ENDOCRINE SURGERY - PART 2 docx

82. Marangos PJ, Gazdar AF, Carney DN. Neuron specific enolase in human small cell carcinoma cultures. Cancer Lett 1982; 15:67–71. 83. Carney DN, Marangos PJ, Ihde DC, Bunn PA, Cohen MH, Minna JD, Gazdar AF. Serum neuron-specific enolase: a marker for disease extent and response to therapy of small-cell lung cancer. Lancet 1982; 1:583– 585. 84. Jaques G, Bepler G, Holle R, Wolf M, Hannich T, Gropp C, Havemann K. Prognostic value of car- cinoembryonic antigen, neuron-specific enolase, and creatine kinase-BB levels in sera of patients with small lung cancer. Cancer 1988; 62:125–134. 85. Carney DN, Zweig MH, Ihde DC, Cohen MH, Makuch RW, Gazdar AF. Elevated serum creatine kinase BB levels in patients with small cell lung cancer. Cancer Res 1984; 44:5399–5403. 86. Baylin SB, Abeloff MD, Wieman KC, Tomford JW, Ettinger DS. Elevated histaminase (diamine oxidase) activity in small-cell carcinoma of the lung. N Engl J Med 1975; 293:1286–1290. 87. O’Connor DT, Deftos LJ. Secretion of chromogranin A by peptide-producing endocrine neoplasms. N Engl J Med 1986; 314:1145–1151. 88. Eriksson B, Arnberg H, Oberg K, Hallman U, Lundqvist G, Warnstedt C, Wilander E. A polyclonal antiserum against chromogranin A and B—a new sensitive marker for neuroendocrine tumours. Acta Endocrinol 1990; 122:145–155. 89. Liddle GW, Island DP, Ney RL, Nicholson WE, Shimuzu N. Nonpituitary neoplasms and Cushing’s syndrome. Arch Intern Med 1963; 111:471–475. 90. Baylin SB, Mendelsohn G. Ectopic (inappropriate) hormone production by tumors: mechanisms involved and the biological and clinical implications. Endocr Rev 1980; 1:45–77. 91. Silva OL, Becker KL, Primack A, Doppman JL, Snider RH. Ectopic production of calcitonin. Lancet 1973; 1:317. 92. Roos BA, Lindall AW, Baylin SB, O’Neil J, Frelinger AL, Birnbaum RS, Lambert PW. Plasma immunore- active calcitonin in lung cancer. Endocr Res Commun 1979; 6:169–190. 93. Wallach SR, Royston I, Taetle R, Wohl H, Deftos LJ. Plasma calcitonin as a marker of disease activity in patients with small cell carcinoma of the lung. J Clin Endocrinol Metab 1981; 53:602–606. 94. Becker KL, Silva OL, Gazdar AF, Snider RH, Moore CF. Calcitonin and small cell cancer of the lung. In: Becker KL, Gazdar AF, eds. The Endocrine Lung in Health and Disease. Philadelphia: Saunders, 1984; 528–548. 95. Silva OL, Becker KL, Primack A, Doppman JL, Snider RH. Ectopic secretion of calcitonin by oat cell carcinoma. N Engl J Med 1974; 290:1122–1124. 96. Yamaguchi K, Abe K, Adachi I, Kimura S, Suzuki M, Shimada A, Kodama T, Kameya T, Shimosato Y. Peptide hormone production in primary lung tumors. Rec Res Cancer Res 1985; 99:107–116. 97. Sano T, Saito H, Yamasaki R, Hamaguchi K, Ooiwa K, Shimoda T, Hosoi E, Saito S, Hizawa K. Immu- noreactive somatostatin and calcitonin in pulmonary neuroendocrine tumour. Cancer 1986; 57:64–68. 98. Silva OL, Broder LE, Doppmann JL, Snider RH, Moore CF, Cohen MH, Becker KL. Calcitonin as a marker for bronchogenic cancer. Cancer 1979; 44:680– 684. 99. Becker KL, Sil va OL, Snider RH, Moore CF, Geelhoed GW, Nash D. The pathophysiology of pulmonary calcitonin. In: Becker KL, Gazdar AF, eds. The Endocrine Lung in Health and Disease. Philadel- phia: Saunders, 1984;277–299. 100. Coates PJ, Doniach I, Howlett TA, Rees LH, Besser GM. Immunocytochemical study of 18 tumours causing ectopic Cushing’s syndrome. J Clin Pathol 1986; 39:955–960. 101. Del Gaudio A. Ectopic ACTH syndrome. Int Surg 1988; 73:44–49. 102. Ratcliffe JG. ACTH and related peptides in lung cancer. Rec Res Cancer Res 1985; 99:46–55. 103. White A, Clark AJ, Stewart MF. The synthesis of ACTH and related peptides by tumours. Clin Endo- crinol Metab 1990; 4:1–27. 104. Southgate HJ, Archibold GPR, El-Sayed ME, Wright J, Marks V. Ectopic release of GHRH and ACTH from an adenoid cystic carcinoma resulting in acro- megaly and complicated by pituitary infarction. Post- grad Med J 1988; 64:145–148. 105. Gewirtz G, Yalow RS. Ectopic ACTH production in carcinoma of the lung. J Clin Invest 1974; 53:1022– 1032. 106. Ayvazian LF, Schneider B, Gewirtz G, Yalow RS. Ectopic production of big ACTH in carcinoma of the lung: its clinical usefulness as a biologic marker. Am Rev Respir Dis 1975; 111:279–287. 107. Dupont AG, Somers G, VanSteirteghem AC, Watson F, Vanhaelst L. Ectopic adrenocorticotropin production: disappearance after removal of inflammatory tissue. J Clin Endocrinol Metab 1984; 58:654–658. 108. Thorne NA, Transbol I. Hyponatraemia and bronchogenic carcinoma associated with renal excretion of large amounts of antidiuretic material. Am J Med 1963; 35:257–268. 109. Bower BF, Mason DM, Forsham PH. Bronchogenic carcinoma with inappropriate antidiuretic activity in plasma and tumour. N Engl J Med 1964; 271:934–938. 110. Mu ¨ ller P, Quincke H. Untersuchungen u ¨ ber den Stoffwechsel bei Tuberkulose. Tuberkulose und Chlor- stoffwechsel II. Dtsch Arch Klin Med 1928; 160:24– 39. 111. Vorherr H, Massry SG, Fallet R, Kaplan L, Kleeman CR. Antidiuretic principal in tuberculous lung tissue The Neuroendocrine Lung 55 of a patient with pulmonary tuberculosis and hyponatraemia. Ann Int Med 1970; 72:383–387. 112. Hansen M, Hammer M, Hummer L. ACTH, ADH and calcitonin concentrations as markers of response and relapse in small cell carcinoma of the lung. Cancer 1980; 46:2062–2067. 113. Moertel CG. An odyssey in the land of small tumors. J Clin Oncol 1987; 5:1503–1522. 114. Feldmen JM. Carcinoid tumors and syndrome. Semin Oncol 1987; 14:237–246. 115. Lembeck F. 5-Hydroxytryptamine in a carcinoid tumour. Nature 1953; 172:910–911. 116. Brown WH. A case of pluriglandular syndrome: diabetes of bearded women. Lancet 1928; 2:1022–1023. 117. Cushing H. The basophil adenomas of the pituitary body and their clinical manifestations (pituitary baso- philism). Bull Johns Hopkins Hosp 1932; 50:137–195. 118. Winkler WA, Crankshaw OF. Chloride depletion in conditions other than Addison’s disease. J Clin Invest 1938; 17:1–6. 119. Schwartz WB, Bennett W, Curelop S, Bartter FC. A syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic hormone. Am J Med 1957; 23:529–542. 120. Bartter FC, Schwartz WB. The syndrome of inappropriate secretion of antidiuretic hormone. Am J Med 1967; 42:790–806. 121. Bayliss PH. Syndrome of inappropriate antidiuretic hormone secretion. In: Sheaves R, Jenkins PJ, Wass JAH, eds. Clinical Endocrine Oncology. Oxford: Blackwell Science, 1997;479–483. 122. Greco FA, Hainsworth J, Sismani A, Richardson RL, Hande JR, Oldham RK. Hormone production and paraneoplastic syndromes. In: Greco FA, Oldham RK, Bunn PA, eds. Small Cell Lung Cancer. New York: Grune and Stratton, 1981;177–223. 123. Rassam JW, Anderson G. Incidence of paramalignant disorders in bronchogenic carcinoma. Thorax 1975; 30:86–90. 124. Anderson G. Paramalignant syndromes in lung cancer. London: Heinemann, 1973. 125. Gammell JA. Erythema gyratum repens. Arch Der- matol 1952; 66:494–505. 126. Holt PJA, Davies MG. Erythema gyratum repens, an immunologically-mediated dermatosis. Br J Dermatol 1977; 96:343–347. 127. Fretzin DF. Malignant down. Arch Dermatol 1967; 95:294–297. 128. Barnes BE. Dermatomyositis and malignancy. A review of the literature. Ann Intern Med 1976; 84:68–76. 129. Cox NH, Lawrence CM, Langtry JAA, Ive FA. Dermatomyositis: disease associations and an evaluation of screening investigations for malignancy. Arch Dermatol 1990; 126:61–65. 130. Pankow W, Neumann K, V-Wichert P. Bronchial carcinoma associated with pulmonary osteoarthropathy (Marie-Bamberger disease). Pneumologie 1990; 44:1306–1311. 131. Pineda CJ, Guerra J, Weisman MH, Resnick D, Martinez-Lavin M. The skeletal manifestations of clubbing: a study in patients with cyanotic congenital heart disease and hypertrophic osteoarthropathy. Semin Arthritis Rheum 1985; 14:263–273. 132. Shneerson JM. Digital clubbing and hypertrophic osteoarthropathy: the underlying mechanisms. Br J Dis Chest 1981; 75:113–131. 133. Dickinson CJ, Martin JF. Megakaryocytes and platelet clumps as the cause of finger clubbing. Lancet 1987; 2:1434–1435. 134. Braegger CP, Corrigan CJ, MacDonald TT. Finger clubbing and tumour necrosis factor alpha. Lancet 1990; 336:759–760. 135. El-Salhy M, Simonsson M, Stenling R, Grimelius L. Recovery from Marie-Bamberger’s syndrome and diabetes insipidus after removal of a lung adenocarci- noma with neuroendocrine features. J Int Med 1998; 243:171–175. 136. Huckstep RL, Bodkin PE. Vagotomy in hypertrophic pulmonary osteoarthropathy associated with bronchial carcinoma. Lancet 1958; 2:343–345. 137. Anderson NE, Rosenblum MK, Graus F, Wiley RG, Posner JB. Autoantibodies in paraneoplastic syndromes associated with small-cell lung cancer. Neu- rology 1988; 38:1391–1398. 138. Dalmau J, Furneaux HM, Gralla RJ, Kris MG, Posner JB. Detection of the anti-Hu antibody in the serum of patients with small cell lung cancer. A quantitative Western blot analysis. Ann Neurol 1990; 27:544–552. 139. Furneaux HF, Reich L, Posner JB. Autoantibody synthesis in the central nervous system of patients with paraneoplastic syndromes. Neurology 1990; 40:1085– 1091. 140. Graus F, Elkon KB, Lloberes P, Ribalta T, Torres A, Ussetti P, Valls J, Obach J, Agusti-Vidal A. Neuronal antinuclear antibody (anti-Hu) in paraneoplastic encephalomyelitis simulating acute polyneuritis. Acta Neurol Scand 1987; 75:249–252. 141. Veilleux M, Bernier JP, Lamarche JB. Paraneoplastic encephalomyelitis and subacute dysautonomia due to an occult ayptical carcinoid tumour of the lung. Can J Neurol Sci 1990; 17:324–328. 142. Henson RA, Urich H. Cancer and the Nervous System: The Neurological Manifestations of Systemic Malignant Disease. Oxford: Blackwell, 1982. 143. Sawyer RA, Selhorst JB, Zimmerman LE, Hoyt WF. Blindness caused by photoreceptor degeneration as a remote effect of cancer. Am J Ophthalmol 1976; 81: 606–613. 144. Jacobson DM, Thirkill CE, Tipping SJ. A clinical triad to diagnose paraneoplastic retinopathy. Ann Neurol 1990; 28:162–167. 145. Boghen D, Sebag M, Michaud J. Paraneoplastic optic Gosney56 neuritis and encephalo-myelitis. Report of a case. Arch Neurol 1988; 45:353–356. 146. Albin RL, Bromberg MB, Penney JB, Knapp R. Chorea and dystonia: a remote effect of carcinoma. Move Disord 1988; 3:162–169. 147. Giordana MT, Soffietti R, Schiffer D. Paraneoplastic opsoclonus: a neuropathologic study of two cases. Clin Neuropathol 1989; 8:295–300. 148. Handforth A, Nag S, Sharp D, Robertson DM. Paraneoplastic subacute necrotic myelopathy. Can J Neurol Sci 1983; 10:204–207. 149. Brain WR, Croft PB, Wilkinson M. Motor neurone disease as a manifestation of neoplasm. Brain 1965; 88:478–500. 150. Croft PB, Urich H, Wilkinson M. Peripheral neuropathy of sensorimotor type associated with malignant disease. Brain 1967; 90:3–66. 151. Graus F, Elkon KB, Cordon-Cardo C, Posner JB. Sensory neuronopathy and small cell lung cancer: antineuronal antibody that also reacts with the tumor. Am J Med 1986; 80:45–52. 152. Park DM, Johnson RH, Crean GP, Robinson JF. Orthostatic hypotension in bronchial carcinoma. Br Med J 1972; 3:510–511. 153. Schuffler MD, Baird HW, Fleming CR, Bell CE, Bouldin TW, Malagelada JR, McGill DB, LeBauer SM, Abrams M, Love J. Intestinal pseudo-obstruction as the presenting manifestation of small cell carcinoma of the lung. Ann Intern Med 1983; 98:129–134. 154. Chinn JS, Schuffler MD. Paraneoplastic visceral neuropathy as a cause of severe gastrointestinal motor dysfunction. Gastroenterology 1988; 95:1279–1286. 155. Eaton LM, Lambert EH. Electromyography and electric stimulation of nerves in diseases of motor unit. Observations on myasthenic syndrome associated with malignant tumors. J Am Med Ass 1957; 163: 1117–1124. 156. Ferroir JP, Milleron B, Ropert A, Billy C, Nahum L, Tcherakian S, Carette MF. Atypical paraneoplastic myasthenic syndrome: Lambert-Eaton syndrome or myasthenia? Rev Pneumol Clin 1999; 55: 168–170. 157. Fukunaga H, Engel AG, Lang B, Newsom-Davis J, Vincent A. Passive transfer of Lambert-Eaton myasthenic syndrome with IgG from man to mouse depletes the presynaptic membrane active zones. Proc Natl Acad Sci USA 1983; 80:7636–7640. 158. Fukunaga H, Engel AG, Osame M, Lambert EH. Paucity and disorganization of presynaptic membrane active zones in the Lambert-Eaton myasthenic syndrome. Muscle Nerve 1982; 5:686–697. 159. Chester KA, Lang B, Gill J, Vincent A, Newsom- Davis J. Lambert-Eaton syndrome antibodies: reac- tion with membranes from a small cell lung cancer xenograft. J Neuroimmunol 1988; 18:97–104. 160. Sher E, Pandiella A, Clementi F. Voltage-operated calcium channels in small cell lung carcinoma cell lines: pharmacological, functional, and immunological properties. Cancer Res 1990; 50:3892–3896. The Neuroendocrine Lung 57 6 Surgery for Differentiated Thyroid Cancer Ashok Shaha Memorial Sloan–Kettering Cancer Institute and Cornell Medical School, New York, New York, U.S.A. Arthur E. Schwartz Mount Sinai School of Medicine, New York University, New York, New York, U.S.A. 1 INTRODUCTION Thyroid cancer is fascinating in many ways. The wide spectrum of aggressiveness is extraordinary, ranging from differentiated malignancies in which most patients live out close to their normal lifespan, to anaplastic varieties that are almost universally lethal. Among many unique features of differentiated thyroid cancer, two require special mention. Age is the most important prognostic factor. It is interesting to note that the mortality in patients with thyroid cancer in the younger age group is extremely low, while the mortality in elderly patients is quite high. There is no other human cancer that parallels this biologi cal behavior. This is the only cancer where age is included in the staging system. There is no Stage III and IV cancer in patients below the age of 45 (1–4). Another unique feat ure is that the presence of nodal metastasis has almost no prognostic bearing. This clinical behavior is not seen in any other malignancy. In the majority of cancers, the presence of nodal metastasis decreases the survival by almost 50%: in well-differentiated thyroid cancer, there is no apparent effect on outcome (5). Thyroid cancer is one of the most common endocrine neoplasms. M ost deaths are the result of medull ary or anaplastic thyroid tumors, rather than differentiated types. There appears to be a steadily increasing incidence in the United States, as well as an increased proportion of the disease in women; in the 1970s approximately 8000 new patients with thyroid cancer were seen, but the mortality remained steady at 1000 per year over the past two decades. In 2002 there were 20,700 new cases of thyroid cancer (15,800 women and 4900 men). During the same year there were 1300 deaths from thyroid malignancy (800 women and 500 men), suggesting that the prognosis is worse in men (6). The mortality of differentiated thyroid cancer remains low; most deaths are directly related to the high-risk group, generally elderly patients with poorly differentiated histology or locally aggressive tumors. There is considerable debate and controversy about the management of the disease. Although most patients with well-differentiated thyroid cancer do well, there is contention related to the extent of thyroidectomy and postoperative management. There are vigorous proponents of routine total thyroidectomy, whereas other authors recommend less than total thyroidectomy, depending on the prognostic factors and risk groups. Approximately 2000 new peer-reviewed papers are published every year on the subject of thyroid cancer, reporting a large worldwide experience. Most of these studi es are retrospective, with a substantial institu- 59 tional bias reflected in the conclusions. Prospective randomized studies, though strongly recommended by the American College of Surgeons Oncology Group, are difficult to undertake. The relatively benign course of the disease requires a large number of patients and a long duration of follow-up for a prospective randomized study. Hundahl et al. (2) recently reviewed the data from the National Cancer Data Base describing the de mographics of 53,856 patients seen over a period of 10 years from 1985 to 1995. Their review reports that during that period the incidence of papillary cancer was 78% while the incidence of follicular, medullary, and anaplastic thyroid malignancy is 13, 4, and 2%, respectively (Table 1). Our understanding of thyroi d cancer has improved considerably in the last two decades with various reports describing the prognostic factors and analysis of risk groups. Hay (7,8) from the Mayo Clinic and Cady (9– 11) from the Lahey Clinic have divided patients into low and high-risk groups. The mortality in the low-risk group was less than 2%, while the mortality i n the high-risk group was approximately 46%. Shaha et al. from Memorial Sloan-Kettering Cancer Center divided the patients into low, intermediate, and high-risk groups with mortalities of 1, 13, and 43%, respectively (1). 2 APPROACH TO THYROID NODULES It is almost always preferable to remove the entire thyroid lobe and isth mus than to perform an incisional biopsy or to remove a nodule; this is because of the difficulty of establishing a definitive diagnosis on frozen section (see Chapter xx). It is disheartening to receive a final diagnosis of malignancy several days after a frozen section has been reported to be benign—not an unusual occurrence. The surgeon who has initially performed only an incisional biopsy or partial lobectomy then faces the arduous task of excising the remainder of the lobe, with increased danger to the recurrent nerve and the parathyroid glands, as well as a higher incidence of local recurrence (12,13). It is far better to remove the entire lobe and isthmus at the initial procedure, eliminating the need to go back to a previously dissected area. If the opposite lobe later requires removal, the surgeon has a virgin field to explore and the best opportunity to preserve the parathyroid glands and the recurrent nerve. 3 SPREAD OF THYROID CANCER NODAL AND DISTANT METASTASIS The spread of thyroid cancer can be divided into local extension, cervical and mediastinal lymph node involve- ment, and distant metastasis (14,15). It is interesting to note that even with a small or occult primary tumor, particularly in the adolescent t o 30-year age group, there may be bulky neck node metastases, whereas in elderly patients it is not unusual to find a large primary tumor without palpable neck disease. Distant metastases, however, are more likely to be seen in advanced local disease or with massive nodal metastasis. The incidence of nodal meta stases ranges from 50 to 60%, while distant metastases are noted at the time of initial presentation in only 5% of patients. Most of the distant metastases, especially in papillary carcinoma, occur in the lungs. Follicular tumors may also present with disseminated metastases, especially to the bones of the pelvis and vertebral column (16,17). The incidence of clinically apparent neck node metastases in papillary thyroid cancer ranges from 15 to 50% (18). There is a rich lymphatic drainage from the thyroid gland with an extensive network of intraglandular lymphatics. Generally they follow the venous channels, with the first echelon nodes appearing in the tracheoesophageal groove. Subsequently, patients often develop enlarged lymph nodes in the jugular chain or in the superior mediastinum. In addition, differentiated thyroid cancer is known to spread to contralateral jugular lymph nodes in approximately 10% of cases. The lower jugular or Level IV nodes (see Fig. 6) are commonly involved in patients with well-differentiated thyroid cancer; the majority of lymph node metastases are seen in the paratracheal Table 1 Incidence and Survival of Histological Types of Thyroid Carcinoma Histological type Incidence, (1985–1990) (%) 10-Year overall survival (%) Papillary 77.9 93 Follicular 14.2 85 Hu ¨ rthle cell a 2.7 76 Medullary 3.7 75 Undifferentiated/ anaplastic b 1.6 14 a Although the survival of patients with Hu ¨ rthle cell carcinoma closely matched that of patients with follicular carcinoma at 5 years, survival at 10 years was 9% lower, suggesting a marginally worse prognosis. b In this report, the 14% survival of anaplastic and undifferentiated carcinoma does not discriminate between the two types. Classic anaplastic carcinoma (giant and spindle cell tumors) has a survival that is much worse than undifferentiated types. Source: Ref. 2. Shaha and Schwartz60 and jugular chains. Superior mediastinal nodes are also frequently involved. Level I lymph nodes (in the submandibular and submental area), however, are rarely affected in differentiated thyroid cancer, with an incidence of less than 3% (19–24). 4 EVALUATING RISK GROUPS IN DIFFERENTIATED THYROID CANCER Before making any decisions regarding the extent of thyroidectomy, it is valuable to understand the prognostic factors and risk groups in thyroid cancer. The European Organization for Research on Treatment of Cancer (EORTC) initially defined variables such as age, sex, histological type, extrathyroidal extension, and distant metastasis in their report in 1979. A complicated scoring system was addressed in this review (25). Many prognostic systems are available, but essen- tially they all relate to the above features. Understand- ing the components of these indicators is important in the overall management of differentiated thyroid cancer. Other prognostic factors such as DNA ploidy, p53 mutation, EGF receptor, and adenylate cyclase activity are reported, but these molecular prognostic factors are not useful in clinical practice at this time. Hay et al. from the Mayo Clinic defined the prognostic factors as AGES—age, grade of tumor, extrathyroidal e xtension, and size of tumor (2,26). The grade of the tumor was difficult to interpret at many other in- stitutions; Cady et al. from the Lahey Clinic defined the prognostic factors as AMES—age, distant metastasis, extrathyroidal extension, and size of the tumor (9–11). The Mayo Clinic revisited the prognostic factors and defined the new system as MACIS—metastasis, age, completeness of resection, local invasion, an d size of the tumor (27). Completeness of resection is a critical prognostic factor; the goal of any surgical procedure should be to remove all gross tumor. Based on these prognostic factors, the Mayo Clinic and the Lahey Clinic divided the patients into low- and high-risk groups. The reviewers from Memorial Sloan-Kettering Can- cer Center formulated prognostic factors based on patient-related and tumor-related factors, dividing their patients into low, intermediate, and high-risk groups. The low-risk group included patients under the age of 45 with low-risk tumors, while the high-risk group included patients above the age of 45 with high-risk tumor. The intermediate-risk group was divided into two categories: young patients with aggressive tumors or older patients with less aggressive tumors. Long-term survival in the low, intermediate, and high-risk groups was reported to be 99 , 87, and 57%, respectively. Interestingly, when these data were reviewed for the patients in the low risk-group who died, it was found that all four had had aggressive histolological features that were not initially reported (28–30). These prognostic scoring systems are critical to surgeons who selectively employ lobectomy or total thyroidectomy for the management of differentiated cancer. For others who routinely perform total or near-total thyroidectomy without regard to risk group criteria, they offer a valuable prognostic indicator and the opportunity to evaluate the results of treatment. 5 PAPILLARY CARCINOMA Papillary, papillary-follicular carcinoma, and papillary variant of follicular carcinoma comprise about 85% of differentiated thyroid cancer and share the same prognosis (31–33). The realization that the follicular variant of papillary carcinoma is a form of papillary carcinoma rather than a follicular cancer, which has a less favorable outlook, explains the erroneously better cure rates for follicular cancer in the older literatu re. Other rarer types of papillary carcinoma such as tall cell, insular, diffusely sclero tic, and columnar cell are more aggressive and usually present at a higher stage. Papillary cancers characteristically spread to neck nodes and at times to the lungs. Neck node metastases generally do not affect survival. The most critical prognostic feature is the age of the patient; those who are over 45 have a much poorer outlook than those who are younger. Small papillary carcinomas ( V1 cm), sometimes referred to as ‘‘occult’’ or microcarcinoma, have an excellent prognosis, but the outcome becomes worse as the size of the primary tumor increases; those >4 cm. in diameter have a distinctly decreased survival (34, 35). Extension of the tumor beyond the ca psule of the thyroid, invasion of adjacent tissues, or distant metastases are adverse factors in the overall cure rates (36–38). 6 FOLLICULAR CARCINOMA These tumors are less frequent than the papillary type, comprising approximately 15% of thyroid cancers, and have a less favorable prognosis (39–41). The incidence increases in iodine-deficient areas. There is no evidence that benign follicul ar adenomas develop into cancer. The overwhelming proportion are nonfunctional and appear cold on radioactive scan. Surgery for Differentiated Thyroid Cancer 61 Follicular cancers are less likely to spread to regional lymph nodes and have a higher incidence of distant metastases than papillary cancer. Metastases presenting at the time of diagnosis portend a poor outlook; bone and lungs are the most frequent sites. The Hu ¨ rthle cell variant has been of special interest, with some authorities finding that they are more likely to metastasize, exhibit a more aggressive behavior, and have a decreased survival. This has been challenged by others who state that stage for stage they have the same outlook as other follicular cancers. In a recent study it was noted that, unlike other differentiated thyroid cancers, nodal metastases augur a worse outcome (42–47 ). 7 EXTENT OF SURGERY FOR DIFFERENTIATED THYROID CANCER Microscopic cancer that does not influence the outcome of the disease is an important factor in the management of differentiated thyroid cancer. The issue is whether or not it should be surgically removed. After years of contention it is now almost universally accep- ted that neck dissection is not indicated in patients with clinically negative nodes—even though a high percent- age are positive on microscopic evaluation. Contro- versy remains in regard to the extent of thyroidectomy required for differentiated thyroid cancer in relation to its frequent microscopic presence in the opposite lobe (30–50%). The major indications for total thyroidectomy include high-risk patients with high-risk tumors, young patients with bulky nodal metastasis, patients with gross disease in both lobes of the thyroid, major extrathyroidal extension, or a preoperative diagnosis of poorly differentiated thyroid cancer (48). A thyroid malignancy in a patient with a history of radiation to the neck is also an indication for total thyroidectomy because of the risk of developing disease in the opposite lobe. Patients who present initially with distant metastasis are advised to undergo total thyroidectomy to facilitate radioactive iodine ablation. Authors who advocate routine use of total thyroidectomy point to the following (49): 1. The high incidence of microscopic disease in the opposite lobe (40–70%). Although clinical recurrence is 5% or less, it can be reduced by total thyroidectomy. 2. Total th yroidectomy permit s ablation of all thyroid tissue, increasing the sensitivity of early detection of pulmonary metastasis or other metastatic disease by radioactive iodine and monitoring with serum thyroglobulin levels. The location of metastatic disease and its treatment by RAI ablation becomes easier. 3. It removes the minimal possibility that anaplastic or poorly differentiated thyroid cancer could develop in the thyroid remnant. 4. Although many authors advocate a decision on whether to perform total thyroidectomy or lobectomy by the use of staging systems that define- high and low-risk categories, these clas- sifications are postoperative evaluations. Factors such as aggressive tumor pathology or the extent of local tissue invasion are not available pre- operatively. Distant metastases may not be apparent until postoperative radioactive iodine studies or thyroglobulin levels reveal them (50). Wong (51) states that when patients are treated by total or near-total thyroidectomy with postoperative radioiodine, the ‘‘benefit of improved survival is similar to that obtained by not smoking, or surgery for three- vessel coronary artery disease.’’ In a report on optimal treatment strategy in patients with papillary thyroid cancer, Esnaola et al. from the M.D. Anderson Cancer Center report that total thyroidectomy maximizes life expectancy in low as well as high-risk patients (31). Mazzaferri et al. advise that all patients with follicular carcinoma should have total thyroidectomy to facilitate postoperative ra dioiodine therapy, noting that most deaths are due to distant metastases (39). Others disagree, finding survival rates in low-risk patients with differentiated thyroid carcinoma essen- tially the same, whether treated by lobectomy or total thyroidectomy. There is general agreement, however, that high-risk patients or those who present with distant metastases should have total thyroidectomy and radioiodine ablation. The proponents of les s than total thyroidectomy appreciate these logical points, but they base their treatment philosophy on the risk group analysis. The long-term results in the low-risk group are a survival of 99%; routine total thyroidectomy in this group does not appear to be warranted. The major argument for total thyroidectomy is the presence of microscopic disease in the opposite lobe, but the clinical appearance of recurrent disease in the opposite lobe is less than 5%. Multi- centric microscopic disease is considered a ‘‘laboratory cancer’’ with no significant prognostic implication. Authors who favor hemithyroidectomy for low-risk cancer state that a minority of patients will require postoperative radioactive iodine. This would represent Shaha and Schwartz62 patients in the high-risk group, those with locally aggressive tumors, or poorly differentiated histology. These authors feel that for a patient presenting with a solitary thyroid nodule less than 1–1.5 cm in diameter and no other adverse features, lobectomy and isthmu- sectomy is effective treatment and usually the maximum surgical procedure necessary. Routine application of total thyroidectomy in every patient presenting with solitary thyroid nodule is probably unnecessary (1,48). 8 TECHNIQUE OF THYROIDECTOMY The complications of thyroid surgery are directly related to the extent of surgery and inversely propor- tional to the experience of the operating surgeon. Total thyroidectomy would be the treatment of choice for all primary thyroid malignancy if it were not for the risk of hypoparathyroidism and recurrent nerve injury. It offers the advantage of removing the prim ary lesion and all foci of malignant tissue within the thyroid gland. The elimination of the total thyroid parenchyma (which might require radioactive iodine ablation of any remnant) would enable the physician to monitor the patient for recurrence with radioactive iodine scanning and serum thyroglobulin levels. In practice, the benefits of total thyroidectomy mu st be weighed against a risk of permanent hypoparathyroidism ranging up to 4–5% and the hazard of recurrent nerve injury of 1–3%. The usual extended course and good prognosis of well-differentiated thyroid carcinoma makes it difficult to select those patients who warrant the risk of total thyroidectomy. The initial approach for the surgery of differentiated thyroid carcinoma is total lobectomy on the side of the lesion with resection of the isthmus and pyramidal lobe. We emphasize visualization of the recurrent nerve and parathyroid glands. With experience it becomes possible to identify them and preserve their blood supply. Careful hemostasis is needed so that the distinctive appearance of the parathyroid glands will not be altered. The normal parathyroid is bean shaped, 3–6 mm. This is in marked contrast to the globular, oval or rounded appearance of a lymph node. The color is a dark yellow, tan, or brownish hue, different from the lighter yellow color of fat, or the darker gray, pink, or varying flesh tones of lymph nodes. It is usually cradled in a fat pad creating a distinctive combination. As the gland is manipulated, its color becomes darker because of vascular impairment, a feature not found with fat or lymph nodes. The thyroid incision is placed transversely across the neck below the cricoid and at least two fingerbreadths above the sternal notch (Fig. 1). Many surgeons outline the incision by placing a suture across a crease line in the neck, creating pressure, and then making the incision in the depressed line. We prefer to carefully mark the midline and draw a line across the neck at a level that is measured and marked by a pen. A slightly upward curve is desirable. This has proved more pre- dictable for us than the string method. The use of a natural crease line in the neck is attractive if the line is horizontal, but if the natural line is oblique, such an incision becomes unsightly. A higher location in the neck produces a more pleasing appearance; an incision close to the sternum tends to spread. A position closer to the cricoid cartilage makes dissection of the upper portion of the recurrent laryngeal nerve easier than a lower one because of better exposure in the area where the nerve ascends below the cricothyroid muscle. A more superiorly placed incision also facilitates a cos- metic extension of the wound laterally and upward, should a neck dissection be required. Recently we have used the ‘‘harmonic scalpel,’’ an ultrasonic knife that seals as it cuts, as an adjunct in the performance of thyroidectomy. This instrument makes it possible to divide tissue without the need for ligatures. It is useful in dividing the superior pole vessels, transecting the ima vessels, and dividing the Figure 1 Placement of thyroid incision. Surgery for Differentiated Thyroid Cancer 63 thyroid isthmus a s the gland is separated from the trachea. Other portions of the operation are performed with traditional instrument s. A key to facile and elegant neck and thyroid surgery is to take advantage of tissue planes of the deep cervical fascia. Elevating the superior and inferior flaps is almost bloodless if the layer just beneath the platysma is followed and dissected. The strap muscles, which are enclosed by the cervical fascia, can be cleanly separated from the thyroid by identifying this investing layer. The larynx, thyroid, trachea, pharynx, and esophagus are contained within separate compartments. A fascial layer also encloses the thyroid gland, facilitating its mobilization. The parathyroid glands have their own separately derived capsules that ease their separation from the thyroid. Good exposure is obtained by separating the strap muscles in the midline and retracting them laterally. Transverse division of the medial portion of the sternohyoid muscle near its insertion provides marked additional increase in access. Since the muscles form an ‘‘A’’ shape, the additional incision at the narrowed space between their upper portions offers a geometric increase in visibility. The sternothyroid muscle is routinely divided completely for better visibility (Fig. 2). If the tumor is large or inaccessible, there should be no hesitation to completely divide the strap muscles transversely at their lower third. At the end of the procedure sternohyoid muscles are repaired. We have found it unnecessary to reapproximate the sternothy- roids. If the strap muscles are adherent to the thyroid gland, especially to the tumor, they are resected with the gland. It is not unusual for malignant disease of the thyroid to penetrate the musculature. After the thyroid gland is exposed, the middle thyroid vein is divided. This vessel drains directly into the jugular vein; failure to liga te it securely may risk hem- orrhage that would make it more difficult to identify the parathyroid glands and recurrent nerve. It is then possible to mobilize the thyroid lobe—often by blunt dissection. The next goal is the division of the upper pole vessels. The thyroid lobe is first retracted downward and laterally to expose the superior pole vessels. Visualizing the cricothyroid muscle is the key to safe dissection of the upper pole. It is often helpful to divide the cricothyroid branch of the superior thyroid artery to gain access to the space between the cricothyroid muscle and upper pole vessels (Fig. 2). By clearing this space and placing a curved clamp from medial to lateral beneath the upper pole vessels, it is possible to avoid injury to the cricothyroid muscle’s close companions: the superior and recurrent laryngeal nerves. The superior lary ngeal nerve, which may be close to the vessels or even accompany them, is best preserved by awareness of its presence, isolating and dividing the superior pole vessels individ- ually close to the upper pole of the thyroid. Sometimes the nerve can be seen as it descends with the vessels and on to the cricoid muscle, but usually it is not visualized (Fig. 3). A recent study showed that identification and dissection of the superior laryngeal nerve offered no better protection from damage than simply transecting the superior vessels close to the thyroid (52). We prefer to divide the superior pole vessels initially because it increases the mobility of the thyroid lobe, facilitating exposure of the parathyroid glands and recurr ent nerve. Rotating the thyroid lobe medially and pulling it upward stretches the nerve, aiding in its identification and dissection. It also makes it easier to look for a superior pa rathyroid gland or a suggestive fat pad posterior and lateral to the upper pole (Fig. 3). When not present in its classic position, it is often located lower, close to the main trunk of the superior thyroid artery, or a centimeter or so above the inferior thyroid Figure 2 Exposure of the thyroid gland. The medial third of the sternohyoid muscle has been divided to provide greater access to the thyroid gland, particularly the upper pole. Transection of the sternothyroid muscle, as diagrammed, will offer direct and easy access of the thyroid lobe and the superior pole vessels. Division of the cricoid branch of the superior thyroid artery offers increased exposure to the space between the cricothyroideus and the superior pole of the thyroid. (From Ref. 13.) Shaha and Schwartz64 [...]... receptors in mice Thyroid 20 00; 10(1):41– 52 Wikstrom L, Johansson C, Salto C, et al Abnormal heart rate and body temperature in mice lacking thyroid hormone receptor alpha 1 EMBO J 1998; 17 (2) :455– 461 Weiss RE, Refetoff S Resistance to thyroid hormone Rev Endocr Metab Disord 20 00; 1(1 2) :97–108 Arafah BM Increased need for thyroxine in women 19 20 21 22 23 24 25 26 27 28 29 30 31 with hypothyroidism... 122 :464–471 Noguchi S, Murakami N The value of lymph-node dissection in patients with differentiated thyroid cancer Surg Clin North Am 1987; 67 :25 1 26 1 Scheumann GF, Gimm O, Wegener G, et al Prognostic significance and surgical management of locoregional lymph node metastases in papillary thyroid cancer World J Surg 1994; 18:359–367 Noguchi S, Noguchi A, Murakami N Papillary 73 22 23 24 25 26 27 28 29 ... study of 535 cases observed in a 50-year period Surgery 19 92; (1 12) :1139–1147 Czaja JM, McCaffrey TV The surgical management of laryngotracheal invasion by well-differentiated papillary thyroid carcinoma Arch Otolaryngol Head Neck Surg 1997; ( 123 ):484–490 74 37 Grillo HC, Zannini P Resectional management of airway invasion by thyroid carcinoma Ann Thorac Surg 1986; ( 42) :28 7 29 8 38 McCaffrey TV, Bergstralh... a nonthreatening malignancy Surgery 19 92; (1 12) :1130–1136 42 Stojadinvic A, Ghossein RA, Hoos A, et al Hurthle cell carcinoma: a critical histopathid appraisal J Clin Oncol 20 01; 19(10) :26 16 26 25 43 Rosai J, Carcangiu ML, DeLellis RA Tumors of the Thyroid Gland Atlas of Tumor Pathology Third Series, Vol 5, Fascicle 5 Washington, DC: Armed Forces Institute of Pathology, 19 92 44 Thompson NW, Dunn EL,... 19 20 21 lymph node metastasis in differentiated carcinoma of the thyroid—a matched pair analysis Head Neck 1996; 18: 127 –1 32 Jemal A, Thomas T, Murray M Cancer statistics CA 20 02; 52( 1) :23 –47 Hay ID, Grant CS, Taylor WF, et al Ipsilateral lobectomy versus bilateral lobar resection in papillary thyroid carcinoma: a retrospective analysis of surgical outcome using a novel prognostic scoring system Surgery. .. receptor (TSH-R) expressed in mamalian cell lines to assay TSH-R autoantibodies Mol Cell Endocrinol 1990; 73:R13–R18 Camacho PM, Dwarkanathan AA Sick euthyroid syndrome What to do when thyroid function tests are abnormal in critically ill patients Postgrad Med 1999; 105(4) :21 5 21 9 Griffin JE The thyroid In: Griffin JE, Ojeda SR, eds Textbook of Endocrine Physiology New York: Oxford, 19 92: 224 24 6 Falk SA... Engl J Med 20 01; 344 (23 ):1743–1749 Midgley JE Direct and indirect free thyroxine assay methods: theory and practice Clin Chem 20 01; 47(8): 1353–1363 Spencer CA, Takeuchi M, Kazarosyan M Current status and performance goals for serum thyroglobulin assays Clin Chem 1996; 42( 1):164–173 Stockigt JR Free thyroid hormone measurement A critical appraisal Endocrinol Metab Clin North Am 20 01; 30 (2) :26 5 28 9 McGregor... carcinoma of the thyroid Am J Surg 1996; 1 72( 6):6 92 694 Shaha AR, Clark OH, Goepfert H, Kaplan EL, Loree TR, Udelsman EL Symposium Part 2: therapy Current concepts in the management of thyroid cancer Contemp Surg 20 00; 56 (2) :105–118 Shaha AR, Shah JP, Loree TR Low-risk differentiated thyroid cancer: the need for selective treatment Ann Surg Oncol 1997; 4(4): 328 –333 Esnaola NF, Cantor SB, Sherman SI,... Toxicol Endocrinol 1999; 122 (1):13 20 Lamas L, Anderson PC, Fox JW, Dunn JT Concensus sequences for early iodination and hormonogenesis in human thyroglobulin J Biol Chem 1989; 26 4:13541– 13545 Dunn JT, Dunn AD Update on intrathyroidal iodine metabolism Thyroid 20 01; 11(5):407–414 Yen PM Physiological and molecular basis of thyroid hormone action Physiol Rev 20 01; 81(3):1097– 11 42 Forrest D, Vennstrom... 1990; 23 : 441–4 52 46 Carcangiu ML, Bianchi S, Savino D, et al Follicular Hurthle cell tumors of the thyroid Cancer 1991; 68: ¨ 1944–1953 47 Grant CS, Barr D, Goellner JR, et al Benign Hurthle ¨ Shaha and Schwartz 48 49 50 51 52 53 54 55 cell tumors of the thyroid: a diagnosis to be trusted? World J Surg 1988; 12: 488–495 Shaha AR Thyroid cancer: extent of thyroidectomy Cancer Control 20 00; 7(3) :24 0 24 5 . Lembeck F. 5-Hydroxytryptamine in a carcinoid tumour. Nature 1953; 1 72: 910–911. 116. Brown WH. A case of pluriglandular syndrome: diabetes of bearded women. Lancet 1 928 ; 2: 1 022 –1 023 . 117. Cushing. 100,000 thyroidectomies performed, 94 deaths secondary to postoperative bleeding could be prevented by a 24 -hour hospitalization com- pared to a 6-hour observation ( 12) . 12. 2 Recurrent Laryngeal. of antidiuretic hormone. Am J Med 1957; 23 : 529 –5 42. 120 . Bartter FC, Schwartz WB. The syndrome of inappropriate secretion of antidiuretic hormone. Am J Med 1967; 42: 790–806. 121 . Bayliss PH. Syndrome of