1. 12 th G. Rainey Williams Surgical Symposium What Operation for Thyroid Cancer? Ronald Squires, MD FACS Associate Professor of Surgery Sections of General and Transplant Surgery University of Oklahoma Health Science Center

2. RAS TOTAL THYROIDECTOMY

3. RAS Questions?

4. RAS Introduction n First reports of thyroidectomy from School of Salerno in Italy in 1170 n Johann Dieffenbach of Berlin in 1848 stated that thyroidectomy was “one of the most thankless and most perilous undertakings” in surgery n Outcomes were so poor that the French Academy of Medicine banned its practice in 1850 n Billroth performed 59 thyroidectomies from 1861-1867 with a 40% mortality—a later series from 1877-1881 reported 16 thyroidectomies with 100% survival n Theodore Kocher won the Nobel prize in medicine in 1909 for his contributions to thyroid surgery including many of the techniques still used by modern day thyroid surgeons n Halsted first to advocate and popularize subtotal thyroidectomy to preserve parathyroids and protect recurrent laryngeal nerves

5. RAS Thyroid Cancers n Differentiated cancers Papillary carcinoma Papillary carcinoma Mixed papillary/follicular carcinoma Mixed papillary/follicular carcinoma Follicular carcinoma Follicular carcinoma Hürthle cell Hürthle cell n Medullary carcinoma n Anaplastic carcinoma n Lymphoma of thyroid

6. RAS Thyroid Cancers n Differentiated cancers Papillary carcinoma Papillary carcinoma Mixed papillary/follicular carcinoma Mixed papillary/follicular carcinoma Follicular carcinoma Follicular carcinoma Hürthle cell Hürthle cell n Medullary carcinoma

7. RAS Thyroid Nodule Workup n 50% of population over 50 years have an US detectable thyroid nodule n Prevalence of nonpalpable clinically significant (1-1.5cm) nodes is 2-3% n 90% of all nodules reflect benign disease n Of the 10% of malignant nodules, 75% are papillary and 15% are follicular

8. RAS Thyroid Nodule Workup n Check TSH level If high, begin thyroid replacement until euthyroid If high, begin thyroid replacement until euthyroid If low, nuclear scan to check for hyperfunctioning nodule (very rarely malignant) If low, nuclear scan to check for hyperfunctioning nodule (very rarely malignant) n FNA with or without US guidance when euthyroid n Nodules greater than 1cm in two dimensions are clinically significant n 16% of patients with palpable nodules will have no nodule visible by US and the vast majority will be diagnosed with Hashimoto’s thyroiditis n In multinodular goiter, masses > 1cm should be biopsied (5-13% risk of cancer in these larger lesions)

9. RAS Thyroid Nodule Workup n FNA results should be limited Benign goiter Benign goiter Malignancy Malignancy Follicular neoplasm Follicular neoplasm Nondiagnostic sample Nondiagnostic sample n Diagnostic accuracy Sensitivity > 92% Sensitivity > 92% Specificity 91-98% Specificity 91-98%

10. RAS Thyroid Nodule Workup n Benign diagnosis Reultrasound in 6 months Reultrasound in 6 months – If same or smaller, follow yearly – If larger, (15% increase in size in two dimensions) then repeat FNA n Indeterminate diagnosis Repeat FNA in 3 months or consider using US guidance if not previously used Repeat FNA in 3 months or consider using US guidance if not previously used n Follicular cytology (80% benign disease) Thyroid scan (if “hot” nodule in euthyroid patient then observe) Thyroid scan (if “hot” nodule in euthyroid patient then observe) All cold nodules and hot nodules in hyperthyroid patients should be removed All cold nodules and hot nodules in hyperthyroid patients should be removed

11. RAS The Science n All recommendations are based on retrospective series or multivariate analysis n Mathematical models are also utilized to extrapolate data to existing populations n The incidence of thyroid carcinoma is 11,000 cases per year in the US with 1,100 deaths n Given the good overall survival, a prospective study would need at least 12,000 patients followed for a minimum of 20 years to distinguish subtle therapeutic differences

12. RAS Arguments for Total Thyroidectomy n Radioactive iodine may be used to detect and treat residual normal thyroid tissue and local or distant metastases n Serum thyroglobulin level is a more sensitive marker for persistent or recurrent disease when all normal thyroid tissue is removed n In up to 85% of papillary cancer, microscopic foci are present in the contralateral lobe. Total thyroidectomy removes these possible sites of recurrence n Recurrence develops in 7% of contralateral lobes (1/3 die) n Risk (though very low [1%]) of dedifferentiation into anaplastic thyroid cancer is reduced n Survival is improved if papillary cancer greater than 1.5cm or follicular greater than 1cm n Need for reoperative surgery associated with higher risk is lower

13. RAS Arguments against total thyroidectomy n Total thyroidectomy may be associated with higher complication rate than lobectomy n 50% of recurrences can be controlled with surgery n Fewer than 5% of recurrences occur in the thyroid bed n Tumor multicentricity has little clinical significance n Prognosis of low risk patients (age, grade, extent, size) is excellent regardless of extent of resection

14. RAS Complications n Hypoparathyroidism should occur in less than 2% of patients n Recurrent laryngeal nerve injury in virgin neck less than 0.5% of patients n Superior laryngeal nerve injury in virgin neck less than 2% of patients

15. RAS Papillary Carcinoma Algorithm for Treatment of Possible PTC

16. RAS Papillary Carcinoma n If FNA is suspicious for papillary ca but not diagnostic then incidence is 54% cancer n Presence of microcalcifications on FNA suggestive of papillary ca (36% sensitivity, 93% specificity, 76% accuracy) n Pts with confirmed or highly suspicious intraoperative finding should receive total or near total thyroidectomy (< 3 gm remnant) n Prophylactic node dissection not indicated

17. RAS Papillary/Differentiated Carcinoma n Up to 80% of patients found to have asymptomatic positive nodes during series of prophylactic neck dissections 1,2 n Clinically significant disease only develops in less than 10% of patients with microscopic lymph node metastases 1,3,4 n Central node dissection should be carried out if central nodes are enlarged and positive by frozen section n Ipsilateral modified neck dissection has been shown to reduce regional recurrence without improving survival if enlarged cervical node is positive by preop FNA or intraoperative frozen 5 Node Dissection: 1 Am J Surg 122:464-471,1971 2 World J Surg 18:359-367,1994. 3 Surg Clin North Am 67:251-261,1987. 4 Cancer 26:1053-1060, 1970 5 Textbook of Endocrine Surgery, WB Saunders, 1997, p90.

18. RAS Follicular Neoplasms n 14-29% are invasive cancer n Frozen section analysis can be misleading n Hallmarks of cancer are capsular or vascular invasion n Follicular CA more likely hematogenous spread n Worse prognosis associated with increased age and stage at diagnosis compared to papillary n >4cm nodule is 50-60% likely invasive disease

19. RAS Follicular Neoplasms n Resection of lobe/isthmus with careful examination for gross invasion or nodal disease n Await final pathology of lobe/isthmus and if positive, return to OR for completion lobectomy n Subsequent I 131 treatment, TSH suppression and monitoring of thyroglobulin (<2µg/l)

20. RAS Hürthle Cell Neoplasms n More aggressive than other differentiated thyroid carcinomas (higher mets/lower survival rates) n Decreased affinity for I 131 n Need to differentiate from benign/malignant n Cancer in 13-35% of Hürthle cell FNAs n 65% of tumors > 4cm are malignant n If malignant, needs total thyroidectomy and I 131 with thyroglobulin assays n Mets may be more sensitive to I 131 than primary

21. RAS Medullary Carcinoma n Presents as either an inherited syndrome (20%) or as an incidental event n More aggressive than the differentiated thyroid cancers n Does not respond to I 131 n Multicentric in 20% of sporadic cases and in almost all of inherited cases n Much more likely to invade lateral lymph basins n Need baseline CEA and calcitonin levels

22. RAS Medullary Carcinoma n Familial cases positive for RET proto- oncogene mutation n If positive family history, then genetic testing n If MEN IIA or FMTC then total thyroidectomy and central lymph node dissection between ages of 5-6 years n If MEN IIB then total thyroidectomy and central node dissection ages 6mos - 3 years n SURGERY IS ONLY EFFECTIVE THERAPY

23. RAS Medullary Carcinoma n If persistent elevated CEA or calcitonin, CT scan for residual disease (50% of pts) n Aggressive neck dissection advocated by many if persistent disease n Consider laparotomy for possible liver mets n Prolonged survival with significant symptoms not uncommon with widely metastatic disease

24. RAS Medullary Carcinoma

25. RAS Incidentaloma/Micrometastatic Disease n Lesions detected by imaging or found after surgery for unrelated indication n Thyroid nodules common in population (4- 10% have palpable nodules any given time) n Female/male incidence 6.4 / 1.6% n 12% detected by palpation vs. 45% by imaging n Lesions less than 1 cm-observe n Lesions 1-2cm “gray zone” n Lesions > 2cm are NOT INCIDENTAL

26. RAS Incidentaloma/Micrometastatic Disease n Consider suspicious features: Increased vascularity Increased vascularity Irregular margin Irregular margin Central microcalcification Central microcalcification Cervical adenopathy Cervical adenopathy

27. RAS Incidentaloma/Micrometastatic Disease

28. RAS Local Invasion of the Neck Tracheal resection repaired primarily

29. RAS Local Invasion of the Neck Crycoid invasion with local muscle flap reconstruction

30. RAS Local Invasion of the Neck Vertical hemilaryngectomy

31. RAS Local Invasion of the Neck Circumferential tracheal resection with primary anastomosis

32. RAS Summary n Total thyroidectomy is surgery of choice for differentiated cancer as well as medullary carcinoma of thyroid n Consider subtotal (less than 2gms residual tissue) if less experienced or hazardous operative environment n No therapeutic advantage for total thyroidectomy in setting of papillary microcarcinoma

33. RASQuestions