Advertisement

Thymic Pathology and Myasthenia Gravis

  • Calvin S. H. Ng
  • Anthony P. C. Yim
Chapter

Abstract

From a historical perspective, myasthenia gravis (MG) was first described in 1672 by an Oxford clinician, Sir Thomas Willis, who noted a patient with temporary loss of speech [1]. It wasn’t until two and a half centuries later in 1911 that the first thymectomy was performed by Ferdinard Sauerbruch in Zurich on a 21-year-old woman with hyperthyroidism and MG. Thymectomy was performed in an attempt to treat her hyperthyroidism, and following surgery both conditions showed improvement temporarily. In 1934, Mary Walker recognized clinical similarities between MG and curaré poisoning and hence introduced the anticholinesterase treatment, physostigmine, producing significant improvement in muscle strength for a MG patient. This was an important discovery implicating the pathogenesis of MG at the neuromuscular junction. Later in 1944, Alfred Blalock at Johns Hopkins reported improvement in MG patients following resection of normal thymus and also introduced this as a surgical therapy for this condition. Clinical use of edrophonium was introduced around 1950 and later taken over by the more popular pyridostigmine. John Simpson first proposed in 1960 that MG might be an autoimmune disease, which was later confirmed in 1973 by Patrick and Lindstrom through animal studies by immunizing rabbits with purified acetylcholine receptors. It is now common knowledge that MG is an autoimmune disorder of the postsynaptic nicotinic acetylcholine receptor, characterized by weakness and fatiguability of voluntary muscles. The ocular muscles are frequently involved, rendering ptosis and diplopia the most common modes of presentation. Despite the discovery of the condition centuries ago, considerable controversies still remain over its diagnosis, natural history, and therapy both medical and surgical. Nevertheless, thymectomy is now an established therapy in the management of generalized MG in conjunction with medical treatment. A meta-analysis of 28 controlled studies has previously shown that MG patients undergoing thymectomy were twice as likely to attain medication-free remission, 1.6 times as likely to become asymptomatic, and 1.7 times as likely to improve. Different demographics and baseline characteristics however existed between groups [2]. A recent randomized prospective trial investigating the role of thymectomy for myasthenia gravis has shown improved clinical outcomes over a 3-year period in patients with nonthymomatous myasthenia gravis [3]. Uncertainties remain over the role of thymectomy for patients with purely ocular symptom and those with late onset of disease.

Keywords

Myasthenia gravis Single Port Thymectomy Thymoma Uniportal Video-assisted thoracic Surgery (VATS) 

References

  1. 1.
    Pascuzzi R. The history of myasthenia gravis. Neurol Clin. 1994;12:231–42.CrossRefPubMedGoogle Scholar
  2. 2.
    Gronseth GS, Barohn RJ. Practice parameter: thymectomy for autoimmune myasthenia gravis (an evidence-base review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2000;55:7–15.CrossRefPubMedGoogle Scholar
  3. 3.
    Wolfe GI, Kaminski HJ, Aban IB, Minisman G, Kuo HC, Marx A, et al. MGTX study group. Randomized trial of thymectomy in myasthenia gravis. N Engl J Med. 2016;375(6):511–22.Google Scholar
  4. 4.
    Calhoun RF, Ritter JH, Guthrie TJ, Pestronk A, Meyers BF, Patterson GA, Pohl MS, Cooper JD. Results of transcervical thymectomy for myasthenia gravis in 100 consecutive patients. Ann Surg. 1999;230:555–9.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Milanez de Campos JR, Filomeno LTB, Marchiori PE, Jatene FB. Parital sternotomy approach to the thymus. In: APC Y, Hazelrigg SR, Izzat MB, et al., editors. Minimal access cardiothoracic surgery. Philadelphia: WB Saunders; 2000. p. 205–8.Google Scholar
  6. 6.
    Granone P, Margaritora S, Cesario A, Galetta D. Thymectomy in myasthenia gravis via video assisted infra-mammary cosmetic incision. Eur J Cardiothorac Surg. 1999;15:861–3.CrossRefPubMedGoogle Scholar
  7. 7.
    Sugarbaker DJ. Thoracoscopy in the management of anterior mediastinal masses. Ann Thorac Surg. 1993;56:653–6.CrossRefPubMedGoogle Scholar
  8. 8.
    Coosemans W, Lerut TE, Van Raemdonck DE. Thoracoscopic surgery: the Belgian experience. Ann Thorac Surg. 1993;56:721–30.CrossRefPubMedGoogle Scholar
  9. 9.
    Yim APC. Paradigm shift in surgical approaches to thymectomy. ANZ J Surg. 2002;72:40–5.CrossRefPubMedGoogle Scholar
  10. 10.
    Yim APC, Low JM, Ng SK, Ho JK, Liu KK. Video-assisted thoracoscopic surgery in the paediatric population. J Paediatr Child Health. 1995;31:192–6.CrossRefPubMedGoogle Scholar
  11. 11.
    Novellino L, Longoni M, Spinelli L, Andretta M, Cozzi M, Faillace G, Vitellaro M, De Benedetti D, Pezzuoli G. “Extended” thymectomy without sternotomy, performed by cervicotomy and thoracoscopic techniques in the treatment of myasthenia gravis. Int Surg. 1994;79:378–81.PubMedGoogle Scholar
  12. 12.
    Shiono H, Kadota Y, Hayashi A, Okumura M. Comparison of outcomes after extended thymectomy for myasthenia gravis: bilateral thoracoscopic approach versus sternotomy. Surg Laparosc Endosc Percutan Tech. 2009;19:424–7.CrossRefPubMedGoogle Scholar
  13. 13.
    Bodner J, Wykypiel H, Greiner A, Kirchmayr W, Freund MC, Margreiter R, Schmid T. Early experience with robot-assisted surgery for mediastinal masses. Ann Thorac Surg. 2004;78:259–65.CrossRefPubMedGoogle Scholar
  14. 14.
    Ng CSH, Lau KKW, Gonzalez-Rivas D, Rocco G. Evolution in surgical approach and techniques for lung cancer. Thorax. 2013;68:681.CrossRefPubMedGoogle Scholar
  15. 15.
    Suda T, Sugimura H, Tochii D, Kihara M, Hattori Y. Single-port thymectomy through an infrasternal approach. Ann Thorac Surg. 2012;93:334–6.CrossRefPubMedGoogle Scholar
  16. 16.
    Yim APC, Kay RLC, Izzat MB, Ng SK. Video-assisted thoracoscopic thymectomy for myasthenia gravis. Semin Thorac Cardiovasc Surg. 1999;11:65–73.CrossRefPubMedGoogle Scholar
  17. 17.
    El-Dawlatly AA, Ashour MH. Anesthesia for thymectomy in myasthenia gravis: a non-muscle-relaxant technique. Anaesth Intensive Care. 1994;22:458–60.PubMedGoogle Scholar
  18. 18.
    Yim AP. Minimizing chest wall trauma in video assisted thoracic surgery. J Thorac Cardiovasc Surg. 1995;109:1255–6.CrossRefPubMedGoogle Scholar
  19. 19.
    Yim APC, Kay RLC, Ho JKS. Video-assisted thoracoscopic thymectomy for myasthenia gravis. Chest. 1995;108:1440–3.CrossRefPubMedGoogle Scholar
  20. 20.
    Ng CS, Wong RH, Lau RW, Yim AP. Minimizing chest wall trauma in single-port video-assisted thoracic surgery. J Thorac Cardiovasc Surg. 2014;147:1095–6.CrossRefPubMedGoogle Scholar
  21. 21.
    Ng CSH, Wong RHL, Lau RWH, Yim APC. Single port video-assisted thoracic surgery: advancing scope technology. Eur J Cardiothorac Surg. 2014. pii: ezu236. [Epub ahead of print].  https://doi.org/10.1093/ejcts/ezu236.
  22. 22.
    Ng CSH, Rocco G, Wong RHL, Lau RWH, Yu SCH, Yim APC. Uniportal and single incision video assisted thoracic surgery- the state of the art. Interact Cardiovasc Thorac Surg. 2014. pii: ivu200. [Epub ahead of print].  https://doi.org/10.1093/icvts/ivu200.
  23. 23.
    Ohta M, Hirabayasi H, Okumura M, Minami M, Matsuda H. Thoracoscopic thymectomy using anterior chest wall lifting method. Ann Thorac Surg. 2003;76:1310–1.CrossRefPubMedGoogle Scholar
  24. 24.
    Manlulu A, Lee TW, Wan I, Law CY, Chang C, Garzon JC, Yim A. VATS thymectomy for nonthymomatous myasthenia gravis. Chest. 2005;128:3454–60.CrossRefPubMedGoogle Scholar
  25. 25.
    Jaretzki A III, Penn AS, Younger DS, Wolff M, Olarte MR, Lovelace RE, Rowland LP. “Maximal” thymectomy for myasthenia gravis. Results. J Thorac Cardiovasc Surg. 1988;95:747–57.PubMedGoogle Scholar
  26. 26.
    Olanow CW, Wechsler AS, Sirontkin-Roses M, Stajich J, Roses AD. Thymectomy as primary therapy in myasthenia gravis. Ann N Y Acad Sci. 1987;505:595–606.CrossRefPubMedGoogle Scholar
  27. 27.
    Cooper JD, Al-Jilaihawa AN, Pearson FG, Humphrey JG, Humphrey HE. An improved technique to facilitate transcervical thymectomy for myasthenia gravis. Ann Thorac Surg. 1988;45:242–7.CrossRefPubMedGoogle Scholar
  28. 28.
    Shrager JB, Deeb ME, Mick R, Brinster CJ, Childers HE, Marshall MB, Kucharczuk JC, Galetta SL, Bird SJ, Kaiser LR. Transcervical thymectomy for myasthenia gravis achieves results comparable to thymectomy by sternotomy. Ann Thorac Surg. 2002;74:320–6.CrossRefPubMedGoogle Scholar
  29. 29.
    Fukai I, Funato Y, Mizuno T, Hashimoto T, Masaoka A. Distribution of thymic tissue in the mediastinal adipose tissue. J Thorac Cardiovasc Surg. 1991;101:1099–102.PubMedGoogle Scholar
  30. 30.
    Pompeo E, Nofroni I, Iavicoli N, Mineo TC. Thoracoscopic completion thymectomy in refractory nonthymomatous myasthenia. Ann Thorac Surg. 2000;70:918–23.CrossRefPubMedGoogle Scholar
  31. 31.
    Meyer DM, Herbert MA, Sobhani NC, et al. Comparative clinical outcomes of thymectomy for myasthenia gravis performed by extended transsternal and minimal invasive approaches. Ann Thorac Surg. 2009;87:385–91.CrossRefPubMedGoogle Scholar
  32. 32.
    Shrager JB, Nathan D, Brinster CJ, et al. Outcomes after 151 extended transcervical thymectomies for myasthenia gravis. Ann Thorac Surg. 2006;82:1863–9.CrossRefPubMedGoogle Scholar
  33. 33.
    Ng J, Ng CSH, Underwood MJ, Lau KKW. Does repeat thymectomy improve symptoms in patients with refractory myasthenia gravis? Interact Cardiovasc Thorac Surg. 2014;18:376–80.CrossRefPubMedGoogle Scholar
  34. 34.
    Rückert JC, Wlater M, Müller JM. Pulmonary function after thoracoscopic thymectomy versus median sternotomy for myasthenia gravis. Ann Thorac Surg. 2000;70:1656–61.CrossRefPubMedGoogle Scholar
  35. 35.
    Mineo TC, Pompeo E, Lerut TE, Bernardi G, Coosemans W, Nofroni I. Thoracscopic thymectomy in autoimmune myasthenia gravis: results of left sided approach. Ann Thorac Surg. 2000;69:1537–41.CrossRefPubMedGoogle Scholar
  36. 36.
    Yim APC. Thoracoscopic thymectomy: which side to approach? Ann Thorac Surg. 1997;64:584 [Letter].Google Scholar
  37. 37.
    Mack MJ, Landreneau RJ, Yim AP, Hazelrigg SR, Scruggs GR. Results of video-assisted thymectomy in patients with myasthenia gravis. J Thorac Cardiovasc Surg. 1996;112:1352–60.CrossRefPubMedGoogle Scholar
  38. 38.
    DeFilippi VJ, Richman DP, Ferguson MK. Transcervical thymectomy for myasthenia gravis. Ann Thorac Surg. 1994;57:194–7.CrossRefPubMedGoogle Scholar
  39. 39.
    Mulder DG, Graves M, Hermann C. Thymectomy for myasthenia gravis: recent observations and comparisons with past experience. Ann Thorac Surg. 1989;48:551–5.CrossRefPubMedGoogle Scholar
  40. 40.
    Nussbaum MS, Rosenthal GJ, Samaha FJ, Grinvalsky HT, Quinlan JG, Schmerler M, Fischer JE. Management of myasthenia gravis by extended thymectomy with anterior mediastinal tumor. Surgery. 1992;112:681–8.PubMedGoogle Scholar
  41. 41.
    Savcenko M, Wendt GK, Prince SL, Mack MJ. Video-assisted thymectomy for myasthenia gravis: an update of a single institution experience. Eur J Cardiothorac Surg. 2002;22:978–83.CrossRefPubMedGoogle Scholar
  42. 42.
    Mantegazza R, Baggi F, Bernasconi P, Antozzi C, Confalonieri P, Novellino L, Spinelli L, Ferro MT, Beghi E, Cornelio F. 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;212:31–6.CrossRefPubMedGoogle Scholar
  43. 43.
    Tomulescu V, Ion V, Kosa A, Sgarbura O, Popescu I. Thoracoscopic thymectomy mid-term results. Ann Thorac Surg. 2006;82:1003–8.CrossRefPubMedGoogle Scholar
  44. 44.
    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;24:677–83.CrossRefPubMedGoogle Scholar
  45. 45.
    Wright GM, Barnett S, Clarke CP. Video-assisted thoracoscopic thymectomy for myasthenia gravis. Intern Med J. 2002;32:367–71.CrossRefPubMedGoogle Scholar
  46. 46.
    Masaoka A, Monden Y, Nakahara K, Tanioka T. Follow up study of thymoma with references to their clinical stages. Cancer. 1981;48:2485–92.CrossRefPubMedGoogle Scholar
  47. 47.
    Ye B, Tantai JC, Ge XX, Li W, Feng J, Cheng M, Shi JX, Zhao H. Surgical techniques for early-stage thymoma: video-assisted thoracoscopic thymectomy versus transsternal thymectomy. J Thorac Cardiovasc Surg. 2014;147:1599–603.CrossRefPubMedGoogle Scholar
  48. 48.
    Yu L, Zhang XJ, Ma S, Li F, Zhang YF. Thoracoscopic thymectomy for myasthenia gravis with and without thymoma: a single-center experience. Ann Thorac Surg. 2012;93:240–4.CrossRefPubMedGoogle Scholar
  49. 49.
    Zielinski M, Kuzdzal J, Szlubowski A, Soja J. Transcervial-subxiphoid-videothoracoscopic ‘maximal’ thymectomy-operative technique and early results. Ann Thorac Surg. 2004;78:404–10.CrossRefPubMedGoogle Scholar
  50. 50.
    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.CrossRefPubMedGoogle Scholar
  51. 51.
    Uchiyama A, Shimizu S, Murai H, Kuroki S, Okido M, Tanaka M. Infrasternal mediastinoscopic thymectomy in myasthenia gravis: surgical results in 23 patients. Ann Thorac Surg. 2001;72:1902–5.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag London Ltd., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Cardiothoracic Surgery, Department of SurgeryThe Chinese University of Hong KongShatinHong Kong

Personalised recommendations