ENDOCRINE SURGERY - PART 3 pps

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Role of Ultrafast Papanicolaou-stained scrape preparations as an ad- junct to frozen sections in the surgical management of thyroid lesions. Endocr Pract 2001; 7:89–94. 108. Yang GC, Greenebaum E. Clear nuclei of papillary thyroid carcinoma conspicuous in fine-needle aspiration and intraoperative smears processed by Ultra- fast Papanicolaou stain. Mod Pathol 1997; 10:552– 555. Diagnosis and Management of Thyroid Nodules 131 11 Mediastinal Goiter Ashok Shaha Memorial Sloan–Kettering Cancer Institute and Cornell Medical School, New York, New York, U.S.A. 1 INTRODUCTION The management of mediastinal goiters is engrossing because of the complexity of surgical procedures and associated risks. Most frequently, surgery is advised to avoid problems related to airway, venous obstruction, and to rule out malignancy (1–7). The etiology of thyroid adenomas remains unclear. In normal glands some areas of the follicles are more active than others in conc entrating iodine and, pre- sumably, in secreting thyroid hormones. This may be secondary to differences in cell response to thyro id- stimulating hormone (TSH) . Variations occur in the frequency of mitoses within the same follicle. This follicular heterogeneity implies that clones of cells may divide at a higher rate than the remaining follicular cells and may give rise to adenomatous areas of growth (8). The most common cause of goiter is iodine defi- ciency, usually seen in third world countries; it is one of the most common problems in mountainous regions such as the Alps and the Himalayas (8,9). Iodine defi- ciency, resulting in increased TSH output in an attempt to maintain the euthyroid state, is often associated with large multinodular goiters rather than a homogeneous expansion of all thyroid follicular cells. The incidence of goiter (colloid or endemic) is rare in the United States because of the compulsory use of iodized salt. Thyroid tumors, of course, develop in the neck but can extend downw ard into the mediastinal region as they grow. Most enlarge over a long period of time and some occasionally remain asymptomatic. When symptoms are present, the most common are difficulty in breathing and an accompanying neck mass . The tumor may be almost entirely substernal at times, with no significant mass appearing in the neck. As a result of the bony confines of the thoracic inlet, mediastinal goiters lead to compression symptoms—mainly related to the trachea and esophagus but also at times produc- ing venous obstruction (10,11). Klein, a German surgeon, first reported in 1820 removal of a substernal goiter. The mortality from thyroid surgery before the Kocher era was almost 40%. Credit goes to Kocher, Halsted, and Lahey for perfect- ing the technique of thyroid surgery. As late as 1866, Samuel Gross from the University of Pennsylvania remarked that thyroid surgery was ‘‘butchery’’ and that ‘‘no honest and sensible surgeon would ever engage in thyroid surgery.’’ Clearly, this was an era before anti- sepsis, hemostats, and the use of iodine to control hyperthyroidism! Kocher, with his vast experience in thyroid surgery, studied the physiology, improved the techniques of thyroid surgery, and was the first surgeon to receive the Nobel Prize for his contributions in thyroid diseases (12). 2 DEFINITION There are several theories regarding substernal goiter, but the most popular is that the goiter represents an 133 inferior growth from the cervical thyroid gland that is supplied by the vessels in the neck. The upright posture of human beings combined with normal swallowing and breathing mechanisms induce negative intrathoracic pressure. The weight of the enlarging mass allows the gland to grow and descend through the thoracic inlet into the substernal position. Inferiorly there is no ana- tomical structure that can restrict the growth of the thyroid gland. This leads to the path of least resist- ance—towards the thoracic inlet. 3 CLINICAL PRESENTATION AND SYMPTOMS 3.1 Respiratory Most intrathoracic goiters present in the elderly and appear frequently in the sixth decade. Thirty to forty percent are asymptomatic, and in about 20% of patients there is no palpable neck mass. The diagnosis is sometimes made by a routine chest x-ray disclosing a mediastinal mass. Reeve et al. (13) reviewed 967,759 screening radiographs in Sydney, Australia, and reported the incidence of substernal goiter to be 1 in 5040. Seventy to eighty percent of all patients, however, can be demonstrated to be sympto matic at the time of initial evaluation, most usually due to displacement and nar- rowing of the trachea (Fig. 1). Even though they may not be aware of a problem, dyspnea can often be provoked in approximately 85% of cases by raising both arms above the shoulders (Pemberton’s sign). Hoarseness is a rare symptom. The recurrent nerve may be paralyzed due to the long- standing compression or stretching of a benign goiter, but the presence of hoarseness and a paretic recurrent nerve raises a suspicion of thyroid malignan cy. Patients may be totally asymptomatic, but because of the bony confines of the thoracic inlet, the thyroid can act like an expanding mass within a rigid cage, leading to compression of vital structures. The most common symptom is related to compression of the upper airway. Ninety percent of symptomatic patients have mainly respiratory symptoms, including cough, hoarseness of voice, and shortness of breath. Symptoms range from mild to life threatening. Occasional dyspnea, cough, cya nosis, choking a ccompanied by suffoc ation, and respiratory collapse requiring emergency treatment may be seen. Shaha et al. (30) reported 24 patients with life-threatening respiratory symptoms, 9 of whom re- quired intubation. Patients with acute airway obstruction require intervention on an urgent basis and should remain on a ventilator until surgery because acute asphyxia may result if it is discontinued (14–16). 3.2 Esophageal Approxima tely one thir d of patients will experience difficulty in swallowing as a result of pressure on the esophagus as it is displaced posteriorly and laterally by the goiter. This can be confirmed by esophagram. It is not usually a major problem. 3.3 Vascular Obstruction Obstruction of venous return occurs in less 10% of cases. It may be minimal but can be demonstrated by elevating the patient’s arms (Pem berton’s sign) and observing the distention of neck veins. The symptoms and signs may become more severe as the intrathoracic mass becomes larger, progressing to a full-blown superior vena cava syndrome with dilatation of the veins of Figure 1 Schematic picture of mediastinal goiter with tracheal deviation. The bony confines of the thoracic inlet cause compression. Shaha134 the neck, face, and descending collateral venous circulation, as well as cyanosis. The appearance of symptoms of venous obstruction is an urgent indication for surgery. The obstruction may be due to the encroaching bulk of a benign nodular goiter or the result of malignant infiltrat ion. Compression of the mediastinal great vessels can produce obstructive symptoms. Other rare symptoms may be related to superior vena cava syndrome, downward esophageal varices, Horner’s syndrome, pleural effusion, and transient ischemic attacks secondary to the goiter stealing the blood from cerebral circulation (17–23). 3.4 Hyperthyroidism Multinodular goiters, whether they are in the neck or in the mediastinum, can develop autonomous hyper- functioning nodules, particularly if the goiter is long standing. Hyperthyroidism, as well as the presence of mediastinal goiter, is more common in elderly patients. Cougard reported an incidence of hyperthyroidism in 35% of 218 intrathoracic goiters in patients over 70 years if age. The cardiac effects of hyperthyroidism can be serious and often appear insidiously; arrhythmias, congestive failure, and ischemic heart disease carry a more serious impl ication in the elderly and may be life threatening. Radioactive iodine (RAI) has been used to control the hyperthyroidism of large multinodular goiters, but it often requires repeated doses and a long time period to be effective. Radiation thyroiditis following RAI is also a risk in patients with compromised airway and may precipitate acute airway obstruction. 3.5 Malignancy The incidence of overt cancer as well as incidental papillary carcinoma in mediastinal goiters ranges from 3 to 15% (14,15). If there is invasion of adjacent structures, a formidable surgical prob lem may result should laryngeal nerves or great vessels be involved. Lympho- mas and thymomas are the most common malignant tumors following intrinsic thyroid carcinoma. 4 DIAGNOSTIC PROCEDURES Many unsuspected intrathorac ic goiters are revealed by routine AP and lateral chest x-rays. This can indicate the extent of substernal mass and its location in the mediastinum. It may also disclose tracheal displacement and or compression, calcifications, soft tissue masses, or displacement of the pleural reflection. As noted previously, there may be no thyroid en- largement in the neck. But if a thyroid mass is present and the inferior margin cannot be defined, substernal extension is likely. Direct or fiberoptic laryngoscopy should be performed and may define laryngeal compression, distortion, or vocal cord paresis. However, airway compromise may be located well below the level of the larynx, requiring evaluation by imaging procedures. Computerized tomography offers additional important information that is of great value in the management of the substernal goiter (24,25). It outlines the continuity of the intrathoracic mass with the cervical thyroid. The addition of contrast material increases its value. The extent, location, and bor ders of the intrathoracic goiter can be precisely defined. The integrity of the airway, as well as the presence and sites of distortion or compression, can be accurately evaluated. Calcifica- tions and the homogeneity of the tumor can be easily assessed. By establishing the relationship of the goiter to the airway, esophagus, and great vessels, important information becomes available to the surgeon in deter- mining the operative approach. Magnetic resonance offers high-resolution imaging without the need for contrast agents. It offers a choice of tomographic cuts, and because of its greater accuracy in delineating soft tissue, it may more accurately delineate the goiter and adjacent structures such as trachea and vascular involv ement. Ultrasound, although of great help in the evaluation of cervical goiters, is not useful in substernal goiters because the bony thorax limits visibility. Barium swal- low may evaluate and locate the position of the esophagus and determine if there is any major compression. Thyroid scanning is rarely helpful and may often be misleading d ue to the nonfunctional portion of the substernal goiter. Thyroid function tests are generally within normal limits, although hyperthyroidism may accompany toxic nodules. Since most of the patients with substernal goiter are elderly, it is important not to assume that dyspnea is due solely to the goiter. Cardiac or pulmonary disease may account for part or even all of the symptoms. Pulmonary flow-loop studies can document the extent of pulmonary and extrapulmonary components of the dyspnea. 5 PATHOLOGY The majority of substernal goiters are benign multinodular goiters or follicular adenomas. Perhaps 10–15% are Mediastinal Goiter 135 malignant; papillary or follicular cancers and lymphomas predominate. Incidental papillary carcinomas are not unusual. Hyperplastic toxic nodules, lymphomas, and thyroiditis are also well recognized. Fifty percent of Hodgkin’s and 20% of non-Hodgkin’s lymphoma present as mediastinal masses. Due to the right-sided pre- dominance of paratracheal nodes, superior vena cava (SVC) syndrome is present in 20% of patients, particularly in those with non-Hodgkin’s lymphoma. Occa- sionally, anaplastic thyroid cancer may present as a substernal goiter; this condition produces rapid pro- gression of disease and severe symptoms. 6 SURGICAL APPROACH Most patients are symptomatic; the growth of the tumor is unpredictable. There is no satisfactory medical treatment for mediastinal goiter. The minimal regression seen with thyroid suppression offers no significant ben- efit, particularly if the mass is large. The majority of patients with substernal goiters should be considered for surgical intervention. The overwhelming number of substernal goiters, even though may extend deep into the thorax, can be removed through a neck incision because of their cervical blood supply. Only 1–3% require exploration through the chest wall. Most substernal goiters are localized to the right or left lobes; only 7–10% are found to be bilaterally. The majority of intrathoracic goiters are in the anteri or mediastinum. Perhaps 6–10% are found in the posterior mediastinum. A common location of goiters in the right mediastinum is between the superior vena cava and the vertebral bodies. Those on the left are more frequently anteriorly in the mediastinum, since the aorta acts as a posterior barrier. Kocher was the first surgeon to develop a techni que of surgery for substernal goiter and invented tools to facilitate its removal. He also described the technique of morcellation (piecemeal removal of the substernal goiter) in difficult cases. Lahey reported that nearly all the cases of substernal goiters could be easily removed through the neck (26–29). He stated: ‘‘It is a surprising fact that if the dissection is gentle and within the line of clearage, enormous masses may be removed into the neck with virtually no bleeding.’’ Lahey also popular- ized the technique of morcellation for removal of large substernal goiters, as well as the use of modified sternal splitting or widening using wedges in difficult cases. Although there is still some debate regarding partial or complete sternal split, a lateral thoracotomy may occasionally be necessary. There is a high likelihood of patients developing acute airway distress and compromise, and as patients get older the surgery may be more difficult. Shaha et al. (30) reported a 22% incidence of acute airway symptoms, with 8% of the patie nts requiring emergent intubation. 7 SURGICAL TECHNIQUE There are four main issues in the surgery for substernal goiter. 1. Retrieving the substernal portion of the thyroid in the neck 2. Avoiding major bleeding from inferior thyroid veins 3. Preserving the parathyroid glands 4. Careful identification and preservation of the recurrent laryngeal nerve A variety of methods and technical details are described in the literature (31–33). The standard technique is as follows: a generous skin incision should be used. This is carried through the platysma and flaps are raised in the plane beneath this muscle. The dissection is continued in the midline. Generally the strap muscles are divide d. At the minimum, the strap muscles should be transected on the side of a large substernal goiter. The middle thyroid vein is divided, ligated, and the superior thyroid vessels are divided and ligated close to the thyroid parenchyma. The identification of the recurrent laryngeal nerve may be quite difficult due to the large size of the substernal goiter and the displacement of the nerve. As the strap muscles are divided, they should be retracted away from the thyroid. A careful attempt is made to stay on the thyroi d capsule and to be aware of the possibility that the recurrent nerve may be stretched over the thyroid mass in an unusual manner. Multiple inferior thyroid veins should be clamped and ligated carefully. Hemoclips may be helpful in this region. Special attention should be given to the identification and preservation of the superior parathyroid glands since the lower glands are more vulnerable to injury or devascularization as the goiter is delivered and removed from its substernal location. Gentle blunt dissection is helpful in the substernal area under the strap muscles; it is best approached starting laterally from the under aspect of the sternomastoid muscle and extending medially (Fig. 2). Occasionally the medial head of the sternomastoid may require transection for better exposure. Injury to the inferior thyroid veins can produce serious bleeding; retraction of these veins into the mediastinum or the tearing of veins Shaha136 below the level of the sternum can become a critical problem, sometimes requiring a sternotomy for control of the bleeding. As the finger dissection is continued from the lateral surface and after ligation of multiple small inferior veins, the thyroid is generally delivered into the neck. At the beginning of the operation it is impor tant to determine whether the goiter is in the posterior mediastinum with displacement and stretching of the recurrent laryngeal nerve anteriorly over the mass. If the thyroid mass is shelled out in this situation, the risk is that the overlying nerve will be avulsed with the speci- men. It is advisable, whether the goiter is in the anterior or posterior mediastinum, to trace the course of the nerve, if possible, before removal of the substernal mass, protecting it from injury. If there is difficulty in finding the recurrent nerve inferiorly, a good alternative is to identify the nerve as it enters the trachea under the cricothyroid muscle at the junction of its middle and anterior third and then follow it downward. At times, however, identification and tracing of the recurrent laryngeal nerve may be difficult or impossible without delivering the substernal thyroid mass from the mediastinum and then dissecting laterally to find the nerve and the parathyroids. The dissecting hand is turned so that the palmar surface faces the sternum and blunt dissection is used to gently deliver the thyroid mass. A variety of techniques have been described to find the recurrent laryng eal nerve and to carefully preserve it. The nerve may be considerably displaced in substernal goiter. It may be intimately adherent to the posterior capsule of the thyroid, displaced medially (along with displacement of the trachea and esophagus), or in very rare instances it may be displaced anteriorly— especially if the substernal goiter or a portion of it originates and extends into the posterior mediastinum. After taking down the superior thyroid pole and middle thyroid vein, the dissection proceeds on the posterior- medial surface of the goiter with careful identification of the inferior thyroid artery and recurrent laryngeal nerve. Sometimes, because of the large size of the thyroid, this may be impossible. Under these circum- stances, it is more appropriate and easier to retrieve the thyroid from the substernal area and look for the recurrent larynge al nerve in the tracheo-esophageal groove. It is extremely important to remain as close to the thyroid capsule as possible to avo id injury to the nerve, which may be intimately adherent to the posterior capsule of the thyroid. Once the thyroid is retrieved from the substernal portion, the recurrent laryngeal nerve can be easily identified majority of the time in the tracheo-esophageal groove, anterior to the inferior thyroid artery. The nerve may be located behind the inferior thyroid artery. Charles Proye from Lille, France, has described a ‘‘toboggan technique,’’ which is essentially finding the recurrent laryngeal nerve at the cricothyroid area and resecting on its surface, pushing the thyroid anteriorly. Once the nerve is found in the cricothyroid area, the remaining surgery becomes quite simple. The dissection is performed on the surface of the nerve, pushing the thyroid anteri orly and medially. In the author’s judgment, this technique may be difficult, especially if there is a bulky thyroid substance in the cricothyroid area. However, one may sometimes use this technique profitably even when the goiter is quite large. After taking down the superior thyroid pole, the cricothyroid Figure 2 The technique of surgery for mediastinal goiter. Careful ligation of the inferior thyroid veins is necessary to avoid unexpected bleeding. Injury to the recurrent laryngeal nerve may be avoided by being aware of its location. The substernal goiter is retrieved by finger dissection. 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After Surgery Serum calcitonin (ng/L) Month/year 2/86 2/86 10/86 5/87 4/88 5/89 9/90 11/91 3/ 92 Basal Peak CEA (Ag/L)c 17,000a 30 0a 440a 470a 840a 860a 31 b 64b 35 6b 19,000a 290a 420a 400a 800a 880a 52b 146b 732 b 6 5 5 .3 5.5 12 25 85 240 bution of calcitonin-poor C cells To our surprise, the postoperative calcitonin test was normal and at later check-ups the CEA value was normalized CEA has a long half-life;... 50%) of calcitonin-immunoreactive cells, Table 3 Importance of MTC Type to Postoperative Survival Authors (Ref.) Treatment period Type of MTC Saad et al (7) 1944– 83 Raue et al (54) 1967–91 Sporadic Familial Sporadic Familial a Five patients with MEN-2B syndromes excluded No of patients 125 30 559 182 (81%) (19%)a (75%) (25%) Age (yr) at presentation 5- and 10-year survival (%) 46 32 50 33 74 and 55 100... 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