoogle Scholar
  3. 3.
    Keynes G. The surgery of the thymus gland. Br J Surg. 1946;32:201–14.CrossRefGoogle Scholar
  4. 4.
    Kirschner PA, Osserman KE, Kark AE. Studies in myasthenia gravis: transcervical total thymectomy. JAMA. 1969;209:906–10.PubMedCrossRefGoogle Scholar
  5. 5.
    Kark AE, Kirschner PA. Total thymectomy by the transcervical approach. Br J Surg. 1971;56:321–6.CrossRefGoogle Scholar
  6. 6.
    Faulkner SL, Ehyai AS, Fisher RD, Fenichel GM, Bender HW. Contemporary management of myasthenia gravis: the clinical role of thymectomy. Ann Thorac Surg. 1977;23:348–52.PubMedCrossRefGoogle Scholar
  7. 7.
    Olanow CW, Wechsler AS, Roses AD. A prospective study of thymectomy and serum acetylcholine receptor antibodies in myasthenia gravis. Ann Surg. 1982;196:113–21.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Vincent A, Newsom-Davis J, Newton P, Beck N. Acetylcholine receptor antibody and clinical response to thymectomy in myasthenia gravis. Neurology. 1983;33:1276–82.PubMedCrossRefGoogle Scholar
  9. 9.
    Hankins JR, Mayer RF, Satterfield JR, Turney SZ, Attar A, Sequeira AJ, et al. Thymectomy for myasthenia gravis: 14 year experience. Ann Surg. 1985;201:618–25.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Otto TJ, Strugalska H. Surgical treatment for myasthenia gravis. Thorax. 1987;42:199–204.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Cooper J, Jaretzki A III, Mulder DG, Papatestas AS. Symposium: thymectomy for myasthenia gravis. Contemp Surg. 1989;34:65–86.Google Scholar
  12. 12.
    Papatestas AE, Cooper J, Jaretzki A III, Mulder DG. Symposium: thymectomy for myasthenia gravis. Contemp Surg. 1989;34:65–85.Google Scholar
  13. 13.
    Verma P, Oger J. Treatment of acquired autoimmune myasthenia gravis: a topic review. Can J Neurol Sci. 1992;19:360–75.PubMedGoogle Scholar
  14. 14.
    Drachman DB. Myasthenia gravis. N Engl J Med. 1994;330:1797–810.PubMedCrossRefGoogle Scholar
  15. 15.
    Penn AS. Thymectomy for myasthenia gravis. In: Lisak RP, editor. Handbook of myasthenia gravis and myasthenic syndromes. New York: Marcel Dekker, Inc; 1994. p. 21–339.Google Scholar
  16. 16.
    Mack MJ, Landreneau RD, Yim AP, Hazelrigg SR, Scruggs GR. Results of video-assisted thymectomy in patients with myasthenia gravis. J Thor Cardiovasc Surg. 1996;112:1352–60.CrossRefGoogle Scholar
  17. 17.
    Penn AS, Jaretzki A III, Wolff M, Chang HW, Tennyson V. Thymic abnormalities: antigen or antibody? Response to thymectomy in myasthenia gravis. Ann NY Acad Sci. 1981;377:786–803.PubMedCrossRefGoogle Scholar
  18. 18.
    Wekerle H, Muller-Hermelink HK. The thymus in myasthenia gravis. Curr Top Pathol. 1986;75:179–206.PubMedCrossRefGoogle Scholar
  19. 19.
    Younger DS, Worrall BB, Penn AS. Myasthenia gravis: historical perspective and overview. Neurology. 1997;48(Suppl 5):1–7.CrossRefGoogle Scholar
  20. 20.
    Hohlfeld R, Wekerle H. Reflections on the “intrathymic pathogenesis” of myasthenia gravis. J Neuroimmunol. 2008;201–202:21–7.PubMedCrossRefGoogle Scholar
  21. 21.
    Lauriola L, Ranelletti F, Maggiano N, Guerriero M, Punzi C, Marsili F, et al. Thymus changes in anti-MuSK-positive and -negative myasthenia gravis. Neurology. 2005;64:536–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Penn AS, Lovelace RE, Lange DJ, Toufexis G, Brockbank K. Experimental myasthenia gravis in neonatally thymectomized rabbits. Neurology. 1977;27:365.Google Scholar
  23. 23.
    Masaoka A, Monden Y, Seike Y, Tanioka T, Kagotani K. Reoperation after transcervical thymectomy for myasthenia gravis. Neurology. 1982;32:83–5.PubMedCrossRefGoogle Scholar
  24. 24.
    Rosenberg M, Jauregui WO, Vega MED, Herrera MR, Roncoroni AJ. Recurrence of thymic hyperplasia after thymectomy in myasthenia gravis: its importance as a cause of failure of surgical treatment. Am J Med. 1983;74:78–82.PubMedCrossRefGoogle Scholar
  25. 25.
    Henze A, Biberfeld P, Christensson B, Matell G, Pirskanen R. Failing transcervical thymectomy in myasthenia gravis: an evaluation of transsternal re-exploration. Scand J Thor Cardiovasc Surg. 1984;18:235–8.CrossRefGoogle Scholar
  26. 26.
    Rosenberg M, Jauregui WO, Herrera MR, Roncoroni A, Rojas OR, Olmedo GSM. Recurrence of thymic hyperplasia after trans-sternal thymectomy in myasthenia gravis. Chest. 1986;89:888–91.PubMedCrossRefGoogle Scholar
  27. 27.
    Jaretzki A III, Penn AS, Younger DS, Wolff M, Olarte MR, Lovelace RE, et al. “Maximal” thymectomy for myasthenia gravis: results. J Thorac Cardiovasc Surg. 1988;95:747–57.PubMedGoogle Scholar
  28. 28.
    Miller RG, Filler-Katz A, Kiprov D, Roan R. Repeat thymectomy in chronic refractory myasthenia gravis. Neurology. 1991;41:923–4.PubMedCrossRefGoogle Scholar
  29. 29.
    Kornfeld P, Merav A, Fox S, Maier K. How reliable are imaging procedures in detecting residual thymus after previous thymectomy. Ann NY Acad Sci. 1993;681:575–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Monden MAY. Comparison of the results of transsternal simple, transcervical simple and extended thymectomy. Ann NY Acad Sci. 1981;377:755–64.PubMedCrossRefGoogle Scholar
  31. 31.
    Matell G, Lebram G, Osterman PO, Pirskanen R. Follow up comparison of suprasternal vs transsternal method for thymectomy in myasthenia gravis. Ann NY Acad Sci. 1981;377:844–5.CrossRefGoogle Scholar
  32. 32.
    Masaoka A, Nagaoka Y, Kotake Y. Distribution of thymic tissue at the anterior mediastinum: current procedures in thymectomy. J Thorac Cardiovasc Surg. 1975;70:747–54.PubMedGoogle Scholar
  33. 33.
    Jaretzki A III, Wolff M. “Maximal” thymectomy for myasthenia gravis: surgical anatomy and operative technique. J Thorac Cardiovasc Surg. 1988;96:711–6.PubMedGoogle Scholar
  34. 34.
    Fukai I, Funato Y, Mizuno Y, Hashimoto T, Masaoka A. Distribution of thymic tissue in the mediastinal adipose tissue. J Thorac Cardiovasc Surg. 1991;101:1099–102.PubMedGoogle Scholar
  35. 35.
    Jaretzki A III, Barohn RJ, Ernstoff RM, Kaminski HJ, Keesey JC, Penn AS, et al. Myasthenia gravis: recommendations for clinical research standards. Neurology. 2000;55:16–23.PubMedCrossRefGoogle Scholar
  36. 36.
    Sonett JR, Jaretzki A III. Thymectomy for nonthymomatous myasthenia gravis: a critical analysis. Ann N Y Acad Sci. 2008;1132:315–28.PubMedCrossRefGoogle Scholar
  37. 37.
    Jaretzki A III. Thymectomy for myasthenia gravis: an analysis of the controversies regarding technique and results. Neurology. 1997;48:52–63.CrossRefGoogle Scholar
  38. 38.
    Bulkley GB, Bass KN, Stephenson R, Diener-West M, George S, Reilly PA, et al. Extended cervicomediastinal thymectomy in the integrated management of myasthenia gravis. Ann Surg. 1997;226:324–35.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Anastasiadis K, Ratnatunga C. Thymectomy. In: Anastasiadis K, Ratnatunga C, editors. The thymus gland: diagnosis and surgical management. Berlin: Springer; 2007. p. 63–83.Google Scholar
  40. 40.
    Sonett JR, Jaretzki A III. Transcervical-transsternal maximal thymectomy for myasthenia gravis. In: Shields TW, LoCicero III J, Reed CE, Feins RH, editors. General thoracic surgery. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2009. p. 2306–11.Google Scholar
  41. 41.
    Clark RE, Marbarger JP, West PN, Sprat JA, Florence JM, Roper CL, Ferguson TB, et al. Thymectomy for myasthenia gravis in the young adult. Long-term results. J Thorac Cardiovasc Surg. 1980;80:696–701.PubMedGoogle Scholar
  42. 42.
    Blalock A, Mason MF, Morgan HJ, Riven SS. Myasthenia gravis and tumors of the thymus region: report of a case in which the tumor was removed. Am Surg. 1939;110:544–61.Google Scholar
  43. 43.
    Clagett OT, Eaton LM. Surgical treatment of myasthenia gravis. J Thorac Surg. 1947;16:62–80.PubMedGoogle Scholar
  44. 44.
    Blalock A. Thymectomy in the treatment of myasthenia gravis: report of 20 cases. J Thorac Surg. 1944;13:1291–308.Google Scholar
  45. 45.
    Nichols FC, Trastek VF. Standard thymectomy. In: Shields TW, LoCicero III J, Reed CE, Feins RH, editors. General thoracic surgery. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2009. p. 2278–82.Google Scholar
  46. 46.
    LoCicero J III. The combined cervical and partial sternotomy approach for thymectomy. Chest Surg Clin N Am. 1996;6:85–93.PubMedGoogle Scholar
  47. 47.
    Trastek VF. Thymectomy. In: Kaiser LR, Krin IL, Spray TL, editors. Mastery of cardiothoracic surgery. Philadelphia: Lippincott-Raven; 1998. p. 105–11.Google Scholar
  48. 48.
    deCampos JRM, Filomeno LTB, Marchiori PE, Jatene FB. Partial sternotomy approach to the thymus. In: Yim AP, Hazelrigg SR, Izzat B, Landreneau RJ, Mack MJ, Naunheim KS, editors. Minimally access cardiothoracic surgery. Philadelphia: WB Saunders; 1999. p. 205–8.Google Scholar
  49. 49.
    Masaoka A, Yamakawa Y, Niwa H, Fukai I, Condo S, Kobayashi M, et al. Extended thymectomy for myasthenia gravis: a 20 year review. Ann Thor Surg. 1996;62:853–9.CrossRefGoogle Scholar
  50. 50.
    Zieliński M, Kuzdzal 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.PubMedCrossRefGoogle Scholar
  51. 51.
    Mulder DG. Extended transsternal thymectomy. Chest Surg Clin N Am. 1996;6:95–105.PubMedGoogle Scholar
  52. 52.
    Masaoka A. Extended transsternal thymectomy. In: Shields TW, LoCicero III J, Reed CE, Feins RH, editors. General thoracic surgery. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2009. p. 2298–304.Google Scholar
  53. 53.
    Fischer JE, Grinvalski HT, Nussbaum MS, Sayers HK, Cole RE, Samaha FJ. Aggressive surgical approach for drug-free remission from myasthenia gravis. Ann Surg. 1987;205:496–503.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Hatton P, Diehl J, Daly BDT, Rheinlander HF, Johnson H, Shrader JB, et al. Transternal radical thymectomy for myasthenia gravis: a 15-year review. Ann Thorac Surg. 1989;47:838–40.PubMedCrossRefGoogle Scholar
  55. 55.
    Mulder DM. Extended transsternal thymectomy. In: Shields TW, LoCicero III J, Reed CE, Feins RH, editors. General thoracic surgery. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2009. p. 2233–7.Google Scholar
  56. 56.
    Kark AE, Papatestas AE. Some anatomic features of the transcervical approach for thymectomy. Mt Sinai J Med. 1971;38:580–4.PubMedGoogle Scholar
  57. 57.
    Papatestas AE, Genkins G, Kornfeld P, Horowitz S, Kark AE. Transcervical thymectomy in myasthenia gravis. Surg Gynecol Obst. 1975;140:535–40.Google Scholar
  58. 58.
    Cooper J, Al-Jilaihawa A, Pearson F, Humphrey J, Humphrey HE. An improved technique to facilitate transcervical thymectomy for myasthenia gravis. Ann Thorac Surg. 1988;45:242–7.PubMedCrossRefGoogle Scholar
  59. 59.
    Bril V, Kojic S, Ilse W, Cooper J. Long-term clinical outcome after transcervical thymectomy for myasthenia gravis. Ann Thorac Surg. 1998;65:1520–2.PubMedCrossRefGoogle Scholar
  60. 60.
    Shrager JB, Deeb ME, Mick R, Brinster CJ, Childers HE, Marshall MB, et al. Transcervical thymectomy for myasthenia gravis achieves results comparable to thymectomy by sternotomy. Ann Thorac Surg. 2002;74:320–7.PubMedCrossRefGoogle Scholar
  61. 61.
    Maggi G, Cristofori RC, Marzio PD, Pernazza F, Turello D, Ruffini E. Transcervical thymectomy with partial sternal split. Osp Ital Chir. 2004;10:53–60.Google Scholar
  62. 62.
    dePerrot M, Bril V, McRae K, Keshavjee S. Impact of minimally invasive trans-cervical thymectomy on outcome in patients with myasthenia gravis. Eur J Cardiothoracic Surg. 2003;24:677–83.CrossRefGoogle Scholar
  63. 63.
    Bramis J, Diamantis T, Tsigris C, Pikoulis E, Papaconstaninou I, Nikolaou A, et al. Video-assisted transcervical thymectomy. Surg Endosc. 2004;18:1535–8.PubMedCrossRefGoogle Scholar
  64. 64.
    Zielinski M, Kuzdzal J, Szlubowski A, Soja J. Transcervical-subxiphoid-video thoracoscopic “maximal” thymectomy—operative technique and early results. Ann Thorac Surg. 2004;78:399–403.CrossRefGoogle Scholar
  65. 65.
    Sugarbaker DJ. Thoracoscopy in the management of anterior mediastinal masses. Ann Thor Surg. 1993;56:653–6.CrossRefGoogle Scholar
  66. 66.
    Roviaro G, Rebuffat C, Varoli F, Vergani C, Maciocco M, Scalambra SM. Videothoracoscopic excision of mediastinal masses: indications and technique. Ann Thorac Surg. 1994;58:1679–84.PubMedCrossRefGoogle Scholar
  67. 67.
    Sabbagh MN, Garza JJS, Patten B. Thoracoscopic thymectomy in patients with myasthenia gravis. Muscle Nerve. 1995;18:1475–7.PubMedCrossRefGoogle Scholar
  68. 68.
    Yim APC, Kay RLC, Ho JKS. Video-assisted thoracoscopic thymectomy for myasthenia gravis. Chest. 1995;108:1440–3.PubMedCrossRefGoogle Scholar
  69. 69.
    Magee MJ, Mack MJ. Video-assisted thymectomy. In: Shields TW, LoCicero III J, Reed CE, Feins RH, editors. General thoracic surgery. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2009. p. 2294–5.Google Scholar
  70. 70.
    Novellino L, Longoni M, Spinelli L, Andretta M, Cozzi M, Faillace G, et al. “Extended” thymectomy, without sternotomy, performed by cervicotomy and thoracoscopic technique in the treatment of myasthenia gravis. Int Surg. 1994;79:378–81.PubMedGoogle Scholar
  71. 71.
    Scelsi R, Ferro MT, Scelsi L, Novellino L, Mantegazza R, Cornelio F, et al. Detection and morphology of thymic remnants after video-assisted thoracoscopic thymectomy (VATET) in patients with myasthenia gravis. Int Surg. 1996;81:14–7.PubMedGoogle Scholar
  72. 72.
    Shiono H, Ohta M, Okumura M. Open video-assisted techniques: thoracoscopic extended thymectomy with bilateral approach and anterior chest wall lifting. In: Lavini C, Moran CA, Morandi U, Schoenhuber R, editors. Thymus gland pathology. Milan: Springer; 2008. p. 187–94.CrossRefGoogle Scholar
  73. 73.
    Chang PC, Chou SH, Kao EL, Cheng YJ, Chuang HY, Liu CK, et al. Bilateral video-assisted thoracoscopic thymectomy vs. extended transsternal thymectomy in myasthenia gravis: a prospective study. Eur Surg Res. 2005;37:199–203.PubMedCrossRefGoogle Scholar
  74. 74.
    Lee CY, Kim DJ, Lee JG, Park IK, Bae MK, Chung KY. Bilateral video-assisted thoracoscopic thymectomy has a surgical extent similar to that of transsternal extended thymectomy with more favorable early surgical outcomes for myasthenia gravis patients. Surg Endosc. 2011;25:849–54.PubMedCrossRefGoogle Scholar
  75. 75.
    Shigemura N, Shiono H, Inour M, Minami M, Ochta M, Okumura M, et al. Inclusion of the transcervical approach in video-assisted thoracoscopic extended thymectomy (VATET) for myasthenia gravis: a prospective trial. Surg Endosc. 2006;20:1614–8.PubMedCrossRefGoogle Scholar
  76. 76.
    Morgan JA, Ginsburg ME, Sonett JR, Morales DLS, Kohmoto T, Gorenstein LA, et al. Advanced thoracoscopic procedures are facilitated by computer aided robotic technology. Eur J Cardiothoracic Surg. 2003;23:883–7.CrossRefGoogle Scholar
  77. 77.
    Ashton RC, McGinnis KM, Connery CP, Swistel DS, Ewing DR, DeRose JJ. Total endoscopic robotic thymectomy for myasthenia gravis (case report). Ann Thorac Surg. 2003;75:569–71.PubMedCrossRefGoogle Scholar
  78. 78.
    Rea F, Marulli G, Bortolotti L, Feltracco P, Zuin A, Sartori F. Experience with the “Da Vinci” robotic system for thymectomy in patients with myasthenia gravis: report of 33 cases. Ann Thorac Surg. 2006;81:455–9.PubMedCrossRefGoogle Scholar
  79. 79.
    Marulli G, Schiavon M, Perissinotto E, Bugana A, Di Chiara F, Rebusso A, et al. Surgical and neurologic outcomes after robotic thymectomy in 100 consecutive patients with myasthenia gravis. J Thorac Cardiovasc Surg. 2013;145:730–5.PubMedCrossRefGoogle Scholar
  80. 80.
    Melfi FM, Fanucchi O, Mussi A. Minimally invasive mediastinal surgery. Ann Cardiothorac Surg. 2016;5:10–7.PubMedPubMedCentralGoogle Scholar
  81. 81.
    Hsu CP, Chuang CY, Hsu NY, Chen CY. Comparison between the right side and subxiphoid bilateral approaches in performing video-assisted thoracoscopic extended thymectomy for myasthenia gravis. Surg Endosc. 2004;18:821–4.PubMedCrossRefGoogle Scholar
  82. 82.
    Uchiyama A, Shimizu S, Murai H, Kuroki S, Okido M, Tanaka M. Infrasternal mediastinoscopy thymectomy in myasthenia gravis: surgical results in 23 patients. Ann Thor Surg. 2001;72:1902–5.CrossRefGoogle Scholar
  83. 83.
    Suda T, Sugimura H, Tochii D, Kihara M, Hattori Y. Single-port thymectomy through an infrasternal approach. Ann Thor Surg. 2012;93:334–6.CrossRefGoogle Scholar
  84. 84.
    Hsu CP, Chuang CY, Hsu NY, Shia SE. Subxiphoid approach for video-assisted thoracoscopic extended thymectomy in treating myasthenia gravis. Interact Cardiovasc Thorac Surg. 2002;1:4–8.PubMedCrossRefGoogle Scholar
  85. 85.
    Suda T, Tochii D, Tochii S, Takagi Y. Trans-subxiphoid robotic thymectomy. Interact Cardiovasc Thorac Surg. 2015;20:669–71.PubMedCrossRefGoogle Scholar
  86. 86.
    Suda T, Kaneda S, Hachimaru A, Tochii D, Maeda R, Tochii S, et al. Thymectomy via a subxiphoid approach: single-port and robot-assisted. J Thorac Dis. 2016;8(Suppl 3):265–71.Google Scholar
  87. 87.
    Benatar M, Sanders DB, Burns TM, Cutter GR, Guptill JT, Baggi F, et al.; Task Force on MG Study Design of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Recommendations for myasthenia gravis clinical trials. Muscle Nerve. 2012;45:909–17.Google Scholar
  88. 88.
    Weinberg A, Gelijns A, Moskowitz A, Jaretzki A III. Myasthenia gravis: outcomes analysis. 2000.
  89. 89.
    McQuillen MP, Leone MG. A treatment carol: thymectomy revisited. Neurology. 1977;1277:1103–6.CrossRefGoogle Scholar
  90. 90.
    Viet HR, Schwab RS. Thymectomy for myasthenia gravis. In: Veit HR, editor. Records of experience of Mass Gen Hosp. Springfield: Charles C Thomas; 1960. p. 597–607.Google Scholar
  91. 91.
    Oosterhuis HJ. Observations of the natural history of myasthenia gravis and the effect of thymectomy. Ann NY Acad Sci. 1981;377:678–90.PubMedCrossRefGoogle Scholar
  92. 92.
    Lawless JF. Life tables, graphs, and related procedures. In: Lawless JF, editor. Statistical models and methods for life table data. New York: Wiley; 1982. p. 52–94.Google Scholar
  93. 93.
    Durelli L, Maggi G, Casadio C, Ferri R, Rendine S, Bergamini L. Actuarial analysis of the occurrence of remission following thymectomy for myasthenia gravis in 400 patients. J Neurol Neurosurg Psychiatry. 1991;54:406–11.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Olak J, Chiu RCJ. A surgeon’s guide to biostatistical inferences. Part II. ACS Bull. 1993;78:27–31.Google Scholar
  95. 95.
    Blackstone EH. Outcome analysis using hazard function methodology. Ann Thorac Surg. 1996;61(Suppl 2):2–7.CrossRefGoogle Scholar
  96. 96.
    Sanders DB, Kaminski HJ, Jaretzki A III, Phillips LH II. Thymectomy for myasthenia gravis in older patients. J Am Coll Surg. 2001;193:340–1.PubMedCrossRefGoogle Scholar
  97. 97.
    Wolfe GI, Kaminski HJ, Sonett JR, Aban IB, Kuo H, Cutter GR. Randomized trial of thymectomy in myasthenia gravis. J Thorac Dis. 2016;8:1782–3.CrossRefGoogle Scholar
  98. 98.
    Diaz A, Black E, Dunning J. Is thymectomy in non-thymomatous myasthenia gravis of any benefit? Interact Cardiovasc Thorac Surg. 2014;18:381–9.PubMedCrossRefGoogle Scholar
  99. 99.
    Taioli E, Paschal PK, Liu B, Kaufman AJ, Flores RM. Comparison of conservative treatment and thymectomy on myasthenia gravis outcome. Ann Thorac Surg. 2016;102:1805–13.PubMedCrossRefGoogle Scholar
  100. 100.
    Sanders DB, Wolfe GI, Benatar M, Evoli A, Gilhus NE, Illa I, et al. International consensus guidance for management of myasthenia gravis: executive summary. Neurology. 2016;87:419–25.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Skeie GO, Apostolski S, Evoli A, Gilhus NE, Illa I, Harms L, et al.; European Federation of Neurological Societies. Guidelines for treatment of autoimmune neuromuscular transmission disorders. Eur J Neurol. 2010;17:893–902.Google Scholar
  102. 102.
    Mineo TC, Ambrogi V. Outcomes after thymectomy in class I myasthenia gravis. J Thorac Cardiovasc Surg. 2013;145:1319–24.PubMedCrossRefGoogle Scholar
  103. 103.
    Roberts PF, Venuta F, Rendina E, De Giacomo T, Coloni GF, Follette DM, et al. Thymectomy in the treatment of ocular myasthenia gravis. J Thorac Cardiovasc Surg. 2001;122:562–8.PubMedCrossRefGoogle Scholar
  104. 104.
    Gilbert ME, De Sousa EA, Savino PJ. Ocular Myasthenia Gravis treatment: the case against prednisone therapy and thymectomy. Arch Neurol. 2007;64:1790–2.PubMedCrossRefGoogle Scholar
  105. 105.
    Kerty E, Elsais A, Argov Z, Evoli A, Gilhus NE. EFNS/ENS Guidelines for the treatment of ocular myasthenia. Eur J Neurol. 2014;21:687–93.PubMedCrossRefGoogle Scholar
  106. 106.
    Guillermo GR, Téllez-Zenteno JF, Weder-Cisneros N, Mimenza A, Estañol B, Remes-Troche JM, et al. Response of thymectomy: clinical and pathological characteristics among seronegative and seropositive myasthenia gravis patients. Acta Neurol Scand. 2004;109:217–21.PubMedCrossRefGoogle Scholar
  107. 107.
    Yuan HK, Huang BS, Kung SY, Kao KP. The effectiveness of thymectomy on seronegative generalized myasthenia gravis: comparing with seropositive cases. Acta Neurol Scand. 2007;115:181–4.PubMedCrossRefGoogle Scholar
  108. 108.
    Evoli A, Tonali PA, Padua L, Monaco ML, Scuderi F, Batocchi AP, et al. Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis. Brain. 2003;126:2304–11.PubMedCrossRefGoogle Scholar
  109. 109.
    Gilhus NE, Verschuuren JJ. Myasthenia gravis: subgroup classification and therapeutic strategies. Lancet Neurol. 2015;14:1023–36.PubMedCrossRefGoogle Scholar
  110. 110.
    Monden Y, Nakahara K, Kagotani K, Fujii Y, Nanjo S, Masaoka A, et al. Effects of preoperative duration of symptoms on patients with myasthenia gravis. Ann Thorac Surg. 1984;38:287–91.PubMedCrossRefGoogle Scholar
  111. 111.
    Kumar V, Kaminski HJ. Treatment of myasthenia gravis. Curr Neurol Neurosci Rep. 2011;11:89–96.PubMedCrossRefGoogle Scholar
  112. 112.
    Keesey JC. A treatment algorithm for autoimmune myasthenia in adults. Ann NY Acad Sci. 1998;841:753–68.PubMedCrossRefGoogle Scholar
  113. 113.
    Saperstein DS, Barohn RJ. Management of myasthenia gravis. Semin Neurol. 2004;24:41–8.PubMedCrossRefGoogle Scholar
  114. 114.
    Adams C, Theodorescu D, Murphy E, Shandling B. Thymectomy in juvenile myasthenia gravis. J Child Neurol. 1990;5:215–8.PubMedCrossRefGoogle Scholar
  115. 115.
    Andrews PIA. treatment algorithm for autoimmune myasthenia gravis in children. Ann NY Acad Sci. 1998;841:789–802.PubMedCrossRefGoogle Scholar
  116. 116.
    Seybold ME. Thymectomy in childhood myasthenia gravis. Ann NY Acad Sci. 1998;841:731–41.PubMedCrossRefGoogle Scholar
  117. 117.
    Della Marina A, Trippe H, Lutz S, Schara U. Juvenile myasthenia gravis: recommendations for diagnostic approaches and treatment. Neuropediatrics. 2014;45:75–83.PubMedCrossRefGoogle Scholar
  118. 118.
    Rodriguez M, Gomez MR, Howard F, Taylor WF. Myasthenia gravis in children: long-term follow-up. Ann Neurol. 1983;13:504–10.PubMedCrossRefGoogle Scholar
  119. 119.
    Papatestas AE, Genkins G, Kornfeld P, Eisenkraft JB, Fagerstrom RP, Pozner J, et al. Effects of thymectomy in myasthenia gravis. Ann Surg. 1987;206:79–88.PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Shrager JB, Nathan D, Brinster CJ, Yousuf O, Spence A, Chen Z, et al. Outcomes after 151 extended transcervical thymectomies for myasthenia gravis. Ann Thorac Surg. 2006;82:1863–9.PubMedCrossRefGoogle Scholar
  121. 121.
    Ruffini E, Guerrera F, Filosso PL, Bora G, Nex G, Gusmano S, et al. Extended transcervical thymectomy with partial upper sternotomy: results in non-thymomatous patients with myasthenia gravis. Eur J Cardiothorac Surg. 2015;48:448–54.PubMedCrossRefGoogle Scholar
  122. 122.
    Manlulu A, Lee TW, Wan I, Law CY, Chang C, Garzon JC, et al. Video-assisted thoracic surgery thymectomy for nonthymomatous myasthenia gravis. Chest. 2005;128:3454–60.PubMedCrossRefGoogle Scholar
  123. 123.
    Tomulescu V, Sgarbura O, Stanescu C, Valciu C, Campeanu A, Herlea V, et al. Ten-year results of thoracoscopic unilateral extended thymectomy performed in nonthymomatous myasthenia gravis. Ann Surg. 2011;254(5):761.PubMedCrossRefGoogle Scholar
  124. 124.
    Mantegazza R, Baggi F, Bernasconi P, Antozzi C, Confalonieri P, Novellino L, et al. Video-assisted thoracoscopic extended thymectomy and extended transsternal thymectomy (T-3b) in non-thymomatous myasthenia gravis patients: remission after 6 years of follow-up. J Neurol Sci. 2003;212:31–6.PubMedCrossRefGoogle Scholar
  125. 125.
    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;30:525–8.PubMedCrossRefGoogle Scholar
  126. 126.
    Zielinski M, Hauer L, Hauer J, Pankowski J, Nabialek T, Szlubowski A. Comparison of complete remission rates after 5 year follow-up of three different techniques of thymectomy for myasthenia gravis. Eur J Cardiothorac Surg. 2010;37:1137–43.PubMedCrossRefGoogle Scholar
  127. 127.
    Rückert JC, Swierzy M, Ismail M. Comparison of robotic and nonrobotic thoracoscopic thymectomy: a cohort study. J Thorac Cardiovasc Surg. 2011;141:673–7.PubMedCrossRefGoogle Scholar
  128. 128.
    Kirschner PA. Reoperation on the thymus. A critique. Chest Surg Clin N Am. 2001;11:439–45.PubMedGoogle Scholar
  129. 129.
    Pompeo E, Nofroni I, Iavicoli N, Mineo TC. Thoracoscopic completion thymectomy in refractory nonthymomatous myasthenia. Ann Thorac Surg. 2000;70:918–23.PubMedCrossRefGoogle Scholar
  130. 130.
    Ng JK, Ng CS, Underwood MJ, Lau KK. Does repeat thymectomy improve symptoms in patients with refractory myasthenia gravis? Interact Cardiovasc Thorac Surg. 2014;18:376–80.PubMedCrossRefGoogle Scholar
  131. 131.
    Mussi A, Lucchi M, Murri L, Ricciardi R, Luchini L, Angeletti CA. Extended thymectomy in myasthenia gravis: a team-work of neurologist, thoracic surgeon, and anaesthetist may improve the outcome. Eur J Cardiothorac Surg. 2001;19(5):570.PubMedCrossRefGoogle Scholar
  132. 132.
    Houghton A. Variation in outcome of surgical procedures. Br J Surg. 1994;81:653–60.PubMedCrossRefGoogle Scholar
  133. 133.
    Crawford FA, Anderson RP, Clark RE, Grover FL, Kouchoukos NT, Waldhausen JA, et al. Volume requirements for cardiac surgery credentialing: a critical examination. Ann Thorac Surg. 1996;61:12–6.PubMedCrossRefGoogle Scholar
  134. 134.
    Silvestri GA, Handy J, Lackland D, Corley E, Reed CE. Specialists achieve better outcomes than generalists for lung cancer surgery. Chest. 1998;114:675–80.PubMedCrossRefGoogle Scholar
  135. 135.
    Kaminski HJ. Treatment of myasthenia gravis. In: Kaminski HJ, editor. Myasthenia gravis and related disorders. Totowa: Humana Press; 2003. p. 197–221.CrossRefGoogle Scholar
  136. 136.
    Watanabe A, Watanabe T, Obama T, Mawatari T, Ohsawa H, Ichimiya Y, et al. Prognostic factors for myasthenic crisis after transsternal thymectomy in patients with myasthenia gravis. J Thorac Cardiovasc Surg. 2004;127(3):868–76.PubMedCrossRefGoogle Scholar
  137. 137.
    Leventhal SR, Orkin FK, Hirsh RA. Prediction of the need for postoperative mechanical ventilation in myasthenia gravis. Anesthesiology. 1980;53:26–30.PubMedCrossRefGoogle Scholar
  138. 138.
    Krucylak PE, Naunheim KS. Preoperative preparation and anesthetic management of patients with myasthenia gravis. Semin Thorac Cardiovasc Surg. 1999;11:47–53.PubMedCrossRefGoogle Scholar
  139. 139.
    Tripathi M, Kaushik S, Dubey P. The effect of use of pyridostigmine and requirement of vecuronium in patients with myasthenia gravis. J Postgrad Med. 2003;49:311–4.PubMedGoogle Scholar
  140. 140.
    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.PubMedCrossRefGoogle Scholar
  141. 141.
    Jaretzki A III, Phillips L II, Aarli J, Kaminski HJ, Sanders DB. Preoperative preparation of patients with myasthenia gravis for stalls postoperative respiratory complications following thymectomy. Ann Thor Surg. 2003;75:1068–9.CrossRefGoogle Scholar
  142. 142.
    Kadota Y, Horio H, Mori T, Sawabata N, Goto T, Yamashita S, et al. Perioperative management in myasthenia gravis: republication of a systematic review and a proposal by the guideline committee of the Japanese Association for Chest Surgery 2014. Gen Thorac Cardiovasc Surg. 2015;63:201–15.PubMedCrossRefGoogle Scholar
  143. 143.
    Zieliński M, Kuzdzał J, Staniec B, Harazda M, Nabiałek T, Pankowski J, et al. Safety for preoperative use of steroids for transsternal thymectomy in myasthenia gravis. Eur J Cardiothorac Surg. 2004;26:407–11.PubMedCrossRefGoogle Scholar
  144. 144.
    d’Empaire G, Hoaglin DC, Perlo VP, Pontoppidan H. Effect of prethymectomy plasma exchange on postoperative respiratory function in myasthenia gravis. J Thorac Cardiovasc Surg. 1985;89:592–6.PubMedGoogle Scholar
  145. 145.
    Cumming WJK, Hudgson P. The role of plasmapheresis in preparing patients with myasthenia for thymectomy. Muscle Nerve. 1986;9:155–8.CrossRefGoogle Scholar
  146. 146.
    Gotti P, Spinelli A, Marconi G, Duranti R, Gigliotti F, Pizzi A, et al. Comparative effects of plasma exchange and pyridostigmine on expiratory muscle strength and breathing pattern in patients with myasthenia gravis. Thorax. 1995;50:1080–6.CrossRefGoogle Scholar
  147. 147.
    Loach AB, Young AC, Spalding JM, Smith AC. Postoperative management after thymectomy. Br Med J. 1975;1:309–12.PubMedPubMedCentralCrossRefGoogle Scholar
  148. 148.
    Lee HS, Lee HS, Lee HE, Bae MK, Chung KY, Shin HY, et al. Predictive factors for myasthenic crisis after videoscopic thymectomy in patients with myasthenia gravis. Muscle Nerve. 2015;52:216–20.PubMedCrossRefGoogle Scholar
  149. 149.
    Younger DS, Braun NMT, Jaretzki A III, Penn AS, Lovelace AE. Myasthenia gravis: determinants for independent ventilation after transsternal thymectomy. Neurology. 1984;34:336–40.PubMedCrossRefGoogle Scholar
  150. 150.
    Abel M, Eisenkraft JB. Anesthetic implications of myasthenia gravis. Mt Sinai J Med. 2002;69:31–7.PubMedGoogle Scholar
  151. 151.
    Mayer SA. Intensive care of the myasthenic patient. Neurology. 1997;48(Suppl 5):70–81.CrossRefGoogle Scholar
  152. 152.
    Juel VC. Myasthenia gravis: management of myasthenic crisis and perioperative care. Semin Neurol. 2004;24:75–81.PubMedCrossRefGoogle Scholar
  153. 153.
    Wekerle H, Muller-Hermelink HK. The thymus in myasthenia gravis. In: Muller-Hermelink HK, editor. Current topics in pathology. The human thymus. Histophysiology and pathology. New York: Springer; 1986. p. 179–206.Google Scholar
  154. 154.
    Ellis K, Austin JHM, Jaretzki A III. Radiologic detection of thymoma in patients with myasthenia gravis. Am J Radiol. 1988;151:873–81.Google Scholar
  155. 155.
    Falkson CB, Bezjak A, Darling G, Gregg R, Malthaner R, Maziak DE, et al.; Lung Cancer Disease Site Group of Cancer Care Ontario’s Program in Evidence-Based Care. The management of thymoma: a systematic review and practice guideline. J Thorac Oncol. 2009;4:911–9.Google Scholar
  156. 156.
    Shields TW. Thymic tumors. In: Shields TW, LoCicero III J, Reed CE, Feins RH, editors. General thoracic surgery. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2009. p. 2323–62.Google Scholar
  157. 157.
    Miller RG, Rosenberg JA, Gelinas DF, Mitsumoto H, Newman D, Sufit R, et al. Practice parameter: the care of the patient with amyotrophic lateral sclerosis (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology: ALS Practice Parameters Task Force. Neurology. 1999;52:1311–23.PubMedCrossRefGoogle Scholar
  158. 158.
    Kirklin JW, Blackstone EH. Clinical studies with non-randomly assigned treatment. In: Kirklin JW, Barrett-Boyes BG, editors. Cardiac surgery. 2nd ed. New York: Churchill-Livingstone; 1993. p. 269–70.Google Scholar
  159. 159.
    Burns TM, Conaway M, Sanders DB, MG Composite and MG-QOL15 Study Group. The MG composite: a valid and reliable outcome measure for myasthenia gravis. Neurology. 2010;74:1434–40.PubMedPubMedCentralCrossRefGoogle Scholar
  160. 160.
    Keating CP, Kong YX, Tay V, Knight SR, Clarke CP, Wright GM. VATS thymectomy for nonthymomatous myasthenia gravis: standardized outcome assessment using the myasthenia gravis foundation of America clinical classification. Innovations (Phila). 2011;6:104–9.CrossRefGoogle Scholar
  161. 161.
    Liu Z, Yang J, Lin L, Huang J, Jiang G. Unilateral video-assisted thoracoscopic extended thymectomy offers long-term outcomes equivalent to that of the bilateral approach in the treatment of non-thymomatous myasthenia gravis. Interact Cardiovasc Thorac Surg. 2015;21(5):610.PubMedCrossRefGoogle Scholar
  162. 162.
    Prokakis C, Koletsis E, Salakou S, Apostolakis E, Baltayiannis N, Chatzimichalis A, et al. Modified maximal thymectomy for myasthenia gravis: effect of maximal resection on late neurologic outcome and predictors of disease remission. Ann Thorac Surg. 2009;88:1638–45.PubMedCrossRefGoogle Scholar
  163. 163.
    Yoshino I, Hashizume M, Shimada M, Tomikawa M, Tomiyasu M, Suemitsu R, et al. Thoracoscopic thymomectomy with the da Vinci computer-enhanced surgical system. J Thorac Cardiovasc Surg. 2001;122:783–5.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Joshua R. Sonett
    • 1
  • Bianca Bromberger
    • 2
  • Alfred JaretzkiIII
    • 2
  1. 1.Department of Thoracic SurgeryNew York Presbyterian/Columbia University Medical CenterNew YorkUSA
  2. 2.Department of SurgeryNew York Presbyterian Columbia University Medical CenterNew YorkUSA

Personalised recommendations