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Surgical aspects and controversies in the management of medullary thyroid cancer

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Abstract

Medullary thyroid cancer (MTC) accounts for only 4% of thyroid carcinomas but 15% of thyroid cancer deaths. MTC is a tumour of the calcitonin secreting parafollicular C cells in the thyroid which can occur sporadically or be hereditary in multiple endocrine neoplasias type 2 syndromes due to germline RET mutations. Sporadic forms of MTC can also be caused by mutations in the RET protooncogene. MTC commonly presents in a late stage, with 70% of patients presenting with local nodal metastasis. Currently, the only curative treatment for MTC is surgical removal. The aim of this paper is to describe the current guidelines and progressions of the surgical management of MTC and to highlight up-and-coming chemotherapies. A database literature review was completed utilizing PubMed to cumulate the extant literature, screening for most recent guidelines and publications regarding the management of MTC. Current guidelines were described by the American Thyroid Association in 2015. Controversial publications continue to present supporting evidence for varying degrees of thyroidectomy and neck dissections. Recently, researchers have been exploring non-surgical options including external beam radiotherapy and multikinase inhibitors such as vandetanib and cabozantinib for the treatment of MTC. Surgical management of MTC remains controversial and varies significantly dependent on the extent of disease. Chemotherapeutic options have undetermined effects on survival to date.

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References

  1. Sexton PM, Findlay DM, Martin TJ (1999) Calcitonin. Curr Med Chem 6(11):1067–1093

    Article  CAS  PubMed  Google Scholar 

  2. Wells SA Jr, Asa SL, Dralle H et al (2015) Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid 25(6):567–610

    Article  PubMed  PubMed Central  Google Scholar 

  3. Tashjian AH Jr, Melvin EW (1968) Medullary carcinoma of the thyroid gland. Studies of thyrocalcitonin in plasma and tumor extracts. N Engl J Med 279(6):279–83

  4. Kebebew E, Ituarte PH, Siperstein AE et al (2000) Medullary thyroid carcinoma: clinical characteristics, treatment, prognostic factors, and a comparison of staging systems. Cancer 88(5):1139–1148

    Article  CAS  PubMed  Google Scholar 

  5. Lennon P, Deady S, White N et al (2017) Aggressive medullary thyroid cancer, an analysis of the Irish National Cancer Registry. Ir J Med Sci 186(1):89–95

    Article  CAS  PubMed  Google Scholar 

  6. Machens A, Hinze R, Thomusch O, Dralle H (2002) Pattern of nodal metastasis for primary and reoperative thyroid cancer. World J Surg 26(1):22–28

    Article  PubMed  Google Scholar 

  7. Moley JF (2010) Medullary thyroid carcinoma: management of lymph node metastases. J Natl Compr Canc Netw 8(5):549–556

    Article  PubMed  Google Scholar 

  8. Conzo G, Mauriello C, Docimo G et al (2014) Clinicopathological pattern of lymph node recurrence of papillary thyroid cancer. Implications for surgery Int J Surg 12(Suppl 1):S194–S197

    PubMed  Google Scholar 

  9. Takahashi M, Ritz J, Cooper GM (1985) Activation of a novel human transforming gene, ret, by DNA rearrangement. Cell 42(2):581–588

    Article  CAS  PubMed  Google Scholar 

  10. Brandi ML, Gagel RF, Angeli A et al (2001) Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 86(12):5658–5671

    Article  CAS  PubMed  Google Scholar 

  11. Znaczko A, Donnelly DE, Morrison PJ (2014) Epidemiology, clinical features, and genetics of multiple endocrine neoplasia type 2B in a complete population. Oncologist 19(12):1284–1286

    Article  PubMed  PubMed Central  Google Scholar 

  12. Raue F, Frank-Raue K, Grauer A (1994) Multiple endocrine neoplasia type 2. Clinical features and screening. Endocrinol Metab Clin North Am 23(1):137–56

  13. Hazard JB, Hawk WA, Crile G Jr (1959) Medullary (solid) carcinoma of the thyroid; a clinicopathologic entity. J Clin Endocrinol Metab 19(1):152–161

    Article  CAS  PubMed  Google Scholar 

  14. Chen L, Zhao K, Li F, He X (2020) Medullary thyroid carcinoma with elevated serum CEA and Normal serum calcitonin after surgery: A case report and literature review. Front Oncol 10:526716

  15. Gambardella C, Offi C, Patrone R et al (2019) Calcitonin negative medullary thyroid carcinoma: a challenging diagnosis or a medical dilemma? BMC Endocr Disord 19(Suppl 1):45

    Article  PubMed  PubMed Central  Google Scholar 

  16. Johnston PC, Silversides JA, Wallace H et al (2013) Phaeochromocytoma crisis: two cases of undiagnosed phaeochromocytoma presenting after elective nonrelated surgical procedures. Case Rep Anesthesiol 2013:514714

  17. Raue F, Frank-Raue K (2015) Epidemiology and clinical presentation of medullary thyroid carcinoma. Recent Results Cancer Res 204:61–90

    Article  PubMed  Google Scholar 

  18. Elisei R, Cosci B, Romei C et al (2008) Prognostic significance of somatic RET oncogene mutations in sporadic medullary thyroid cancer: a 10-year follow-up study. J Clin Endocrinol Metab 93(3):682–687

    Article  CAS  PubMed  Google Scholar 

  19. Medullary thyroid cancer (2020) In: Association AT, editor. American Thyroid Association

  20. Gremillion G, Fatakia A, Dornelles A, Amedee RG (2012) Intraoperative recurrent laryngeal nerve monitoring in thyroid surgery: is it worth the cost? Ochsner J 12(4):363–366

    PubMed  PubMed Central  Google Scholar 

  21. Viola D, Elisei R (2019) Management of medullary thyroid cancer. Endocrinol Metab Clin North Am 48(1):285–301

    Article  PubMed  Google Scholar 

  22. Essig GF Jr, Porter K, Schneider D et al (2016) Multifocality in sporadic medullary thyroid carcinoma: an international multicenter study. Thyroid 26(11):1563–1572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Miyauchi A, Matsuzuka F, Hirai K et al (2000) Unilateral surgery supported by germline RET oncogene mutation analysis in patients with sporadic medullary thyroid carcinoma. World J Surg 24(11):1367–1372

    Article  CAS  PubMed  Google Scholar 

  24. Miyauchi A, Matsuzuka F, Hirai K et al (2002) Prospective trial of unilateral surgery for nonhereditary medullary thyroid carcinoma in patients without germline RET mutations. World J Surg 26(8):1023–1028

    Article  PubMed  Google Scholar 

  25. Ito Y, Miyauchi A, Yabuta T et al (2009) Alternative surgical strategies and favorable outcomes in patients with medullary thyroid carcinoma in Japan: experience of a single institution. World J Surg 33(1):58–66

    Article  PubMed  Google Scholar 

  26. Machens A, Dralle H (2010) Biomarker-based risk stratification for previously untreated medullary thyroid cancer. J Clin Endocrinol Metab 95(6):2655–2663

    Article  CAS  PubMed  Google Scholar 

  27. Elisei R, Romei C, Renzini G (2012) The timing of total thyroidectomy in RET gene mutation carriers could be personalized and safely planned on the basis of serum calcitonin: 18 years experience at one single center. J Clin Endocrinol Metab 97(2):426–35

  28. Angeletti F, Musholt PB, Musholt TJ (2015) Continuous intraoperative neuromonitoring in thyroid surgery. Surg Technol Int 27:79–85

    PubMed  Google Scholar 

  29. Wojtczak B, Sutkowski K, Kaliszewski K et al (2017) Experience with intraoperative neuromonitoring of the recurrent laryngeal nerve improves surgical skills and outcomes of non-monitored thyroidectomy. Langenbecks Arch Surg 402(4):709–717

    Article  PubMed  Google Scholar 

  30. Pisello F, Geraci G, Lo Nigro C et al (2010) Neck node dissection in thyroid cancer. A review G Chir 31(3):112–118

    CAS  PubMed  Google Scholar 

  31. Cozzaglio L, Coladonato M, Doci R, Gennari L (2006) The lymph node dissection in thyroid carcinoma. Ann Ital Chir 77(3):187–197

    PubMed  Google Scholar 

  32. Machens A, Holzhausen HJ, Dralle H (2004) Skip metastases in thyroid cancer leaping the central lymph node compartment. Arch Surg 139(1):43–45

    Article  PubMed  Google Scholar 

  33. Scollo C, Baudin E, Travagli JP et al (2003) Rationale for central and bilateral lymph node dissection in sporadic and hereditary medullary thyroid cancer. J Clin Endocrinol Metab 88(5):2070–2075

    Article  CAS  PubMed  Google Scholar 

  34. Sobol S, Jensen C, Sawyer W 2nd et al (1985) Objective comparison of physical dysfunction after neck dissection. Am J Surg 150(4):503–509

    Article  CAS  PubMed  Google Scholar 

  35. Roerink SH, Coolen L, Schenning ME et al (2017) High prevalence of self-reported shoulder complaints after thyroid carcinoma surgery. Head Neck 39(2):260–268

    Article  PubMed  Google Scholar 

  36. Roh JL, Kim DH, Park CI (2008) Prospective identification of chyle leakage in patients undergoing lateral neck dissection for metastatic thyroid cancer. Ann Surg Oncol 15(2):424–429

    Article  PubMed  Google Scholar 

  37. Cavallaro G, Iorio O, Centanni M et al (2015) Parathyroid reimplantation in forearm subcutaneous tissue during thyroidectomy: a simple and effective way to avoid hypoparathyroidism. World J Surg 39(8):1936–1942

    Article  PubMed  Google Scholar 

  38. Olson JA Jr., DeBenedetti MK, Baumann DS, Wells SA Jr (1996) Parathyroid autotransplantation during thyroidectomy. Results of long-term follow-up. Ann Surg 223(5):472–8; discussion 8–80.

  39. Martinez SR, Beal SH, Chen A et al (2010) Adjuvant external beam radiation for medullary thyroid carcinoma. J Surg Oncol 102(2):175–178

    Article  PubMed  PubMed Central  Google Scholar 

  40. Schwartz DL, Rana V, Shaw S et al (2008) Postoperative radiotherapy for advanced medullary thyroid cancer–local disease control in the modern era. Head Neck 30(7):883–888

    Article  PubMed  Google Scholar 

  41. Wells SA Jr, Robinson BG, Gagel RF et al (2012) Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol 30(2):134–141

    Article  CAS  PubMed  Google Scholar 

  42. Sherman S, Cohen E (2013) Efficacy of cabozantinib (Cabo) in medullary thyroid cancer (MTC) patients with RAS or RET mutations: results from a phase III study. J Clin Oncol 31

  43. Ceolin L, Duval M, Benini AF et al (2019) Medullary thyroid carcinoma beyond surgery: advances, challenges, and perspectives. Endocr Relat Cancer 26(9):R499–R518

    Article  CAS  PubMed  Google Scholar 

  44. Elisei R, Schlumberger MJ, Muller SP et al (2013) Cabozantinib in progressive medullary thyroid cancer. J Clin Oncol 31(29):3639–3646

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Wedge SR, Ogilvie DJ, Dukes M et al (2002) ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res 62(16):4645–4655

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Royal College of Surgeons in Ireland, Dublin, Ireland

    Katerina Green

  2. Department of Otolaryngology, Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin, Ireland

    Justin Hintze & James Paul O’Neill

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  1. Katerina Green
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  2. Justin Hintze
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  3. James Paul O’Neill
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Correspondence to Katerina Green.

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Green, K., Hintze, J. & O’Neill, J.P. Surgical aspects and controversies in the management of medullary thyroid cancer. Ir J Med Sci 191, 2461–2466 (2022). https://doi.org/10.1007/s11845-021-02886-8

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  • DOI: https://doi.org/10.1007/s11845-021-02886-8

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