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Thyroid Factor

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Many patients with differentiated thyroid cancer have metastatic spread within the regional lymph nodes and for the majority, this usually represents occult disease [1-4]. Its frequency is related to histology (more common in papillary thyroid cancer) and to the size of the primary tumor. The chances of having regional lymph node metastases with follicular carcinoma is much lower and occurs in less than 20% of cases [2].

Lymph node metastases in differentiated thyroid cancer are often multiple, and of variable size and this is one of the arguments for selective neck dissection of "at risk levels" rather than "berry picking" (selective removal of isolated lymph nodes) [20,25].The latter procedure has now been shown to have a less favorable prognosis than formal neck dissection [28]. The spread of disease is usually ipsilateral [20,25], and involves progression in an orderly defined manner from level VI either laterally to levels III and IV or inferiorly into the mediastinum (level VII). Spread into level II either occurs from the superior pole of the thyroid or directly from levels III and IV. Spread into level I and the retropharyngeal and parapharyngeal spaces tends to occur when other levels are involved, or in the previously treated neck.

Many studies show that lymph node involvement is associated with a significantly higher risk of both local and regional recurrences and of distant metastases [1]. It is not clear whether its presence has an impact on survival because other prognostic factors are involved. There does appear to be an increased risk of cancer-related mortality when lymph node metastases are extensive, bilateral, located in the mediastinum, associated with extensive primary disease, or when they occur in elderly patients [1].

In the past, there has been a trend not to perform elective lateral neck dissection in patients with differentiated thyroid cancer but to perform a "berry picking" procedure for palpable disease. There is now strong evidence to support a formal selective neck/modified radical neck dissection (dissecting at least levels III, IV, and VB) in the lateral compartment for palpable or suspected disease [20,25,28]. This is on the basis of the high incidence of nodal involvement, and that formal lymph node dissection facilitates accurate workup of the initial extent of the disease. Furthermore, a number of studies have shown improved outcomes with formal lymph node dissection [25] and in one series, the 20-year recurrence rate was significantly reduced after formal lymph node dissection [29]. In one study, recurrent disease after lymph node spread from papillary thyroid cancer was associated with a significant increase in the risk of death [30]. Surgery is the most effective way of treating lymph node metastases, and in particular those nodes in the so-called "coffin corners" where detection is difficult such as the retropharyngeal and parapharyngeal spaces, pre- and paratracheal grooves, and Chais-saignac's triangle (Figure 13.4).

The majority of patients have a palpable goiter and are clinically N0 in both level VI and

Figure 13.4 The relationship of the prevertebral fascia to the scalene muscles and the structures over the apex of the left lung (Chaissaignac's triangle). (Reproduced from Last RJ, Anatomy Regional and Applied, 6th edn, London: Churchill Livingstone, 1978, page 377.)

Table 13.6 Lymph node staging according to the 6th edition of the UICC-AJCC TNM classification [27]

N

Regional nodes

NX

Regional lymph nodes cannot be assessed

NO

No regional lymph node metastasis

N1

Regional lymph node metastasis

N1a

Metastasis in level VI (pretracheal and

paratracheal, including prelaryngeal and

Delphin lymph nodes)

N1b

Metastasis in other unilateral, bilateral, or

contralateral cervical or upper/superior

mediastinal lymph nodes

INFERIOR THYROID ARTERY

VERTEBRAL ARTERY

SCALENUS ANTERIOR

PHRENIC NERVE

INFERIOR THYROID ARTERY

SCALENUS ANTERIOR

PHRENIC NERVE

VERTEBRAL ARTERY

Figure 13.4 The relationship of the prevertebral fascia to the scalene muscles and the structures over the apex of the left lung (Chaissaignac's triangle). (Reproduced from Last RJ, Anatomy Regional and Applied, 6th edn, London: Churchill Livingstone, 1978, page 377.)

PHRENIC

ANSA NERVE

SUBCLAVIA

THORACIC DUCT

SUBCLAVIAN VEIN

THE RELATIONSHIP OF THE PREVERTEBRAL FASCIA TO THE SCALENE MUSCLES AND THE STRUCTURES OVER THE APEX OF THE LEFT LUNG.

the lateral neck compartment (levels II-V). Some workers now argue strongly that at the time of initial thyroidectomy, level VI should be routinely dissected [25,31,32], particularly for high risk disease, although its exact role awaits clarification [33]. Its use is justified on the basis that recurrence and reoperation rates may be reduced and overall survival improved although there is no prospective evidence to support this. Indeed, some surgeons extend the dissection to the ipsilateral supraclavicular area, thereby allowing elective dissection of the retrovascular and external part of the jugulocarotid chain, as well as the transverse superficial chain along the accessory nerve in level V [25]. This dissection is performed through a transverse incision and the operative specimen submitted to frozen section. Morbidity is said to be low [25] but the same authors acknowledge that level VI dissection increases the risk of hypoparathy-roidism and recurrent laryngeal nerve palsy [25]. Although there are no prospective studies looking at whether there is any increase in complication rates following elective lymphadenec-tomy of the central compartment, one study showed that the rates of temporary and permanent hypoparathyroidism following level VII dissection were 70% and 50%, respectively [34]. In a personal series of 363 total thyroidectomies from 1993 to 2003 (of whom 147 had a routine level VI neck dissection for differentiated thyroid cancer), the incidence of temporary and permanent hypoparathyroidism was 19% and 1.9%, respectively. In those patients having lobectomy or total thyroidectomy for malignancy (n = 353), the incidence of temporary and permanent recurrent laryngeal nerve palsy was 1.4% and 0.9%, respectively. The wound infection rate was 0.9% and hematoma rate 1.4%.

Patients with differentiated thyroid cancer (particularly papillary) are at high risk of occult cervical metastases. The central compartment (level VI) can be evaluated by both palpation and elective imaging, and high risk patients considered for elective neck dissection. Another alternative would be to consider sentinel node biopsy. This involves intraoperative surgical mapping of the first echelon lymph nodes using an injection of 1% isosulfan blue dye into the thyroid nodule. Within seconds, the dye can be seen to pass to the sentinel lymph node. One study looked at 12 malignant cases (11 papillary, 1 follicular), all of whom had an N0 central com partment. Of these, only 5 out of 12 had positive sentinel nodes and there was one false-negative and one false-positive result. The problem is this technique involves injecting the nodule and violates an oncologically significant area (level VI). It may also highlight the parathyroids, sometimes leading to their inadvertent removal. Further studies are awaited but currently elective neck dissection in high risk patients is probably safer and more cost-effective than sentinel node biopsy, and proceed to central neck dissection if the node is positive [35].

How then should we manage our patients? Several different types of lymph node dissection may be done in patients with differentiated thyroid carcinoma (Table 13.7). For those undergoing a unilateral lobectomy for a suspicious fine-needle aspiration cytology (FNAC) for a papillary carcinoma, a unilateral level VI neck dissection may be performed in high risk patients (those with T3/T4 tumors, children, males >45 years) which removes the soft tissue and lymph nodes in that area with preservation of both recurrent laryngeal nerves, the external branches of the superior laryngeal nerves and all the parathyroid glands (Table 13.7). For a suspected or proven malignancy when a near-total or total thyroidectomy is being performed, this procedure is carried out bilaterally. Large nodules in the isthmus (T3/T4 lesions) require

Table 13.7 Neck dissections performed for differentiated thyroid carcinoma

• Level VI neck dissection

• Level VII neck dissection

• Selective neck dissection (usually levels IIA to Vb or levels III and IV, levels III to Vb, or levels IV to Vb)

• Modified radical neck dissection (type 1) preserving the accessory nerve (levels I-V dissected)

• Modified radical neck dissection (type 2) preserving the accessory nerve and the internal jugular vein (levels I-V dissected)

• Modified radical neck dissection (type 3) preserving the accessory nerve, internal jugular vein, and sternomastoid muscle (levels I-V dissected). Sometimes called a comprehensive neck dissection.

• Radical neck dissection (levels I-V dissected).The accessory nerve, internal jugular vein, and sternomastoid muscle are all sacrificed.

• Extended radical neck dissection (levels I-V dissected).This involves a radical neck dissection with sacrifice of other structures such as external skin, digastric muscle, etc.

bilateral dissection. At the time of surgery for near-total or total thyroidectomy, levels II, III, and IV should be palpated. If there is any suggestion of metastatic spread, a frozen section should be performed and the presence of metastatic disease indicates the need for an elective selective dissection of the lateral neck compartment. There is confusion in the literature about which levels should be routinely dissected. One study has shown that in the presence of palpable disease, nodal involvement is at a single level in 39% of cases, while 14% of cases involved four or more levels [36]. The majority of surgeons will always dissect at least levels III and IV [31,36; Professor J. Shah, personal communication; Professor C. O'Brien,personal communication] and some also routinely dissect levels IIA to VB (Professor P. Gullane, personal communication). In the presence of gross disease in level IIA, level IIB should be dissected as recurrent disease at this site is difficult to treat surgically (Professor J. Shah,personal communication). The author's preference for palpable neck disease is to dissect at least levels IIA to VB (below the accessory nerve) with preservation of the sternomastoid muscle, internal jugular vein, and the accessory nerve [37]. This falls just short of a modified radical neck dissection type three (comprehensive neck dissection) since level I is not usually routinely dissected, although in one series, approximately 12% of cases had disease at this level [20]. This procedure may be extended to include level I, and then one or other of the accessory nerve, internal jugular vein, or sternomastoid muscle may need to be sacrificed for more advanced disease (modified or radical neck dissection). This is discussed below. Palpable disease in level VI is treated with a level VI neck dissection.

Treatment of lymph node metastases for fol-licular carcinoma is treated in a similar way to the papillary cancer, although there seems little justification to perform a level VI neck dissection in the N0 neck as the chance of occult disease is less than 20%.

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