The surgical treatment of medullary thyroid carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

SU Zhe ,  HU Ya

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, P. R. China;

Corresponding author：

HU Ya, Email: huyafrank@sohu.com

Keywords：

medullary thyroid carcinoma; surgery; lymph node dissection; review

DOI：

10.7507/1007-9424.201804026

Video：

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Objective To summarize the clinical and research status in the surgical management of medullary thyroid carcinoma. Methods The related literatures on treatment of medullary thyroid carcinoma were collected and reviewed. Results A total thyroidectomy and dissection of the lymph nodes in the central compartment were effective treatments for patients with medullary thyroid carcinoma. The extent of lateral compartment lymph-node dissection did not reach an agreement. Prophylactic thyroidectomy was suggested for patients with a RET (rearranged during transfection) germline mutation. Palliative therapy was the main treatment of metastatic medullary thyroid carcinoma. Conclusions Surgery is the mainstay of treatment for medullary thyroid carcinoma. The combination of preoperative assessment, genetic testing, and appropriate surgical strategy may improve the prognosis of patients with medullary thyroid carcinoma.

Citation： SU Zhe, HU Ya. The surgical treatment of medullary thyroid carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2018, 25(10): 1276-1280. doi: 10.7507/1007-9424.201804026 Copy

1.	Hundahl SA, Fleming ID, Fremgen AM, et al. A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985-1995[see commetns]. Cancer, 1998, 83(12): 2638-2648.
2.	Konstantinidis A, Stang M, Roman SA, et al. Surgical management of medullary thyroid carcinoma. Updates Surg, 2017, 69(2): 151-160.
3.	Wells SA Jr, Asa SL, Dralle H, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid, 2015, 25(6): 567-610.
4.	Qu N, Shi RL, Lu ZW, et al. Metastatic lymph node ratio can further stratify risk for mortality in medullary thyroid cancer patients: a population-based analysis. Oncotarget, 2016, 7(40): 65937-65945.
5.	Jin LX, Moley JF. Surgery for lymph node metastases of medullary thyroid carcinoma: a review. Cancer, 2016, 122(3): 358-366.
6.	Greenblatt DY, Elson D, Mack E, et al. Initial lymph node dissection increases cure rates in patients with medullary thyroid cancer. Asian J Surg, 2007, 30(2): 108-112.
7.	Modigliani E, Cohen R, Campos JM, et al. Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. The GETC Study Group. Groupe d'étude des tumeurs à calcitonine. Clin Endocrinol (Oxf), 1998, 48(3): 265-273.
8.	Kim C, Baek JH, Ha E, et al. Ultrasonography features of medullary thyroid cancer as predictors of its biological behavior. Acta Radiol, 2017, 58(4): 414-422.
9.	Oh HS, Kwon H, Song E, et al. Preoperative clinical and sonographic predictors for lateral cervical lymph node metastases in sporadic medullary thyroid carcinoma. Thyroid, 2018, 28(3): 362-368.
10.	Moley JF. Medullary thyroid carcinoma: management of lymph node metastases. J Natl Compr Canc Netw, 2010, 8(5): 549-556.
11.	NCCN. Evidence-Based Cancer Guidelines, Oncology Drug Compendium, Oncology Continuing Medical Education. 2018-06-30. https://www.nccn.org/.
12.	Brauckhoff M, Machens A, Lorenz K, et al. Surgical curability of medullary thyroid cancer in multiple endocrine neoplasia 2B: a changing perspective. Ann Surg, 2014, 259(4): 800-806.
13.	Sosa JA, Tuggle CT, Wang TS, et al. Clinical and economic outcomes of thyroid and parathyroid surgery in children. J Clin Endocrinol Metab, 2008, 93(8): 3058-3065.
14.	Tuggle CT, Roman SA, Wang TS, et al. Pediatric endocrine surgery: who is operating on our children? Surgery, 2008, 144(6): 869-877.
15.	Rusinek D, Chmielik E, Krajewska J, et al. Current advances in thyroid cancer management. are we ready for the epidemic rise of diagnoses? Int J Mol Sci, 2017, 18(8): E1817.
16.	Shepet K, Alhefdhi A, Lai N, et al. Hereditary medullary thyroid cancer: age-appropriate thyroidectomy improves disease-free survival. Ann Surg Oncol, 2013, 20(5): 1451-1455.
17.	Machens A, Dralle H. Biomarker-based risk stratification for previously untreated medullary thyroid cancer. J Clin Endocrinol Metab, 2010, 95(6): 2655-2663.
18.	Machens A, Hauptmann S, Dralle H. Prediction of lateral lymph node metastases in medullary thyroid cancer. Br J Surg, 2008, 95(5): 586-591.
19.	Puccini M, Manca G, Ugolini C, et al. Interest of sentinel node biopsy in apparently intrathyroidal medullary thyroid cancer: a pilot study. J Endocrinol Invest, 2014, 37(9): 829-834.
20.	Jiang K, Lei J, Chen W, et al. Association of the preoperative neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios with lymph node metastasis and recurrence in patients with medullary thyroid carcinoma. Medicine (Baltimore), 2016, 95(40): e5079.
21.	Jiang K, Lei J, Li C, et al. Comparison of the prognostic values of selected inflammation based scores in patients with medullary thyroid carcinoma: a pilot study. J Surg Oncol, 2017, 116(3): 281-287.
22.	De Crea C, Raffaelli M, Milano V, et al. Intraoperative high-dose calcium stimulation test in patients with sporadic medullary thyroid carcinoma is highly accurate in predicting lateral neck metastases. Surgery, 2016, 159(1): 70-76.
23.	Aubert S, Berdelou A, Gnemmi V, et al. Large sporadic thyroid medullary carcinomas: predictive factors for lymph node involvement. Virchows Arch, 2018, 472(3): 461-468.
24.	Skinner MA, Moley JA, Dilley WG, et al. Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A. N Engl J Med, 2005, 353(11): 1105-1113.
25.	Gosnell JE, Duh QY. Medullary thyroid carcinoma-we should do better. JAMA Surg, 2018, 153(1): 59.
26.	Randle RW, Balentine CJ, Leverson GE, et al. Trends in the presentation, treatment, and survival of patients with medullary thyroid cancer over the past 30 years. Surgery, 2017, 161(1): 137-146.
27.	Essig GF Jr, Porter K, Schneider D, et al. Fine needle aspiration and medullary thyroid carcinoma: the risk of inadequate preoperative evaluation and initial surgery when relying upon FNAB cytology alone. Endocr Pract, 2013, 19(6): 920-927.
28.	Simões-Pereira J, Bugalho MJ, Limbert E, et al. Retrospective analysis of 140 cases of medullary thyroid carcinoma followed-up in a single institution. Oncol Lett, 2016, 11(6): 3870-3874.
29.	Kuo EJ, Sho S, Li N, et al. Risk ractors associated with reoperation and disease-specific mortality in patients with medullary thyroid carcinoma. JAMA Surg, 2018, 153(1): 52-59.
30.	Randle RW, Bates MF, Schneider DF, et al. Survival in patients with medullary thyroid cancer after less than the recommended initial operation. J Surg Oncol, 2018, 117(6): 1211-1216.
31.	Esfandiari NH, Hughes DT, Yin H, et al. The effect of extent of surgery and number of lymph node metastases on overall survival in patients with medullary thyroid cancer. J Clin Endocrinol Metab, 2014, 99(2): 448-454.
32.	Kandil E, Gilson MM, Alabbas HH, et al. Survival implications of cervical lymphadenectomy in patients with medullary thyroid cancer. Ann Surg Oncol, 2011, 18(4): 1028-1034.
33.	Rendl G, Manzl M, Hitzl W, et al. Long-term prognosis of medullary thyroid carcinoma. Clin Endocrinol (Oxf), 2008, 69(3): 497-505.
34.	Siironen P, Hagström J, Mäenpää HO, et al. Lymph node metastases and elevated postoperative calcitonin: predictors of poor survival in medullary thyroid carcinoma. Acta Oncol, 2016, 55(3): 357-364.
35.	Geller G, Laskin J, Cheung WY, et al. A retrospective review of the multidisciplinary management of medullary thyroid cancer: eligibility for systemic therapy. Thyroid Res, 2017, 10: 6.
36.	Fialkowski E, DeBenedetti M, Moley J. Long-term outcome of reoperations for medullary thyroid carcinoma. World J Surg, 2008, 32(5): 754-765.
37.	Machens A, Dralle H. Benefit-risk balance of reoperation for persistent medullary thyroid cancer. Ann Surg, 2013, 257(4): 751-757.
38.	Tufano RP, Bishop J, Wu G. Reoperative central compartment dissection for patients with recurrent/persistent papillary thyroid cancer: efficacy, safety, and the association of the BRAF mutation. Laryngoscope, 2012, 122(7): 1634-1640.
39.	Schneider R, Randolph GW, Sekulla C, et al. Continuous intraoperative vagus nerve stimulation for identification of imminent recurrent laryngeal nerve injury. Head Neck, 2013, 35(11): 1591-1598.
40.	Schmid KW. Lymph node and distant metastases of thyroid gland cancer. Metastases in the thyroid glands. Pathologe, 2015, 36 Suppl 2: 171-175.
41.	Fromigué J, De Baere T, Baudin E, et al. Chemoembolization for liver metastases from medullary thyroid carcinoma. J Clin Endocrinol Metab, 2006, 91(7): 2496-2499.
42.	Wertenbroek MW, Links TP, Prins TR, et al. Radiofrequency ablation of hepatic metastases from thyroid carcinoma. Thyroid, 2008, 18(10): 1105-1110.
43.	French JD, Bible K, Spitzweg C, et al. Leveraging the immune system to treat advanced thyroid cancers. Lancet Diabetes Endocrinol, 2017, 5(6): 469-481.
44.	Nelkin B. Recent advances in the biology and therapy of medullary thyroid carcinoma. F1000Res, 2017, 6: 2184.
45.	Wells SA Jr, Robinson BG, Gagel RF, et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase Ⅲ trial. J Clin Oncol, 2012, 30(2): 134-141.
46.	Elisei R, Schlumberger MJ, Müller SP, et al. Cabozantinib in progressive medullary thyroid cancer. J Clin Oncol, 2013, 31(29): 3639-3646.
47.	Pappa T, Alevizaki M. Management of hereditary medullary thyroid carcinoma. Endocrine, 2016, 53(1): 7-17.

1. Hundahl SA, Fleming ID, Fremgen AM, et al. A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985-1995[see commetns]. Cancer, 1998, 83(12): 2638-2648.
2. Konstantinidis A, Stang M, Roman SA, et al. Surgical management of medullary thyroid carcinoma. Updates Surg, 2017, 69(2): 151-160.
3. Wells SA Jr, Asa SL, Dralle H, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid, 2015, 25(6): 567-610.
4. Qu N, Shi RL, Lu ZW, et al. Metastatic lymph node ratio can further stratify risk for mortality in medullary thyroid cancer patients: a population-based analysis. Oncotarget, 2016, 7(40): 65937-65945.
5. Jin LX, Moley JF. Surgery for lymph node metastases of medullary thyroid carcinoma: a review. Cancer, 2016, 122(3): 358-366.
6. Greenblatt DY, Elson D, Mack E, et al. Initial lymph node dissection increases cure rates in patients with medullary thyroid cancer. Asian J Surg, 2007, 30(2): 108-112.
7. Modigliani E, Cohen R, Campos JM, et al. Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. The GETC Study Group. Groupe d'étude des tumeurs à calcitonine. Clin Endocrinol (Oxf), 1998, 48(3): 265-273.
8. Kim C, Baek JH, Ha E, et al. Ultrasonography features of medullary thyroid cancer as predictors of its biological behavior. Acta Radiol, 2017, 58(4): 414-422.
9. Oh HS, Kwon H, Song E, et al. Preoperative clinical and sonographic predictors for lateral cervical lymph node metastases in sporadic medullary thyroid carcinoma. Thyroid, 2018, 28(3): 362-368.
10. Moley JF. Medullary thyroid carcinoma: management of lymph node metastases. J Natl Compr Canc Netw, 2010, 8(5): 549-556.
11. NCCN. Evidence-Based Cancer Guidelines, Oncology Drug Compendium, Oncology Continuing Medical Education. 2018-06-30. https://www.nccn.org/.
12. Brauckhoff M, Machens A, Lorenz K, et al. Surgical curability of medullary thyroid cancer in multiple endocrine neoplasia 2B: a changing perspective. Ann Surg, 2014, 259(4): 800-806.
13. Sosa JA, Tuggle CT, Wang TS, et al. Clinical and economic outcomes of thyroid and parathyroid surgery in children. J Clin Endocrinol Metab, 2008, 93(8): 3058-3065.
14. Tuggle CT, Roman SA, Wang TS, et al. Pediatric endocrine surgery: who is operating on our children? Surgery, 2008, 144(6): 869-877.
15. Rusinek D, Chmielik E, Krajewska J, et al. Current advances in thyroid cancer management. are we ready for the epidemic rise of diagnoses? Int J Mol Sci, 2017, 18(8): E1817.
16. Shepet K, Alhefdhi A, Lai N, et al. Hereditary medullary thyroid cancer: age-appropriate thyroidectomy improves disease-free survival. Ann Surg Oncol, 2013, 20(5): 1451-1455.
17. Machens A, Dralle H. Biomarker-based risk stratification for previously untreated medullary thyroid cancer. J Clin Endocrinol Metab, 2010, 95(6): 2655-2663.
18. Machens A, Hauptmann S, Dralle H. Prediction of lateral lymph node metastases in medullary thyroid cancer. Br J Surg, 2008, 95(5): 586-591.
19. Puccini M, Manca G, Ugolini C, et al. Interest of sentinel node biopsy in apparently intrathyroidal medullary thyroid cancer: a pilot study. J Endocrinol Invest, 2014, 37(9): 829-834.
20. Jiang K, Lei J, Chen W, et al. Association of the preoperative neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios with lymph node metastasis and recurrence in patients with medullary thyroid carcinoma. Medicine (Baltimore), 2016, 95(40): e5079.
21. Jiang K, Lei J, Li C, et al. Comparison of the prognostic values of selected inflammation based scores in patients with medullary thyroid carcinoma: a pilot study. J Surg Oncol, 2017, 116(3): 281-287.
22. De Crea C, Raffaelli M, Milano V, et al. Intraoperative high-dose calcium stimulation test in patients with sporadic medullary thyroid carcinoma is highly accurate in predicting lateral neck metastases. Surgery, 2016, 159(1): 70-76.
23. Aubert S, Berdelou A, Gnemmi V, et al. Large sporadic thyroid medullary carcinomas: predictive factors for lymph node involvement. Virchows Arch, 2018, 472(3): 461-468.
24. Skinner MA, Moley JA, Dilley WG, et al. Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A. N Engl J Med, 2005, 353(11): 1105-1113.
25. Gosnell JE, Duh QY. Medullary thyroid carcinoma-we should do better. JAMA Surg, 2018, 153(1): 59.
26. Randle RW, Balentine CJ, Leverson GE, et al. Trends in the presentation, treatment, and survival of patients with medullary thyroid cancer over the past 30 years. Surgery, 2017, 161(1): 137-146.
27. Essig GF Jr, Porter K, Schneider D, et al. Fine needle aspiration and medullary thyroid carcinoma: the risk of inadequate preoperative evaluation and initial surgery when relying upon FNAB cytology alone. Endocr Pract, 2013, 19(6): 920-927.
28. Simões-Pereira J, Bugalho MJ, Limbert E, et al. Retrospective analysis of 140 cases of medullary thyroid carcinoma followed-up in a single institution. Oncol Lett, 2016, 11(6): 3870-3874.
29. Kuo EJ, Sho S, Li N, et al. Risk ractors associated with reoperation and disease-specific mortality in patients with medullary thyroid carcinoma. JAMA Surg, 2018, 153(1): 52-59.
30. Randle RW, Bates MF, Schneider DF, et al. Survival in patients with medullary thyroid cancer after less than the recommended initial operation. J Surg Oncol, 2018, 117(6): 1211-1216.
31. Esfandiari NH, Hughes DT, Yin H, et al. The effect of extent of surgery and number of lymph node metastases on overall survival in patients with medullary thyroid cancer. J Clin Endocrinol Metab, 2014, 99(2): 448-454.
32. Kandil E, Gilson MM, Alabbas HH, et al. Survival implications of cervical lymphadenectomy in patients with medullary thyroid cancer. Ann Surg Oncol, 2011, 18(4): 1028-1034.
33. Rendl G, Manzl M, Hitzl W, et al. Long-term prognosis of medullary thyroid carcinoma. Clin Endocrinol (Oxf), 2008, 69(3): 497-505.
34. Siironen P, Hagström J, Mäenpää HO, et al. Lymph node metastases and elevated postoperative calcitonin: predictors of poor survival in medullary thyroid carcinoma. Acta Oncol, 2016, 55(3): 357-364.
35. Geller G, Laskin J, Cheung WY, et al. A retrospective review of the multidisciplinary management of medullary thyroid cancer: eligibility for systemic therapy. Thyroid Res, 2017, 10: 6.
36. Fialkowski E, DeBenedetti M, Moley J. Long-term outcome of reoperations for medullary thyroid carcinoma. World J Surg, 2008, 32(5): 754-765.
37. Machens A, Dralle H. Benefit-risk balance of reoperation for persistent medullary thyroid cancer. Ann Surg, 2013, 257(4): 751-757.
38. Tufano RP, Bishop J, Wu G. Reoperative central compartment dissection for patients with recurrent/persistent papillary thyroid cancer: efficacy, safety, and the association of the BRAF mutation. Laryngoscope, 2012, 122(7): 1634-1640.
39. Schneider R, Randolph GW, Sekulla C, et al. Continuous intraoperative vagus nerve stimulation for identification of imminent recurrent laryngeal nerve injury. Head Neck, 2013, 35(11): 1591-1598.
40. Schmid KW. Lymph node and distant metastases of thyroid gland cancer. Metastases in the thyroid glands. Pathologe, 2015, 36 Suppl 2: 171-175.
41. Fromigué J, De Baere T, Baudin E, et al. Chemoembolization for liver metastases from medullary thyroid carcinoma. J Clin Endocrinol Metab, 2006, 91(7): 2496-2499.
42. Wertenbroek MW, Links TP, Prins TR, et al. Radiofrequency ablation of hepatic metastases from thyroid carcinoma. Thyroid, 2008, 18(10): 1105-1110.
43. French JD, Bible K, Spitzweg C, et al. Leveraging the immune system to treat advanced thyroid cancers. Lancet Diabetes Endocrinol, 2017, 5(6): 469-481.
44. Nelkin B. Recent advances in the biology and therapy of medullary thyroid carcinoma. F1000Res, 2017, 6: 2184.
45. Wells SA Jr, Robinson BG, Gagel RF, et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase Ⅲ trial. J Clin Oncol, 2012, 30(2): 134-141.
46. Elisei R, Schlumberger MJ, Müller SP, et al. Cabozantinib in progressive medullary thyroid cancer. J Clin Oncol, 2013, 31(29): 3639-3646.
47. Pappa T, Alevizaki M. Management of hereditary medullary thyroid carcinoma. Endocrine, 2016, 53(1): 7-17.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

The surgical treatment of medullary thyroid carcinoma

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