RSS

Pharynx & Larynx-3

EVALUATION OF THE THYROID NODULE

Background

Management of the thyroid nodule remains a challenge for the physician. Mazzaferri writes, “The trouble with thyroid nodules is that there are too many of them, and they tend to cause terrible apprehension because their behavior is so unpredictable. Thyroid nodules comprise a gamut of disorders with widely differing biologic behaviors, ranging from benign tumors with no malignant potential to aggressive thyroid cancers that may kill within a matter of months. Add to this the fact that concealed among the millions of nodules are only a relatively few thyroid cancers, most of which are completely curable, and one has woven the fabric of a serious diagnostic dilemma.” 18 The otolaryngologist / head and neck surgeon encounters thyroid nodules commonly in practice, and an understanding of the diagnostic workup options is important.

Epidemiology

One of the most widely cited epidemiologic studies involves the population study of Framingham, Massachusetts. In this study palpable thyroid nodules were found, in adults between 30 and 59 years of age, in 6.4 % of women and 1.5 % of men. Additionally, the nodule accrual rate was found to be 1.3% at 15 years, or an annual accrual rate of 0.09%33. However, the prevalence is much higher when assessed by autopsy, palpation at surgery, or by ultrasound. Mazzaferri pooled a number of studies and found that the prevalence of nodules by these methods is approximately ten times that of the prevalence by physical exam17. One autopsy study noted nodules in 65% of men and 80% of women in the ninth decade. Looking at numerous studies, one can draw a number of conclusions. First of all, thyroid nodules are more common in women. Also, the prevalence of thyroid nodules increases with increasing age. Physical exam alone is far less sensitive than other methods of detecting thyroid nodules, but the importance of nodules found by other methods has generally yet to be determined.

Thyroid cancer occurs at an incidence of approximately 12,000 cases per year with about 1,000 deaths per year. When one looks at autopsy series, however, the incidence of thyroid cancer can be as high as 35%. Currently there is no reliable way to distinguish a prioi an aggressive thyroid cancer from an indolent one.

Histologically, thyroid cancer occurs as a number of different types. Papillary is the most common, accounting for around 70% of thyroid cancers. Follicular accounts for around 15%, medullary another 5-10%, and anaplastic another 5%. Additionally lymphoma may arise in the thyroid, especially in a setting of Hashimoto’s thyroiditis. Metastasis to the thyroid may occur, usually from breast, lung, kidney, gastrointestinal sources, or from melanoma.

Pregnancy

 

 

One special circumstance that deserves comment is the thyroid nodule in the pregnant patient. Studies have shown that parity increases the incidence of thyroid nodules- in one study (using ultrasound) from 9.4% of nulliparous women to 25% of parous women31. Additionally, other investigators have cited the higher incidence of thyroid carcinoma in pregnant patients in whom a carcinoma arises 19,26. Some have reported increased biologic aggression of thyroid cancers in pregnant women. Other authors disagree and feel that pregnancy effects no changes on the pathophysiology of thyroid disease.28 It has been suggested that human chorionic gonadotropin (HCG) may have thyroid-stimulating hormone (TSH) -like activity, acting as a growth promoter. Workup should include a fine-needle aspiration biopsy (FNAB), and perhaps an ultrasound, but radioactive scanning is contraindicated. Some have recommended surgery either before or after, but not during, the third trimester. Should I-131 ablation be needed postoperatively, the mother should avoid breast-feeding during this time. Also, given the potential exacerbating effects of pregnancy on thyroid cancer, some authors advocate avoidance of pregnancy in a woman who has had a thyroid cancer. 3

Radiation

Ionizing radiation remains the only unequivocal environmental cause of thyroid cancer. Between the 1920’s and the 1950’s, an estimated one million Americans received head and neck irradiation for benign disease. Duffy, in 1950, recognized the association of childhood irradiation and thyroid cancer in a young man with thyroid cancer who had had thymic irradiation as an infant.32 This was borne out in other studies, as was the increased incidence of thyroid nodules and thyroid cancer in people exposed to radiation for other reasons. Some dramatic examples include Marshall Islanders accidentally exposed to nuclear fallout and Japanese persons exposed to irradiation from the atomic bombs at Hiroshima and Nagasaki.6,27 Persons receiving external irradiation therapeutically (e.g. for cancer) are also at increased risk. Some have found slightly increased risk in certain occupational exposures, such as X-ray technicians. Others have suggested background terrestrial sources or increased celestial sources at altitude as risk factors, but this association has not been demonstrated.26

Children

Children represent a distinct population of thyroid nodules. As noted earlier, irradiation was commonly given in years past for benign conditions. In 1976, the National Institutes of Health (NIH) began a widespread effort to urge notification and examination of individuals exposed to irradiation as children. Some of these individuals and their parents were not aware of the exposure. Some hospitals routinely irradiated the thymus of all infants to prevent crib death. Other conditions treated with radiation include adenotonsillar hypertrophy, acne, eustachian tube dysfunction, bronchitis, hemangiomas, and tinea capitis.

Given this background, it is notable that in the 1950’s approximately 70% of thyroid nodules in children represented cancer, whereas currently that number is closer to 20%. Ten percent of all thyroid cancer occurs before age 21, and thyroid cancer represents 1.5-2% of all pediatric malignancies.

Special mention should be made of medullary thyroid carcinoma (MTC). This neoplasm has been shown to have germ-line transmission, either alone (familial MTC), or as part of the multiple endocrine neoplasia type 2 syndromes (MEN2A and MEN 2B). Previously screened for with calcitonin levels following calcium-pentagastrin stimulation, this has been replaced with DNA screening for the RET proto-oncogene found on chromosome 10. Children with a family history positive for MTC who test positive for RET are recommended to undergo a prophylactic thyroidectomy in the first few years of life.

History & Physical

History

As with every clinical encounter, all new thyroid nodule patients begin with a history and physical. Beyond the usual questions, certain questions specific to the history of the thyroid patient should be included. Age less than 20 or greater than 60 has been suggested as having a higher incidence of cancer in a thyroid nodule. Gender is important- a nodule in a man is more likely to be cancer (although cancer overall is more common in women). Exposure to radiation is an important history item. Symptoms referable to hyper- or hypo- thyroidism should be elicited. Rapid enlargement of a mass is generally considered a poor sign unless there is associated pain which may indicate hemorrhage into a nodule.

Special history questions include history of Gardner’s or Cowden’s syndromes ,as these have been linked to a higher incidence of thyroid carcinoma. As discussed previously, family history of medullary thyroid carcinoma is important to know in a child. Additionally, some have suggested family history of other types of thyroid cancer to be a soft risk factor. Hashimoto’s thyroiditis can predispose a person to lymphoma, so this should be entertained during the history.

Although no element of the history is terribly sensitive or specific for thyroid carcinoma, certain history items may suggest invasion of local structures which, in turn, suggest malignancy. These include dyspnea, hoarseness, and dysphagia. Progressive enlargement and/or other high-risk factors should alert the clinician to the possibility of carcinoma.

Physical

As always, a complete head and neck examination in is order. The thyroid is best examined from behind. Both lobes and the isthmus should be palpated, and the patient should swallow to confirm that any masses are in the thyroid.4 Any nodules should be noted, as well as diffuse changes. With respect to the possibility of thyroid cancer, certain things should be emphasized. Vocal cord motion should be checked, and some advocate the use of preoperative videostrobolaryngoscopy to look for subtle abnormalities and for documentation. At our institution, this is not commonly done. It should be noted that the literature indicates that a fair number of benign masses may present with vocal cord paresis. The presence or absence of adenopathy should be noted. Lastly, in a patient with symptoms of hyperthyroidism, the eyes should be checked for exophthalmos and scleral show. Although physical examination is not very sensitive or specific for detecting thyroid cancer, certain findings such as fixation of a mass, induration, vocal cord fixation, adenopathy and stridor should raise the clinician’s level of suspicion.

A classic study was done by Hamming et al compared physical examination finding to cytological findings obtained by fine-needle aspiration biopsy, ultimately with histological confirmation. In patients who were felt by clinical grounds to have a high suspicion of malignancy there was a 71% prevalence of malignancy. Criteria for high clinical suspicion included rapid growth of tumor, vocal cord fixation, very firm nodule, fixation to adjacent structures, enlarged regional lymph nodes, and distant metastasis. A small subset of patients had two of these findings, and all had malignancy. Patients were stratified to a moderate clinical suspicion if they were younger than 20 or older than 60, had a history of head and neck irradiation, were male with a solitary nodule, had dubious fixation, or had a lesion over four centimeters which was partially cystic. In this group the prevalence of malignancy was 14%. All other patients were considered to have a low clinical suspicion of malignancy, although 11% were ultimately found to have a malignancy.

Workup & Management

After the history and physical, the clinician has a number of tools at his or her disposal for investigating the nature of the nodule. These include serum testing, needle biopsy, and imaging. The precise management of the workup of the thyroid nodule is controversial, balancing individual bias, the clinical picture, patient expectations, clinical availability, and cost-effectiveness. A thorough understanding of the options will allow the clinician to make appropriate decisions in a given clinical encounter.

Serum Testing

Many advocate serum testing of thyroid function as an initial step (although many advocate fine-needle aspiration biopsy as an initial step, others feel that the subgroup of patients who have a hyperfunctional nodule as evidenced by lab and nuclear studies can be safely observed). The single-most important test is an assay of thyrotropin, or thyroid-stimulating hormone (TSH). This alerts the clinician to one of three states: hyperthyroid, euthyroid, or hypothyroid. Even if a patient is asymptomatic and has a normal level of thyroxine (as assayed by the free T4 or free thyroxine index), a “normal” level of thyroxine in the face of an abnormal TSH in inappropriate. For example, a T4 level within the laboratory range of normal in the face of an elevated TSH indicates subclinical hypothyroidism, as an elevated TSH ought to produce an elevated T4 level, which under normal conditions would feedback and lower the TSH to an appropriate level.

Other serum tests are not generally ordered will be briefly mentioned. In medullary thyroid carcinoma, many would consider calcitonin levels, as well as regular electrolyte tests. Additionally, the RET proto-oncogene remains the test of choice for MTC. If one suspects Hashimoto’s thyroiditis, anti-thyroid antibodies can be assayed. Thyroglobulin is a useful assay in the postoperative care of the thyroid cancer patient, as a rising level likely indicates recurrence.

FNAB

Fine-needle aspiration biopsy (FNAB or FNA) is almost universally accepted now as the single most important test in the evaluation of a thyroid nodule. Initially described in the 1920’s, it was reintroduced in 1952 by Söderström which led to its use in Scandinavia and then the rest of Europe.2,14 It was not until the 1970’s, though, that this technique caught on in America. Previous concerns about seeding of malignancy along the needle track have not been borne out clinically, and lower rate of complications, as well as the ease and simplicity, make it a more attractive option than larger bore needle biopsies. Some have also used this technique for the introduction of a sclerosing agent as a therapeutic option for certain thyroid nodules.

Briefly, although techniques vary, somewhere between a 21 and 27 gauge needle is placed within the lesion. Initially aspiration should be attempted, as a purely fluid-filled cyst may be “cured” by this technique. Next, either with or without suction applied, the needle is passed back and forth over a small range until material is collected in the hub. After withdrawal of the needle, the needle is briefly detached to allow air introduction into the syringe (air introduction before the procedure may weaken the suction), and the collected material expelled onto a slide which is then smeared and fixed for cytology. Very small or very large lesions may introduce sampling error, and the accuracy of FNAB is improved by multiple passes. Excessive blood reduces the ability to interpret the material. Skill and experience of the cytopathologist also play a role in the usefulness of the data.

Campbell and Pillsbury evaluated the results of nine different studies in which 912 patients who received FNAB ultimately underwent surgery. They found a range of false-negatives from 0.5% to 11.8% with a pooled rate of 2.4%. As for false-positives, the range was between 0% and 7.1 % with a pooled rate of 1.2%. this translated to an overall accuracy of over 95%, a result which correlates with other published data.

Results from FNAB can be categorized as benign, malignant, insufficient/inadequate, and indeterminate/suspicious. The latter occurs in certain situations, a common example being that of follicular neoplasm. The differentiation between follicular adenoma and carcinoma is made by evidence of capsular invasion, a finding that has to be made histologically. Largely cystic aspirations are often hypocellular and result in a “insufficient” diagnosis. Many recommend re-aspiration of these cysts (if they are not gone), and if a second aspiration is inadequate then progressing to surgery.

Imaging — Nuclear Medicine

The thyroid scan was a mainstay in the evaluation of the thyroid nodule prior to the widespread use of FNAB. The concept is based on the observation in 1939 that malignant thyroid tissue only uptakes a small amount of iodine as compared to normal thyroid tissue.2 This property was exploited by administering a radioactive iodine tracer and then using the radiation to image the thyroid gland. Nodules could be classified by their uptake of tracer as “hot”, “warm”, and “cold”. It was thought that cold nodules were more likely to be cancerous. Although true, the sensitivity and specificity of this technique has relegated it to second-tier status behind FNAB.

A brief discussion of the tracers is in order. The two most common tracers are iodine and technetium. These are used to image papillary and follicular carcinoma. Iodine occurs in a number of isotopes, with 127I being the common stable form. 125I had a role in the past, but is no longer used. The two commonly-used isotopes are 123I and 131I. 123I is manufactured in a cyclotron and has a half-life of 13.3 hours. Its gamma radiation has optimal imaging characteristics, but it is expensive and difficult to obtain, and it does not have a long shelf life. 131I, on the other hand, is a product of nuclear fission and has a half-life of 8.1 days. It is cheap and easily obtained. It has both beta and gamma emissions, and this coupled with its longer half-life mean a larger radiation exposure to the patient. Also its gamma emissions make for suboptimal pictures compared to 123I. On the other hand, this isotope is the preferred agent for radioiodine ablation of residual or metastatic thyroid carcinoma.

99mTechnetium is a product of beta decay of 99Molybdenum. The “m” refers to a metastable state that has a relatively long half-life. Thus, the 99mTc exists at a higher energy state until it undergoes isomeric gamma decay to 99Tc. Its half-life is six hours, and it is readily available. Its characteristics are such that images can be obtained shortly after administration. This has made it popular for thyroid clinics in which the patient can go get imaged and return to clinic. The technetium is trapped by the thyroid but not organified (processed into hormone) as iodine is. Thus, a “hot” technetium nodule is not the same as a hyperfunctional thyroid nodule (a distinction of which to be aware when reading the literature). Therefore, any hot nodule on technetium scanning should undergo confirmation by iodine scanning. Occasionally there is a discrepancy, and this is referred to as a discordant nodule. A discordant nodule has a higher cancer risk than a cold nodule, and should be managed with appropriate vigilance.

Other isotopes are sometimes used. Thallium has the advantage that one does not have to be off of thyroid hormone to undergo testing. However, its sensitivity and specificity are suboptimal, and it is expensive. It may have a role in detecting metastasis in non-iodine avid tumors (ones with poor iodine sensitivity) or in patients with a large reservoir of iodine in their body (e.g. after contrasted CT). Additionally, it sometimes will concentrate in medullary carcinoma which can then be imaged. 67Gallium is usually used as a non-specific marker for inflammation, but in thyroid scanning it is occasionally used to image anaplastic carcinoma or lymphoma. 99mTc-Sestamibi concentrates in the mitochondria and is usually used for cardiac imaging. Hürthle cell neoplasms, which are rich in mitochondria, are poorly imaged with conventional techniques but are imaged well with sestamibi. Other agents are infrequently used, either in special or investigational circumstances.

The utility of thyroid scanning is currently limited. A review of 4457 patients with thyroid nodules who underwent imaging and surgery revealed that the prevalence of cold, warm, and hot nodules was 84, 10, and 5.5% respectively. Of the cold nodules, 16% were malignant. Of the warm nodules, 10% were malignant. Of the hot nodules, 4% were malignant.2 This data did not note the thyroid status of the patients. Many authors currently recommend thyroid scans for hyperthyroid patients (by TSH testing) with the belief that the prevalence of cancer in hot nodules is low in these patients who may be safely followed. Also, some authors recommend scanning nodules which are indeterminate by FNAB and following clinically the hot nodules. Whatever the indication, almost all authors recommend further workup for cold or warm nodules. One final clinical note — a hyperthyroid patient with a nodule (if his or her physician follows hot nodules clinically) should still undergo a scan, as cold nodules may arise against a background of diffuse thyroid hyperfunction.

Imaging — Ultrasound

Ultrasound has emerged as a diverse modality which has utility in the management of thyroid disease. Perhaps its most widely used role is that of localization for FNAB. This occurs when there is a small nodule that is difficult to reliably sample, or in the case of the non-palpable nodule. The non-palpable nodule by definition has been located through some other technique. Since ultrasound has a lower limit of resolution of 2-3mm, determining the management of incidentally-located non-palpable nodules is controversial, given the high prevalence of nodules. One author recommends ultrasound-guided FNAB for patients with a family history of thyroid cancer, a history of radiation exposure, a nodule greater than 1.0cm, or a nodule with suspicious ultrasonographic features. Absent these, he recommends serial ultrasonography.34 Suspicious ultrasonographic features include presence of a halo, irregular border, presence of cystic components, presence of calcifications, heterogenous echo pattern, or extrathyroidal extension. No findings are definitive but these should be weighed in the whole clinical picture.

Ultrasound may also be used to serially follow a lesion (i.e. after suppression). It is useful for determining cystic versus solid, and in children with hypothyroidism or with a thyroglossal duct cyst it is a good screen for the presence of normal thyroid. Also, pregnant women cannot undergo radioactive imaging, and ultrasound may play a lager role in their management. Although it can aid in the distinction of a solitary nodule from a multinodular goiter, this distinction is somewhat academic as most now feel that the risks of a dominant nodule in a multinodular goiter are the same as the risks of a solitary nodule.

Imaging — Other

Other modalities have a limited role in thyroid disease. Plain films may incidentally show tracheal deviation. Calcifications on plain films are sometimes associated with thyroid carcinoma, but this is neither sensitive or specific. Computed tomography (CT) and magnetic resonance imaging (MRI) may play adjunctive roles, especially if there is bulky regional neck metastasis. One should keep in mind that the contrast agent for CT scanning is iodinated and may adversely affect the postoperative ability to treat with 131I. Non-contrasted CT may be better, if feasible. Positron emission tomography (PET) scanning is not widely available and is still largely investigational.

Thyroid Suppression

Thyroid suppression has been utilized in the past in the management of thyroid modules. This practice is based on the idea that benign nodules would be TSH-responsive whereas malignant nodules would not. Dropping the TSH with exogenous thyroxine would shrink benign nodules but not malignant ones. Unfortunately, this theory does not translate into reality very well. Five placebo-controlled trials of suppression for benign nodules suggest (although not conclusively) that there is no shrinkage with treatment.13 Even if there is, some nodules later shown to be malignant have been shown to shrink with suppression. Additionally, suppression carries with it the risk of increased osteoporosis, although this has not been shown to clinically translate into increased fractures. Although a short trial of suppression may be reasonable in selected cases,13,28 many authors do not see a role for suppression in the management of nodular thyroid disease. 9,14,17 A notable exception is individuals who received childhood irradiation to the head and neck, as suppression has been shown to decrease the incidence of nodules dramatically.10

Management

Ultimately, then the management of a thyroid nodule should include a history and physical, followed by further testing. Most patients will need an FNAB and a TSH. Benign nodules(by FNA) should be followed and re-aspirated if they do not regress.28 A benign nodule in a hyperthyroid patient may be considered for scan, and if the scan is hot considered for clinical follow-up, otherwise more testing (repeat FNA versus surgery). Inadequate aspirations should be re-aspirated, and if still inadequate should be considered for surgery. Indeterminate aspirations, although scanned by some, are usually considered for surgery in our institution (one problem in making a uniform algorithm being that indeterminate and suspicious are in the same category — clinical management may depend on discussion with the cytopathologist as to the specific findings). Constant vigilance is key to optimum outcomes, and a thorough understanding of the ideas behind algorithmic approaches permit flexibility when the patient does not fit nicely into the algorithm. For example, one author who writes extensively on this topic recommends serious consideration of surgery for any male over 60, regardless of the FNAB, due to the high pretest probability of malignancy.18 This recommendation, although itself a generalization, is based not in a “one-size-fits-all” approach to management but based upon a thorough understanding of the scientific basis behind the management of a thyroid nodule that the individual clinician can apply to individual patients for optimum patient care.

 

BENIGN THYROID DISEASE 

Introduction

Knowledge of benign thyroid disease is important for the otolaryngologist head and neck surgeon as thyroid surgery accounts for a major portion of all operations performed in the head and neck region. Although most of these surgeries are indicated to treat malignant or potentially malignant tumors, surgical indications exist for treatment of many benign diseases of the thyroid. Benign diseases of the thyroid are quite common and affect women more frequently than men by a ratio of 5 to 1. The prevalence of thyroid nodules determined by ultrasound or autopsy is 30 to 50 percent; only five percent of these are malignant. Benign thyroid disease will be evaluated by the head and neck surgeon for a variety of reasons including: compressive symptoms, differentiation from malignant disease, cosmetic deformity, and failure of medical management of thyroid disease. Benign thyroid disease can be divided into benign nontoxic, benign toxic and inflammatory conditions. This paper will review nontoxic diffuse and nodular goiter, toxic multinodular goiter, thyroid adenoma, toxic diffuse goiter (Graves’ disease), chronic thyroiditis (Hashimoto’s), subacute thyroiditis (De Quervain’s), and Riedel’s thyroiditis.

Anatomy and Physiology

The thyroid gland is composed of 2 encapsulated lobes, one on either side of the trachea, connected by a thin isthmus that crosses the trachea anteriorly just below the cricoid cartilage. Occasionally, a pyramidal lobe is found extending superiorly from the isthmus in the midline. Embryologically, the thyroid develops as a thickening in the pharyngeal floor that elongates inferiorly as the thyroglossal duct and divides into 2 lobes as it descends through the neck. Congenital thyroid anomalies include: failure of one or both thyroid lobes to develop (agenesis or hemiagenesis), thyroid remaining at the base of tongue (lingual thyroid), thyroid tissue found at other locations between the base of tongue and lower neck (thyroglossal duct remnant), and substernal thyroid. In the case of a substernal thyroid, the thyroid follows the developmental path of the heart into the thorax where it may later manifest as a substernal goiter with compression of the trachea, recurrent laryngeal nerve, or even the superior vena cava. Blood supply of the thyroid is via the superior and inferior thyroid arteries; venous drainage is more variable but usually there are paired superior, middle, and inferior thyroid veins.

Histologically, thyroid tissue is composed of spherical thyroid follicles. Each follicle consists of a single layer of cuboidal follicular cells surrounding a lumen filled with a homogenous material called colloid. With stimulation, the follicular cells become columnar and the follicles are depleted of colloid; with suppression, the follicular cells become flat and colloid accumulates. The thyroid also contains parafollicular C cells which produce calcitonin. 

Thyroid Hormone Synthesis and Secretion

Synthesis of T4 and T3 by the thyroid gland involves 6 major steps: active transport of iodide across the basement membrane into the thyroid follicular cell (iodide trapping), oxidation of iodide and iodination of tyrosyl residues in thyroglobulin, coupling of iodotyrosine molecules within thyroglobulin to form T3 and T4, proteolysis of thyroglobulin with release of free iodotyrosines and iodothyronine, deiodination of iodotyrosines within the follicular cell with conservation and reuse of the liberated iodide, and, under certain circumstances, intrathyroidal deiodination of T4 to T3.

The T3 and T4 released from the thyroid by proteolysis reach the bloodstream where they are bound to thyroid hormone binding proteins. The major thyroid hormone binding protein is thyroxine binding globulin (TBG) which normally accounts for 75% of the bound hormone. All of the circulating T4 is produced by the thyroid; whereas, 20% of T3 is produced by the thyroid and the rest is produced by peripheral deiodination of T4 at extrathyroidal sites. T3 is by far the most active thyroid hormone. Peripheral deiodination of T4 can also result in reverse T3, a largely inactive thyroid hormone.

All reactions necessary for the production of T3 and T4 are positively influenced by thyroid stimulating hormone (TSH). Pituitary TSH secretion is controlled by a negative feedback mechanism modulated by the circulating levels of free T4 and free T3. Increased levels of free T4 and free T3 inhibit release of TSH and decreased levels of free T4 and free T3 stimulate release of TSH. Thyrotropin releasing hormone (TRH), synthesized by the hypothalamus also influences the secretion of TSH. When TRH is released into the portal system between the hypothalamus and pituitary, it causes release of TSH from anterior pituitary thyrotropic cells. The precise regulation of TRH synthesis and release has not been completely elucidated although T4 and T3 play a role.

An adequate supply of iodine is essential to normal levels of thyroid hormone production. The recommended minimum intake of iodine is 150 micrograms a day; intake of less than 50 micrograms a day is associated with goiter. High iodine levels inhibit iodide oxidation and organification; iodine excess inhibits thyroglobulin proteolysis (this is the principal mechanism for the antithyroid effect of inorganic iodine in patients with thyrotoxicosis).

Effects of Thyroid Hormones

1. Fetal brain development and skeletal maturation are dependent of fetal thyroid hormone production. In the absence of fetal thyroid hormone secretion, cretinism results (mental retardation and dwarfism).

2. T3 increases oxygen consumption and heat production which contributes to increased basal metabolic rate and the increased sensitivity to heat in hyperthyroidism and increased sensitivity to cold in hypothyroidism.

3. T3 stimulates transcription of myosin heavy chain alpha and inhibits transcription of myosin heavy chain beta, improving cardiac muscle contractility. T3 also increases transcription of calcium ATPase in the sarcoplasmic reticulum, alters isoforms of sodium-potassium ATPase genes, and increases beta-adrenergic receptors and the concentration of G proteins. Thus, thyroid hormones have significant positive inotropic and chronotropic effects on the heart.

4. Thyroid hormones increase the number of beta-adrenergic receptors in heart muscle, skeletal muscle, adipose tissue, and lymphocytes. Sensitivity to catecholamines is markedly increased in hyperthyroidism and treatment with beta-blockers may be helpful in controlling tachycardia and arrhythmias.

5. Thyroid hormone stimulates gut motility which can result in diarrhea in hyperthyroid states and constipation in hypothyroidism.

6. Thyroid hormone increases bone turnover. Bone resorption is increased more than bone formation which may result in significant osteopenia in chronic hyperthyroidism.

7. Thyroid hormone stimulates hepatic gluconeogenesis and glycogenolysis as well as intestinal absorption of glucose. This results in increased serum glucose. Thyroid hormone also causes increased cholesterol synthesis and degradation as well as increased lipolysis. This results in a lowering of serum cholesterol.

Diffuse and Multinodular Goiter

Multinodular goiter is one of the most common endocrine diseases worldwide, affecting 500-600 million people. Multinodular goiter is more prevalent in areas where iodine is lacking in the diet. In iodine deficient areas, hypothyroidism results with an increase in TSH. Increasing TSH causes growth of the thyroid gland and the development of diffuse nontoxic goiter. With growth of the thyroid gland, thyroid function often becomes autonomous, that is, thyroid hormone secretion becomes independent of TSH secretion. Multinodular goiters evolve from diffuse goiters. One or more follicles will have greater intrinsic growth and functional capability and continue to grow and function despite declining TSH secretion causing first a nontoxic multinodular goiter and ultimately a toxic multinodular goiter. Though usually associated with iodine deficiency, multinodular goiter also occurs in populations whose diets are iodine replete; this suggests other factors such as genetic influences may play a role in development of multinodular goiter. A gene located on chromosome 14q, MNG-1, has been associated with familial nontoxic multinodular goiter and polymorphism of codon 727 has been associated with toxic multinodular goiter.

Most commonly, the patient with multinodular goiter is unaware of any problem until the diagnosis is made during a routine physical exam or evaluation for another problem. Patients with longstanding multinodular goiter are more likely to develop clinical or subclinical thyrotoxicosis. Patients may be referred to the otolaryngologist for compressive symptoms or suspicion of malignancy. Symptoms of tracheal compression include dyspnea, stridor, cough and choking sensations. Initially mild tracheal compression is asymptomatic. When tracheal compression becomes more significant, dyspnea and stridor develop. In those patients with a substantial intrathoracic component to their goiter, dyspnea and stridor may be nocturnal or positional, occurring primarily during maneuvers that force the thyroid into the thoracic inlet such as reaching. Compression of the jugular or subclavian veins or superior vena cava results in facial plethora and dilated neck veins. Pemberton’s maneuver, elevation of both arms until they touch both sides of the head for one minute, may demonstrate congestion, cyanosis or facial discomfort. Vocal cord paralysis, usually transient, can occur secondary to stretching or compression of one or both recurrent laryngeal nerves. Rapid, painful growth of a nodule may represent hemorrhage into a degenerating colloid nodule; if this occurs in an intrathoracic nodule, acute airway obstruction may occur. FNA may be indicated in patients with fast-growing or dominant nodules and nodules with a firmer consistency than other nodules within the same gland.

Workup includes laboratory studies such as TSH, T4 and T3 to determine the functional status of the thyroid. Diffuse or nodular goiter may be investigated with pulmonary function tests if tracheal compression is suspected; flow-volume loop tracings may be abnormal even in patients who are asymptomatic. CT and MRI are highly sensitive methods for detecting tracheal compression or intrathoracic extension of a goiter. If administration of iodinated contrast is necessary, pretreatment with antithyroid drugs may be recommended to avoid acute thyrotoxicosis.

Grossly, the thyroid gland in multinodular goiter consists of nodules that vary in size and shape. Histologically, multinodular goiters contain follicles of various sizes lined by cuboidal or flat epithelium; foci of hemorrhage and chronic inflammation are present. Larger nodules can develop pseudocapsules that usually incompletely encapsulate and merge into surrounding stroma.

Suppression therapy is the administration of thyroid hormone in order to suppress TSH and decrease the size of the goiter. This therapy has met with variable success and includes a risk of inducing thyrotoxicosis if the thyroid nodularity has been functioning independently. The efficacy of this approach is controversial. One study showed a mean 25% decrease in size of goiter at 4 months; although, when treatment was discontinued, thyroid size returned to baseline. Best results are obtained with small goiters. Suppression is associated with a risk of cardiac arrhythmias and osteopenia if the suppression is prolonged. These risks are greatest in the elderly population.

Medical treatments may also include antithyroid drugs such as propylthiouracil and methimazole. These drugs can normalize thyroid hormone levels in patients with toxic multinodular goiter. Long term treatment is considered safe. Side effects of antithyroid drugs include rash (5%) and agranulocytosis (0.5%). Rash can usually be managed with antihistamines and does not require cessation of therapy. Agranulocytosis is a serious side effect which is often heralded by a fever and sore throat. It requires cessation of therapy, appropriate antibiotic therapy, and shifting to an alternative therapy.

Radioiodine (I-131) is another treatment option for patients with both toxic and nontoxic multinodular goiter. It can reduce the size of the goiter and decrease the presence of hyperthyroidism. This treatment modality has been shown to reduce the size of toxic and nontoxic multinodular goiter by approximately 40-60% in 2 years. Return to euthyroid state is dose dependent and in one study 88% of patients treated were euthyroid at 5.2 years follow up. Disadvantages of I-131 include the possible need for more than one treatment, delayed effects, risk of hypothyroidism or the development of Graves’ disease, and it is contraindicated in pregnant women or women who want to become pregnant in the next year.

Surgical therapy for nontoxic goiter may be necessary in extremely large goiter, suspicion of malignancy, tracheal or esophageal symptomatology, substernal extension, vocal cord paresis, or rapid growth. Nontoxic multinodular goiter can be treated with either total thyroidectomy or subtotal thyroidectomy; this will provide pathologic confirmation, avoidance of radiation, one-stage treatment and low risk of recurrence. Toxic multinodular goiter is commonly treated with subtotal or total thyroidectomy.

Prior to treatment with radioactive iodine or surgical treatment, patients with toxic multinodular goiter need pretreatment cardiac evaluation and medical management as indicated. This will often include the need for antithyroid medications, beta-blockers, and potassium iodide. If possible, it is recommended to treat the patient until he is euthyroid and any cardiac problems are well controlled. When nonsurgical treatment options are selected, it is recommended that patients undergo serial examinations with thyroid laboratory evaluation and ultrasound as needed to identify any enlarging or dominant nodules that pose a risk of malignancy.

Graves’ Disease

Graves’ disease is the most common form of thyrotoxicosis. This syndrome consists of one or more of the following features: thyrotoxicosis, goiter, ophthalmopathy, dermopathy. It has an autoimmune etiology and a strong familial predisposition; approximately 15% of patients with Graves’ disease have a close relative with the disorder and approximately 50% of relatives of patients with Graves’ disease have circulating thyroid autoantibodies. Females are diagnosed with Graves’ disease five times more often than males; the peak age at diagnosis is 20 to 40 years of age. In Graves’ disease, T lymphocytes become sensitized to thyroid antigens and stimulate B lymphocytes to synthesize antibodies to these antigens. Thyroid autoantibodies, TgAB and TPO Ab, are found in both Hashimoto’s and Graves’ disease; TSH-Rab[stim] is unique to Graves’ disease. This autoantibody binds to the TSH receptor and stimulates the gland into hyperfunction. Triggers to acute episodes of Graves’ disease include: pregnancy and the postpartum period, iodine excess, lithium therapy, viral or bacterial infections and glucocorticoid withdrawal.

In young patients first presenting with Graves’ disease, symptoms are those of thyrotoxicosis including: palpitations, nervousness, easy fatigability, diarrhea, excessive sweating, intolerance to heat and preference for cold. There can be marked weight loss in the face of hyperphagia. Thyroid enlargement, eye signs and mild tachycardia may be present. In older patients, the clinical picture usually includes cardiovascular and myopathic manifestations; commonly, the patients complain of palpitations, dyspnea on exertion, tremor, nervousness and weight loss.

The development of Graves’ ophthalmopathy may involve cytotoxic lymphocytes sensitized to a common antigen such as TSH-R found in orbital fibroblasts, orbital muscle and thyroid tissue. Graves’ ophthalmopathy involves orbital myositis with swollen orbital muscles, proptosis of the globes and diplopia as well as redness, and periorbital edema. The American Thyroid Association has set forth a classification of eye signs. Class one involves spasm of the upper lids associated with active thyrotoxicosis; class two is characterized by soft tissue involvement with periorbital edema and chemosis; class three is proptosis as measured by Hertel exophthalmometer; class four is extraocular muscle involvement, most commonly the inferior rectus which limits upward gaze; class five is characterized by corneal involvement; class six is loss of vision due to optic nerve involvement.

Grossly, the thyroid gland is symmetrically enlarged. Histology of the thyroid gland reveals follicles lined with tall columnar cells with basally located nuclei. Colloid adjacent to epithelium appears vacuolated and scalloped. Some follicles contain almost no colloid. The stroma contains lymphocytes. The follicular epithelium often projects into the lumen of the follicles the form of small papillary infoldings.

Treatment of Graves’ disease may involve antithyroid drugs, surgery or radioactive iodine. Graves’ disease can be treated with antithyroid drugs such and propylthiouracil and methimazole. The duration of therapy is quite variable and can range from 6 months to 20 years or more. Remission may occur in 20-40% of patients treated for 6 months to 15 years; incidence of relapse is as high as 50-60%.

I-131 is an option for treating patients with Graves’ disease. This radioactive iodine is an excellent method for destroying overactive thyroid tissue. Rates of subsequent thyroid cancer, leukemia or other malignancies have not been shown to be increased in patients treated with I-131, and children born to parents previously treated with radioactive iodine show normal rates of congenital abnormalities. Radioactive iodine is absolutely contraindicated in pregnant women as radiation is harmful to the developing fetus. Following I-131 therapy, ophthalmopathy worsens or appears in a significant proportion of patients; this can be controlled with three months of treatment with prednisone post-radiation.

Surgical treatment consists of subtotal or total thyroidectomy. This is usually offered to patients with very large or symptomatic goiters, those who cannot tolerate or do not respond well to drug therapy, and those with severe or progressive ophthalmopathy. Prior to surgery, an attempt is made to bring the patient to a euthyroid state. Also, potassium iodide can be given two weeks prior to surgery to diminish vascularity of the gland and simplify surgery.

Complications of Graves’ disease include acute thyrotoxicosis and thyroid crisis (thyroid storm). Acute thyrotoxicosis may be managed with beta-blockers such as propranolol to control tachycardia, hypertension and atrial fibrillation. Barbiturates such as phenobarbital accelerate T4 metabolism and may be helpful for its sedative effect and to lower T4 levels. Cholestyramine will lower serum T4 by binding it in the gut. Thyroid storm is an extreme form of thyrotoxicosis which is relatively rare today. Patients present with delirium, severe tachycardia, vomiting, diarrhea, dehydration, and high fever. The mortality rate is high.

Toxic Adenoma

An autonomously functioning thyroid nodule that hypersecretes T4 and T3 is called a toxic adenoma. This can lead to clinical or subclinical thyrotoxicosis. The etiology of toxic adenoma is related to iodine deficiency as comparison of rates of development of toxic adenoma between populations in which dietary iodine is relatively replete versus relatively lacking show higher rates of toxic adenomas in populations that have lower dietary iodine. Commonly, the patient is an individual over 40 who has noticed the growth of a longstanding thyroid nodule. Women are diagnosed with toxic adenoma six times more often than men. Symptoms of hyperthyroidism may be noted. The natural history of toxic adenoma has been extensively studied; a German study of 375 euthyroid patients with toxic adenoma followed for 17 years showed 18% became hyperthyroid. Tendency to become hyperthyroid is age related with younger patients having a lower chance and older patients having a higher chance of becoming hyperthyroid. Nodules that produce thyrotoxicosis are virtually always greater than 3 cm in diameter. Laboratory studies show suppressed TSH and marked elevation of T3 levels, often with only borderline elevation of T4. Toxic adenomas are almost never malignant. They can usually be managed by antithyroid drugs; however, these medications do not inhibit the proliferative effects of the cellular defect. Thus, the nodule will usually continue to increase in size and more definitive therapy such as I-131 or unilateral lobectomy may be pursued.

Chronic Thyroiditis

               

Chronic thyroiditis (aka Hashimoto’s thyroiditis or lymphocytic thyroiditis) is likely the most common cause of hypothyroidism and goiter in the United States. Chronic thyroiditis is thought to result from lymphocytes becoming sensitized to thyroidal antigens; autoantibodies are formed which react to these antigens. Autoantibodies include thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb) formerly called microsomal antibody, and TSH receptor blocking antibody (TSH-Rab[block]). During the early phase of chronic thyroiditis, TgAb is markedly elevated. Later, TgAb may disappear, but TPOAb may be detectable for many years.

The gland is heavily infiltrated with lymphocytes destroying normal thyroid architecture. Lymphoid follicles and germinal centers may be present. Follicular epithelial cells are frequently enlarged and contain basophilic cytoplasm (Hurthle cells). Destruction of thyroid parenchyma results in a fall in serum T3 and T4 and a rise is TSH. Increases in TSH may maintain adequate hormone synthesis by the development of thyroid parenchyma hypertrophy; occasionally, the gland fails and permanent hypothyroidism with or without goiter results.

Chronic thyroiditis may present as a goiter in a euthyroid patient or a patient with mild hypothyroidism. Gender distribution is four females to one male. As the process of thyroid destruction and enlargement is painless, patients may be unaware of the goiter unless it becomes very large. Where only 10-15% of young patients presenting with chronic thyroiditis develop permanent hypothyroidism, older patients with chronic thyroiditis have a much higher incidence of permanent hypothyroidism. Therapy with levothyroxine will cause regression of the goiter and treat the hypothyroidism. Occasionally, patients with chronic thyroiditis will have periods of thyrotoxicosis when large amounts of T3 and T4 are released as gland parenchyma is destroyed.

Subacute Thyroiditis

Subacute thyroiditis (also known as De Quervain’s thyroiditis) is the most common cause of thyroid pain and tenderness. It is an acute inflammatory disorder of the thyroid gland most likely due to viral infection. Suspected viral agents include mumps virus, cocksackie virus, and adenovirus. It usually affects patients in the 4th and 5th decades with a female to male ratio of 5 to 1. The incidence of subacute thyroiditis tends to be seasonal and geographic, coinciding with seasonal enterovirus infections. Histologic evaluation reveals destruction of thyroid parenchyma and the presence of many large phagocytic cells, including giant cells and granulomatous changes. Microabscesses and fibrosis may also be present. These changes revert to normal or minimal fibrosis when the disease subsides.

Patients with subacute thyroiditis present with fever, malaise, and soreness in the neck which may extend to the angle of the mandible or toward the ear lobes on one or both sides of the neck. The thyroid can be slightly to moderately enlarged; this enlargement is usually diffuse with the thyroid being firm in consistency but occasionally being quite hard. Initial features may be those of hyperthyroidism including palpitations, agitation and sweats. Unlike Graves’ disease, there is no ophthalmopathy. The thyroid gland is tender to palpation, sometimes exquisitely so. Laboratory studies during the initial phase of the illness will show elevations of T3 and T4 with suppression of TSH. Radioactive iodine uptake will be decreased and there will be an elevation in serum thyroglobulin. Thyrotoxicosis in subacute thyroiditis is the result of tissue injury followed by the release of large amounts of thyroid hormone into the circulation. ESR may be as high as 100 mm/h. Usually, thyroid autoantibodies are not present.

As the disease progresses and the patient begins to show signs of hypothyroidism, T4 and T3 will drop and TSH will rise. Thus, patients with subacute thyroiditis usually have a transient period of hypothyroidism. Subacute thyroiditis usually remits spontaneously over weeks to months. Relapses may occur when the T4 levels have fallen, TSH has risen and the gland is starting to recover function. Uncommonly, the course may extend over several years, with repeated bouts of inflammatory disease. Treatment is usually symptomatic and may consist of a course of NSAIDS or a glucocorticoid such as prednisone if pain, fever and malaise are disabling. Beta-blockers may be used if signs and symptoms of thyrotoxicosis are severe. Antithyroid drugs have no role because thyroid hormone biosynthesis is already low. Levothyroxine is indicated during the hypothyroid phase in order to prevent exacerbation of the disease induced by rising TSH levels. Permanent hypothyroidism results in approximately 5-10 % of cases.

Other causes of anterior neck pain must be differentiated from subacute thyroiditis. These causes include hemorrhage into a thyroid nodule or cyst and acute suppurative thyroiditis. In both cases, radioactive iodine uptake studies show normal function of the unaffected areas of the gland. In acute suppurative thyroiditis, patients have greater leukocytosis, higher fever, more inflammation of surrounding tissues and a septic focus elsewhere in the body is usually evident.

Riedel’s Thyroiditis

Reidel’s thyroiditis is a rare disorder in which fibrous tissue replaces thyroid tissue. This disease usually occurs in middle-aged women and has a likely autoimmune etiology. Signs and symptoms of Riedel’s thyroiditis include the development of a rapidly enlarging, hard neck mass which may be associated with tracheoesophageal compression, suggesting the possibility of poorly differentiated thyroid cancer or thyroid lymphoma. Riedel’s thyroiditis is associated with other fibrosclerotic conditions such as retroperitoneal fibrosis and sclerosing cholangitis. In fact, within ten years of diagnosis, approximately 30% of patients develop retroperitoneal or mediastinal fibrosis. FNA or open biopsy may be needed to differentiate this entity from cancer. Treatment is focused on relief of obstruction and, to that effect, surgery may be necessary to relieve tracheal compression. Medical treatment with glucocorticoids and, more recently, tamoxifen has been employed with some success. Patients are initially euthyroid but later develop hypothyroidism as glandular tissue is replaced by fibrosis.

BENIGN THYROID DISEASE

Surgical literature is replete with discussions of surgical interventions and operative details of thyroid diseases. However, patients may present to the head and neck surgeon with thyroid diseases which require knowledge of thyroid physiology and endocrinology for diagnosis. In addition, it is incumbent upon any surgeon wishing to pursue surgery on the endocrine glands to understand the spectrum of diseases which may occur, and current alternative methods to treat these conditions. This will ensure both the best treatment for the patient, and help facilitate better understanding between the endocrine surgeon and the primary physician. This discussion is meant as an overview of thyroid physiology, and a brief discussion of common diseases of the thyroid gland which may present primarily to the head and neck surgeon or complicate surgical therapy of the thyroid gland.

History

The thyroid gland has long been recognized in medical literature due to the development of goiter in iodine deficient areas. The first description of thyroid goiter dates back to China around 2700 BC. Although it was recognized anatomically for centuries, the knowledge of its function was purely speculative. Da Vinci postulated that the gland was designed to fill a vacant space within the neck region. Parry believed that the heavy vascularity of the gland served as a buffer to prevent spikes in blood flow to the brain from the heart. Other physicians postulated the gland was used in lubrication of the neck tissues, or was an indicator of puberty. It was not until the practice of thyroidectomy became standard after the techniques of Bilroth, Kocher, and others, that the function of the thyroid became apparent. Kocher and other surgeons noted retrospectively that total thyroidectomy patients developed myxedema and cretinism. At this time, Halstead also noted a difference in the incidence of myxedema and tetany between Bilroth and Kocher. Bilroth usually performed a more rapid and bloody excision, but often left portions of the thyroid gland. His patients occasionally developed tetany, but rarely myxedema. Kocher used a more bloodless technique, excising the entire gland on its capsule. He rarely had cases of post-operative tetany, but had a higher incidence of myxedema. The cause of post-operative tetany was finally discovered in 1891 by Eudene Gley, who attributed this to parathyroid removal. While surgical advances were leading to great improvements in the survivability of thyroid procedures, advances in knowledge of thyroid function and diseases were also being made. In the 1820’s it was discovered that the use of seaweed (iodine) lead to a decrease in goiter size, and in the 1830’s, the disease we now refer to as Graves’ disease was first described. These rapid advances into the later half of the 19th century made our current understanding of thyroid diseases and treatments possible.

 

Thyroid Physiology

The thyroid gland is made up of cells arranged into follicles. Each of these cells takes up inorganic iodine through a Sodium/Iodine symporter. This process in stimulated by TSH. Once the iodine is within the cell, thyroid peroxidase, an apical membrane protein, catalyzes a reaction to organify the iodine and move it into the follicular space (colloid). While in this space, thyroid peroxidase (TPO) also catalyzes a reaction which links two of these molecules together, thus forming T3 and T4. These two steps which utilize TPO are important, because they are the site of function for the anti-thyroid medications PTU and methimazole, both of which inactivate TPO. After hormone production, it is kept in the colloid until a stimulus (TSH) induces its release. The hormone is then endocytosed, the excess protein is removed, and then the hormone is secreted into the bloodstream. This release step is also affected by the medication lithium, and when taken chronically, can lead to goiter due to inability to release stored hormone.

In areas of normal iodine intake, this cycle occurs without problems. However, if the thyroid is suddenly given a large bolus of iodine, several effects may occur. First, the thyroid may begin to produce and store more hormone; but as the iodine builds up within the gland, it actually causes the thyroid to stop producing more hormone. This is known as the Wolff-Chaikoff effect. In some instances, this can lead to chronic suppression of thyroid hormone formation, and result in goiter. If the patient has an underlying hyperthyroid disorder where the gland is chronically stimulated, such as Graves’ disease, then a bolus of iodine may have an opposite effect, and stimulate a sudden increase in the formation and release of hormone leading to thyrotoxicosis. This is known as the Jod-Basedow phenomenon.

Thyroid hormones are controlled through a feedback inhibition model, where the final product, T3, inhibits the release of thyrotropic factors. The initiating factor in the cascade is TRH, which is produced in the hypothalamus. This then stimulates the release of TSH. However, the release of TSH is influenced more by the circulating T3 levels than the TRH. Once TSH is produced, it then acts at on the thyrocytes directly to stimulate growth, iodine uptake, and colloid endocytosis. Once the colloid is endocytosed and released, it circulates as T3 and T4, with 98% of the hormone in circulation being T4. The hormones then circulate in the serum in bound and free components. The bound component comprises the vast majority of circulating hormone, and the binding proteins include thyroid binding globulin, transthyretin, and albumin. Changes in the concentrations of these proteins, such as in liver failure, can alter the total amount of hormone circulating in the system. This occurs because the body regulates the free component of the hormone, and the free/total ratio remains the same, regardless of total hormone in circulation. This is why certain disease states necessitate measurement of the free T3 and T4 rather than the total values. Medications such as anticonvulsants can also compete for the binding sites of thyroid hormones, causing displacement of hormone, and thus give a false impression of thyroid function.

When assessing thyroid function, the most practical method is measurement of the TSH level, since this is indicative of the thyroid state. If the TSH results are abnormal, or if clinical exam is suggestive, then T3 and T4 levels (total or free) can be obtained to further delineate the exact thyroid state. TRH levels or stimulation tests are rarely needed due to the rarity of central axis thyroid dysfunction.

Goiter

The term goiter refers to a chronic enlargement of the thyroid gland. This condition is frequently broken down into endemic goiter and sporadic goiter. Endemic goiter is strictly defined as goiter in a region where >5% of children age 6-12 have a goiterus condition. Sporadic goiter occurs is defined as goiter occurring in any area where the incidence is less than 5% of children 6-12 years. Areas of endemic goiter include china and central Africa, and are commonly due to iodine deficiency.

There are multiple causes of goiter. Hashimoto’s thyroiditis can cause a goiter in its early stages, but usually results in an atrophic gland in the later stages. Graves’ disease commonly results in goiter due to excess stimulation of the TSH receptor. Certain diets that are high in cabbage, broccoli, or cassava can lead to goiter. In addition, chronic ingestion of high doses of iodine (seaweed) can lead to thyroid enlargement, as can chronic use of lithium.

Once goiter is diagnosed, the status of the thyroid function should be assessed, since it can greatly impact the treatment recommended. If a patient is found to have a low TSH, they can be grouped as having clinical hyperthyroidism (low T3, T4), or subclinical hyperthyroidism (normal T3, T4). Both conditions may require treatment due to the long-term effects of hyperthyroidism, which include the risk of atrial fibrillation, congestive heart failure, and bone loss.

If the patient has goiter with normal thyroid functions, this condition is simply termed non-toxic goiter. For these patients, which usually have a multinodular goiter, the workup for cancer should be performed just like any solitary nodule. The nodule size should be measured and followed. FNA is recommended once the nodule increases >1.5 cm, while nodules >4cm are difficult to asses and require definitive treatment. If a nodule less than 4cm is found to be normal, then simple yearly follow-up with ultrasound to detect enlargement can be done. When the goiter does not cause compression, periodic observation is usually the treatment of choice. However, if the patient has any risk factors for carcinoma, such as rapid enlargement, history of radiation, suspicious neck lymphadenopathy, or papillary carcinoma on FNA, then surgery may be indicated. Thyroid suppression therapy for benign non-toxic goiter is not commonly done due to the high dose of thyroid hormone needed, and the rapid recurrence of the goiter following withdraw of therapy. If symptoms of compression are present, treatment is indicated. The most common treatment for compressive non-toxic goiter is surgery. This rapidly reverses the symptoms, and avoids the complications of ablation. For patients that are not as healthy or that opt for ablation, I131 may be given. The treatment reduces the gland size by 33% – 66% in most patients, and the symptoms improve in 70%-90%. However, radioactive iodine for a non-toxic goiter can result in permanent hypothyroidism in up to 80% of patients, and post-RAI Graves’ disease in 10%.

For patients with thyroid goiter and hyperthyroidism, the term toxic goiter is used. These conditions may include Graves’ disease, toxic adenoma, thyroiditis, or recent administration of iodine. For toxic conditions, FNA evaluation is not needed for treatment planning, since hyperactive nodules often mimic follicular neoplasms on FNA, and have a low potential for malignancy. In clinical or subclinical hyperthyroid conditions, the disease warrants treatment due to the risks for atrial fibrillation, heart failure, and bone loss. For toxic multinodular goiter, the preferred treatments are surgery and radioiodine. Anti-thyroid medications are not recommended for long-term use due to their side effects, such as agranulcytosis. Treatment with radioiodine may reduce the gland size by 40% within the first year, and the risk of post RAI ablation is only 11% – 24% for toxic goiter. Some patients will require a second dose if a problem persists. Surgery is also a viable option; however, the risk for post-operative hypothyroidism in subtotal thyroidectomy is higher that RAI, so RAI is often the first line of treatment. Patients that are undergoing surgery should have their hyperthyroid symptoms controlled prior to treatment with a short course of methimazole or PTU.

If the patient has toxicity due to Graves’ disease, then the treatment recommendations may differ. Since Graves’ disease has a chance for remission, most recommend beginning a non-ablative therapy initially. This is commonly done with methimazole or PTU. These medications will control the hyperthyroidism, and may be stopped after several months to check for disease remission, which may occur in 40% – 60%. Complications of therapy, such as agranulocytosis should be monitored for during therapy. RAI may also be employed. This therapy is usually effective, but it is also permanent, with a 55% – 75% incidence of hypothyroidism which requires lifetime hormone therapy. RAI must be avoided in children or pregnancy. Surgery is also an option, but is usually reserved for goiters that are too large for RAI, or goiters in children or goiters with compressive symptoms. The hypothyroid rate for surgery is almost equal to the RAI rate for this condition.

Hyperthyroidism and goiter may also be due to a large gland with a solitary hyperfunctioning adenoma. This condition is much less common than Graves’ or toxic MNG, but requires treatment due to the same risks of hyperthyroid states. In general, nodules <3cm do not require treatment since they are usually asymptomatic. Treatment with anti-thyroid medications is not advised due to their complications. Radioactive iodine is recommended and has a low hypothyroidism rate due to selective nodule uptake. Surgery can be done, but is generally reserved for adolescents or pregnant patients. For patients who have severe toxic symptoms, these should be controlled with a short course of anti-thyroid medications prior to RAI or surgery. 

Thyroiditis

For patients with hypothyroidism, there are several common causes depending on the geographic origin of the patient. For people in iodine deficient areas of the world, iodine deficiency is the most common cause of hypothyroidism. However, for people in industrialized nations, the most common cause is from some form of thyroid destruction, due to Hashimoto’s disease, surgery, or radioactive iodine. If the patient’s history is negative for surgical conditions or radioactive iodine administration, then Hashimoto’s disease is the most common cause in the U.S. This involves a painless enlargement of the thyroid gland initially, but later results in a painless atrophic gland. Thyroid functions show a high TSH, and a low or normal T3, T4.

Patients may also have demonstrable antibodies to TPO or TBG. Treatment involves thyroid hormone replacement with levothyroxine for most patients. Treatment with T3 may be needed for patients with myxedema.

Several other forms of thyroiditis also occur, however, with much less frequency than Hashimoto’s disease. Most of these diseases involve several phases. The first phase may involve a hyperthyroid state due to acute inflammation of the thyroid gland with release of pre-formed hormone. The next phase usually involves a period of resolution as the gland recovers from the inflammation and the patient exhibits euthyroidism. Some patients then progress to a hypothyroid state while the gland recovers from the insult, and final resolution to a euthyroid state may take up to a year.

Silent thyroiditis is one of these inflammatory conditions. It occurs spontaneously, and may be termed post-partum thyroiditis if it occurs within one year of delivery. Thyroid functions are initially elevated, and patients often present with hyperthyroidism and a non-tender gland on exam. Treatment is usually supportive, with beta blockers for symptoms. Severe toxicity may require iodine administration. The resolution phase may be prolonged requiring treatment with thyroid hormones for up to a year.

Subacute thyroiditis is similar in course to silent thyroiditis. However, the presentation of this disease is its defining element. These patients present with acute hyperthyroidism and a painful enlarged thyroid gland. Patients often need beta blockers for symptoms, and may require iodine if severe symptoms develop. Treatment involves salicylates or steroids for severe swelling and pain. Pain and symptoms generally resolve within a few weeks, and most people will return to normal thyroid function within a year.

Acute thyroiditis is an uncommon condition that also presents with a painful thyroid. This condition involves an acute infection of the thyroid gland itself. It may be related to an infection of the deep neck spaces, or a pyriform sinus fistula. Regardless of the cause, it requires hospital admission and IV antibiotic therapy on diagnosis. Failure to diagnose and treat this disease in a timely fashion is associated with a high mortality rate. FNA can be done if clinical abscess is present, or to obtain a culture to guide treatment. At some point in the treatment course, a barium swallow or direct laryngoscopy is recommended due to the frequency of pyriform sinus fistula with this condition. If treated promptly, most cases return to normal function after the insult.

The least common of all thyroiditis conditions is termed Reidel’s thyroiditis. This entity involves a replacement of the thyroid gland with dense scar tissue creating a gland with the consistency of hard wood. Patients may complain of pain or dysphagia as the gland enlarges, and may progress to hypothyroidism is the gland is replaced by scar. This syndrome is associated with other focal sclerosis syndromes such as retroperitoneal fibrosis. Treatment involves open biopsy for diagnosis, surgical debulking for compressive symptoms, and thyroid hormone for hypothyroidism. The main therapy for this disease is chemotherapy utilizing tamoxifen or methotrexate to prevent recurrence.

Conclusions

Thyroid disease is common in clinical practice. It is important for any surgeon who wishes to treat thyroid disorders to understand the common problems associated with the thyroid gland, and the medical or surgical therapy that each disorder entails. This will improve understanding and communication between the endocrinologist and surgeon, since most operative patients will need to be followed for life. In addition, thyroid disorders may present primarily to head and neck surgeons with complaints of neck pain or dysphagia. It is important that these patients are properly diagnosed, and that the indications for surgical and medical therapy are well understood.

THYROID CANCER

History

In 1812, Gay-Lussac discovered the element iodine as a factor caused goiter. By 1833, Boussingault prescribed iodized salt for prevention and treatment of goiter. In 1836, T.W. King, an English morphologist, presented descriptions of the thyroid follicle, its lymphatic and blood supply, and some predicted theories about the nature of colloid. In the 1870s, Fagge demonstrated the absence of thyroid function causes sporadic and congenital cretinism. William Gull and William Ord clarified the clinical and pathological role of the thyroid in myxedema.

The biggest contribution was from Theodor Kocher, a skillful surgeon from Bern, Switzerland. Kocher’s technique became popular and was published widely. By 1882, Kocher’s mortality rate was 2.4% and by the end of the 19th century this rate was as low as 0.18%. Kocher had over 5000 cases by the time of his death in 1917. Billroth added the bilateral partial resection technique to prevent hypothyroidism, nerve paralysis, and hypoparathyroidism (tetany). William Stewart Hallsted absorbed the thyroidectomy techniques of Billroth and Kocher and created his own skills of the thyroid resection in the United States since 1880. He was a pioneer American surgeon, who presented the techniques of thyroidectomy to its standard procedure by the time of his death in 1922.

Thyroid cancer was first described by Halsted in his extensive compilation of documented thyroidectomies by the terms sarcomatous degeneration, thyroid tumor or thyroid cancer cells. He described thyroid cancers as the silent growths, even though these sleeping tumors can suddenly became more aggressive, metastasize, recur and transform into highly lethal or high mortality cancers.

Anatomy

The thyroid gland is the first endocrine gland to form in the human embryo. In the fourth week, it begins as a thickened median endodermis caudally to the later site the median tongue bud. It then migrates anteriorly and inferiorly onto the hyoid bone and laryngeal cartilages, through the thyroglossal duct. At the end of fifth week, the duct breaks down and the thyroid gland continues descending to its position, anterior to the trachea, by the seventh week. The thyroglossal duct then normally disappears by the tenth week.

The thyroid gland locates deep to the sternohyoid muscle, from the level C5 to T1 vertebrae or anterior to the 2nd and 3rd tracheal rings. It consists of two lobes, connected in the middle by a narrow isthmus, which is conical or pyramidal shape. In 50% of population, thyroid gland may stay as high as the level of the hyoid bone. Each lateral lobe is attached to the trachea by a consolidated connective tissue called the lateral suspensory (Berry) ligament. The posterior extensions of the each thyroid lobe are the tubercles of Zuckerkandl, which have an important relationship to the recurrent laryngeal nerve.

The thyroid gland was supplied by four main arteries:

(1) The superior thyroid arteries (paired) originate from the external carotid artery (the first or second branch) or the common carotid artery. When it approaches the thyroid gland, the superior thyroid artery divides into anterior and posterior branches, which will then distribute numerous small branches to the gland and join with their counterparts from the opposite side.

(2) The inferior thyroid arteries (paired) arise from the thyrocervical trunk and ascend into the neck on the medial aspect of the anterior scalene muscle, deep to the prevertebral fascia and cross vertically to the ascending recurrent laryngeal nerve. The inferior thyroid artery divides further into two branches: the upper branch supplies to the posterior aspect of the gland and the lower branch supplies to the lower pole of the gland.

In 1.5% to 12% of the cases, the thyroid ima artery, a variation of the inferior thyroid artery, may present usually in right side and ascend in front of the trachea. The superior and middle thyroid veins drain to the anterior facial vein and internal jugular vein. The inferior thyroid vein and thyroid ima vein form the innominate vein and drain into the branchiocephalic vein. The recurrent laryngeal nerves are close to the thyroid globes and the inferior thyroid arteries.

The lymphatic vessels of the thyroid gland drain into the internal jugular chain, the pericapsular region, the prelaryngeal, pretracheal and paratracheal lymph nodes. The lateral lymphatic vessels located along the superior thyroid vein pass to the inferior deep cervical lymph nodes such as retropharyngeal and retroesophageal areas. Nerve innervation of the thyroid gland is from the superior, middle, and inferior cervical sympathetic ganglia, which form the cardiac, and superior and inferior thyroid periarterial plexuses.

Physiology

Three components participate in the euthyroidism control:

(1) Thyroid gland responsible for the synthesis, storage, and secretion of thyroxine (T4) and 3,5,3’-triodothyronine (T3: the most potent biologic agent).

(2) The peripheral control of the T3, T4 metabolism, after their release into the circulation.

(3) Thyroid stimulating hormone (TSH) and thyroid hormone-releasing hormone (TRH) mediate the thyroid hormone output in a classic negative feedback mechanism. TSH regulates (1) the synthesis of thyroglobulin (Tg), (2) the uptake and organization of iodine, (3) the iodication of Tg to form T4 and T3, (4) the storage of T3 & T4 in the gland as colloid, and (5) the hydrolysis of the stored Tg to release T4 and T3 into the circulation.

Follicle, the functional unit of thyroid gland, is separated from the interstitium by a complete basement membrane. Lobule is a group of 20-30 follicles, separated to each other by a thin fibrous connective tissue layer. Follicular cells contain T4, T3, and other low molecular weight such as cytokeratins, vimentin, and epithelial membrane antigen. Follicular cells with rich esinophilic cytoplasm are referred to as oncocytes, oxyphil cell, Askanazy cells or Hurthle cells. C cells or parafollicular cells are most abundant in a zone at the junction of the upper and middle thirds of the lateral lobes. They secrete calcitonin and other peptides (e.g. somatostatin, gastrin-releasing peptide, and thyrotropin-releasing hormone.)

Thyroid hormone biosynthesis requires 0.100 mg to 0.150 mg of inorganic iodide per day. The source of iodine is diet. Average, daily intake is from 0.3 to 0.7 mg per day (in the US). The total body pool is approximately 9 mg. About 8 mg located in colloid, which serves as a source of iodine when intake decreases. Circulating hormone is about 0.6 mg and free iodide in extracellular fluid is 0.15 mg. Most thyroid circulating hormone bound to a binding protein (TBG 80%, TTR15%, and albumin 5%). Only 0.3% of T4 and 0.3% of T3 is unbound.

The goal of peripheral thyroid hormone metabolism is to maintain the circulating and tissue T3 level, which appropriates for the thyroid hormone requirements. The unbound or free T3 crosses the cell membrane, by passive diffusion, through T3 receptors, which mediates the physiologic actions of thyroid hormone including growth, differentiation, calorigenesis, and TSH suppression.

Pathology

About 4% to 7% of the population has nodular thyroid disease. Approximately, 4% of these nodules are malignant and account for about 1% of all cancers. The incidence of thyroid nodules in female to male is 6.5% to 1.5%. However, the risk of being malignant thyroid nodules is twice as high in males as compare to females. Thyroid cancer develops most commonly between the ages 40 through 60.

Thyroid cancers are classified by their predominant histologic cell types, as follow: (1) well-differentiated malignant neoplasm (WDTC) accounts for 85% of thyroid cancers, including papillary, follicular, and Hurthle cell carcinomas, and (2) more aggressive variants include medullary carcinoma and anaplastic carcinoma (3) other tumors including lymphomas and metastatic tumors.

(1) Papillary Thyroid Carcinoma (PTC): is the most common, accounting for 75% to 80% of thyroid cancer and 80% to 90% of radiation induced thyroid carcinomas. Female to male ratio is 3 to 1. Peak incidence is in the 30s to 40s year of age, with prolonged course and rarely caused death (1% – 10%). The 10-year survival rate is from 84% to 90%. Tumors are usually composed of mixed papillary fronds or follicular component. According to the size and location of the tumors, there are three subclasses of papillary carcinomas (1) occult or less than 1.5 cm, (2) intrathyroidal, (3) extrathyroidal. The majority of papillary tumors are nonencapsulated, usually invade lymphatics and replace normal thyroid tissue. Grossly, these tumors often show central necrosis with fibrosis or hemorrhage; large tumors may have cystic degeneration and may resemble a benign thyroid cyst. Multicentricity develops in 75% of tumors, especially in patients with prior exposure to ionizing radiation. Papillary carcinomas have increased incidence in familial adenomatous polyposis syndromes such as Gardber’s and Cowden’s. Histologic findings of papillary tumors consist of columnar thyroidal epithelium set in papillary projection with well-formed fibrovascular cores or “psammoma bodies”. Nuclei are vesicular and house-glass or “Orphan Annie” appearance. Factors affect surgical treatment including extrathyroidal extension, vascular and adjacent structural invasion or lymph node metastasis. There is a high rate of local regional lymph nodes (50%) but low risk of hematogenous dissemination. Spires et al. at MD Anderson Cancer Center determined that the most important prognostic factors for papillary carcinoma of thyroid are (1) age, (2) sex, (3) histology of the cancer, and (4) presence of distant metastatic diseases.

(2) Follicular Thyroid Carcinoma (FTC) accounts for 5% of all thyroid cancers and 15% of primary epithelial malignant tumors of the thyroid, according to Segal et al. Peak incidence is in the fifth decade of life and female-to-male rate is 3:1. Follicular carcinoma tends to slow enlarging of non-tender nodules, hematogenous metastases to lung, bone and brain. Non-invasive tumors have a 10-year survival rate 86%, whereas invasive tumors have that of 44%. Grossly, follicular carcinomas are usually well encapsulated and grow in an expansive fashion. They undergo cystic degeneration, calcification, or hemorrhage. Microscopic finding is microfollicular pattern with vesicular nucleolus cells. The lumens of the acini are usually empty, without colloid. The most important feature of this type of cancer is the tendency to invade the thyroid capsule and blood vessels. The high-grade follicular carcinomas have marked hypercellularity and and difficult to differentiate with follicular adenoma. Therefore, multiple sections are required for identifying the capsular or vascular invasion. Follicular carcinoma is more aggressive than papillary carcinoma and is associated with a higher morbidity due to more rapid metastasis. In the study of Segal et al., the factors of (1) age (less than 40 years, (2) tumor size (<6 cm), (3) invasion of blood vessels (has significant effect the prognosis in the first 10 years) and (4) distant metastases (an important predictor for survival) show significant effects on the outcomes of follicular carcinomas.

(3) Hurthle (oxyphilic) cell Carcinoma is the most aggressive well-differentiated neoplasm and accounts for about 5% of WDTC or 2% to 3% of all thyroid cancers. There is high incidence of bilateral thyroid lobe involvement and long-term lethal potential for local recurrence and mortality if the tumors were treated less aggressively. Female to male ratio is 2 to 1. Hurthle cell carcinomas have poor prognosis with five-year survival rate in about 50% to 60%.

(4) Medullary Carcinoma (MTC) accounts for 5% to 10% of thyroid cancer. The tumor originates from calcitonin-producing parafollicular C-cell. Grossly, medullary tumors are gray to yellow, firm, well-circumscribed or invasive with bilateral multicentric involvement. Medullary carcinomas are classified as two groups:

(1) Sporadic (80%): have a poorer prognosis, usually unifocal, not associated with other endocrine tumors, occur in middle age to elderly patients, equal in both sexes; single nodule is common in sporadic form with clusters of cells and stromal amyloid in 85% to 90% cases,

(2) Family trait (20%): autosomal dominant inheritance, tumors associated with C-cell hyperplasia or the calcitonin-producing lesions; these tumors usually have early high calcitonin screening and better prognosis. The familial form of medullary cancers usually develop in the third decade of life with the female to male rate is 1.5 to 1. The familial medullary carcinomas are associated with other endocrine tumors such as:

(1) Sipple’s syndrome or multiple endocrine neoplasm type II (MEN IIa), including (a) medullary thyroid carcinoma or C-cell hyperplasia, (b) adrenal medullary carcinoma and (c) hyperparathyroidism.

(2) Wermer’s syndrome (MEN IIb), including (a) medullary thyroid carcinoma, (b) pheochromocytoma, (c) mucosal neuromas (of the tongue, lips, conjuctivae), ganglioneuromas of the intestines, characterized by special facial appearance, and marfanoid habitus.

Overall prognosis of MTC is poor due to early metastases to lymph nodes and distant metastases. The five-year survival rate is in the range of 60% to 70% and 10 year-survival rate is 40% to 50%. About 50% of medullary cancers have regional metastases to local lymph nodes at the time of diagnosis. Distant metastases include lung, liver, adrenal glands, and bones (osteoblastic, opposed to other cancers, e.g. prostate cancer, osteolysis).

(5) Anaplastic Thyroid Carcinoma (ATC) or undifferentiated carcinoma accounts for 3% of all thyroid cancers, more common in elderly patients usually in their seventh decade. Females are more affected than males. Tumors have higher incidence in patients with pre-existing multinodular goiter (30%). The anaplastic thyroid cancer is the most aggressive thyroid cancer, is unencapsulated, and is associated with extended invasion outside the gland. Grossly, the neoplasm has fleshy, tan-white appearance, with hemorrhagic and necrotic areas. Histological cells with spindle or giant-cell variants. Patients with the anaplastic thyroid carcinomas have poor prognosis. Patients usually die within several months, dues to airway obstruction, vascular invasion, distant metastases to lung and bone and resistant to the therapy.

(6) Malignant Lymphoma accounts for 1% to 2% of thyroid cancers, increasing incidence in endemic goiter areas, most common in patients over 50 years of age. The female to male ratio is 3 to 1. It may develop from the pre-existing Hashimoto’s thyroiditis and present as a rapidly growing mass in history of multinodular goiter. Rapid enlarging tumors can result in tracheal or esophageal compression. Grossly, tumors are large, yellow-tan, and scaly with hemorrhagic and necrosis areas. The most common variant of thyroid lymphomas are small-cell noncleaved type (or poorly differentiated malignant lymphoma) and the large-cell noncleaved folicular cell-type. The cell types and stages are the critical factors in prognosis, e.g. small cell, Hogkin’s, and immunoblastic lymphomas have a favorable prognosis in early stage (stage I: 86% 5-year survival rate with lymphoma limited in the gland, 38% with lymph node involvement or invaded capsule, and rare with disseminated thyroid lymphoma).

(7) Metastatic Carcinoma found in 2% to 4% of patients who die of cancers. Metastatic thyroid carcinomas are most common from malignant melanoma, lung, kidney, breast, and colon cancer. Malignant cells metastasize by lymphatic or vascular deposits of tumor emboli. To identify the metastatic lesions is important because when they exist surgical excision is not beneficial.

Prognostic Factors

*Histology: the cell type is one of the most predominant prognostic factor and influences other risk factors.

*Age: at the time of diagnosis is a significant effected risk factor, e.g. well-differentiated thyroid carcinoma has a greater tendency to invade the surrounding structures in patients older than 40. Mortality rate increases significantly in patients older than 60.

*Sex: females are at a higher risk of developing thyroid nodules, however, males have a higher risk of thyroid cancer. Tumors are more aggressive and the prognoses are poorer in males than those in females.

*Size of primary lesions: the larger the size of the tumor the greater the risk of vascular invasion or metastatic spread. Tumors greater than 1.5 cm carry a higher risk of recurrence and mortality.

* Extracapsular or vascular invasion and metastatic disease are poor prognosis factors. Regional metastasis in papillary carcinoma correlates positively with the incidence of local recurrence. Well-differentiated thyroid cancer, which invades and paralyzes the recurrent laryngeal nerve requires a wider resection. Distant metastases are rare in papillary cancers, but more often seen in follicular tumors, and are associated with poorer prognosis.

*History of radiation is associated with higher risk of papillary carcinomas requiring more extensive resection to eradicate disease.

The Mayo clinic uses the “AGES” system incorporating age, grade, extracapsular tumor, and size. The Lahey clinic uses the “AMES” system incorporating age, metastasis, extracapsular, and size. 

Diagnosis

The most common diagnostic measures include needle biopsy or aspiration, thyroid blood study, radiology imaging. Needle biopsy, a superior diagnostic technique, which provides accurate cytologic finding with no morbidity, has become the first step in thyroid nodule workup.

1. History and physical examination: a thorough history and head and neck examination should be the first evaluation of a thyroid mass. A malignant thyroid nodule usually presents as a painless mass. Other symptoms such as pain, hoarseness, dysphagia, dyspnea, stridor, hemoptysis, and rapid enlargement of the mass may occur with thyroid carcinomas but are not necessarily to be the signs of malignancy. A history of irradiation, especially in childhood, is an important risk for papillary carcinoma. External low dose irradiation is the treatment for some diseases, e.g. acne, tonsillar hypertrophy, enlarged thymus, cervical adenitis, sinusitis and malignant disease. Previous thyroid diseases such as goiter, Hashimoto’s disease and Grave’s disease can be risk factors for thyroid cancer. Systemic disorder such as Gardner’s syndrome, Cowden’s disease, lymphoma, or other malignant diseases should be evaluated in relationship to thyroid nodules. Physical exam includes the full head and neck examination. A benign thyroid nodule is usually well-circumscribed, soft, non-tender, and movable free to surrounding tissue. A malignant tumor is harder, can be greater than 4 cm in diameter and may fixed to the surrounding and underlying tissues. Neck examination can reveal palpable metastatic cervical lymph nodes, especially in the anterior compartment (level III, IV, VI) and less common in level V. Chvostek’s sign is helpful but not specific for hypocalcium level because about 10% of the normal population can have false positive tests.

2. Needle biopsy:

(1) Core needle biopsy provides adequate tissue for diagnosis in 90% of cases. Biopsy is guided by palpation. It is significantly more difficult, more traumatic and has more complication than fine needle biopsy

(2) Fine needle aspiration (FNA) is more prefer because of less morbidity. Technique is performed on a palpable nodule or under ultrasonography guidance. Fine needle biopsy is an accurate diagnostic procedure in papillary, medullary, metastatic, anaplastic cancers, and malignant lymphomas. Differentiation between follicular and Hurthle cell neoplasms is based on capsular or vascular invasion. Ashcraft and Van Herle, in a comprehensive review compared the accuracy of fine needle aspiration and core biopsy, concluded that neither biopsy technique is superior, but fine needle aspiration has a lower yield of tissue and almost free of complication. In a recent report, fine needle aspiration has false negative rate of 0.3 to 10%, and a false positive rate of 0 to 2.5%. Therefore, a malignant specimen on fine needle aspiration is a strong indication for surgery; however, a negative result cannot rule out cancer. There are some limitations of fine needle aspiration to differentiate (1) adenomatoid nodule vs. follicular neoplasm, (2) papillary carcinoma with cystic change and benign cystic nodules, (3) large multinodular goiters and present malignancy, (4) Hashimoto’s thyroiditis vs. oxyphilic cell (Hurthle) neoplasm, (5) multinodular goiter vs. Hurthle cell neoplasm, (6) Hashimoto’s vs. malignant lymphoma, (7) malignant melanoma.

3. Blood test: thyroid function tests include (1) thyroxin or T4, (2) triiodothyronine or T3, and (3) thyroid stimulating hormone or TSH. Serum calcium and phosphorous levels may indicate hyperfunction of parathyroid gland adenoma, which may be associated with thyroid gland malignancy. Thyroglobulin (Tg) is usually measured as a baseline before and following up after surgery of well-differentiated thyroid carcinomas because it correlates with histologic types of tumors. Recurrent tumors are usually associated with high Tg level. Calcitonin is a useful test for diagnosis and screening in patients with medullary thyroid carcinoma and their family members; however, it is not a work up test. Antimicrosomal and anti-Tg antibody titer are unrealistic tests for screening or following up a thyroid cancer because of high cost and low-specificity.

4. Trial of suppression of TSH, which is usually indicated in FNA negative for malignant nodules, applies thyroid hormone to suppress thyroid nodules. Levothyroxin suppression trial has showed decreasing volumes of thyroid nodules by 50% in approximately 40% of patients. The target of suppression test is to maintain released TSH levels between 0.1 and 0.5 mIU/L per day. Failure of suppression therapy is an indication for further workup or surgery therapy of the nodules.

5. Imaging studies:

• Ultrasonography: is one of the most sensitive and effective tests for differentiation a thyroid and non-thyroid nodule in more than 80% of cases. It provides an accurate tri-dimensional location, follows up the nodular size, and indicates nodular location for the fine needle aspiration. US can detect the nodules as small as 2 to 3 mm and differentiate between solitary and multinodular diseases.

• Radioisotope Scanning: to evaluate uptake of radioactive iodine or technetium of thyroid nodules compared with the remainder of the thyroid gland. Scintilation scanning has some value for routine evaluation of solitary thyroid nodules because the majority of both benign and malignant thyroid nodules are hyporeactive compared to adjacent tissues. Scanning with 123-I is more accurate but of greater cost and increases radiation exposure to the thyroid gland. However, radionuclide scanning is useful in the subgroups of patients with hyperthyroidism and autonomously functioning thyroid nodules. It is necessary to detect the remaining thyroid tissue after surgical resection as well as for presence of metastatic disease.

• Magnetic resonance imaging (MRI): is very useful to detect residual, recurrent and metastatic cancers. T2 imaging is useful in differentiation between tumors and fibroses in operated neck tissue, and detection of muscle invasion. MRI also shows tracheal displacement and vascular relationship involved with large masses. Fat-saturation MRI can be used in suspected recurrent tumors, which are not identified by radioiodine scan.

• Chest x-ray is helpful in detecting tracheal deviation, airway narrowing, and existent lung and bone metastasis. Patterns of calcification on chest x-ray are useful in identifying the types of cancer: (1) rim or eggshell calcification suggests a benign lesion, (2) bilateral calcification in superolateral aspect of the thyroid gland indicates MTC and (3) extensive irregular calcification suggests a multinodular goiter.

• Pre-operative laryngoscopy evaluates vocal cord paralysis and should be documented in suspected carcinomas.

Staging of thyroid cancer

Staging is determined by physical exam, thyroid imaging, and endoscopic examination:

1. Primary tumor:

• TX: primary tumor cannot be assessed

• T0: no evidence of primary tumor

• T1: Tumor is limited to the thyroid and <1 cm

• T2: Tumor is limited to the thyroid and >1 cm but <4 cm

• T3: Tumor is limited to the thyroid and >4 cm

• T4: Tumor of any size extending beyond the thyroid capsule; T4a: solitary tumor, T4b: multifocal tumor

2. Regional Lymph Node Metastasis:

• NX: Regional lymph node cannot be assessed

• N0: No regional lymph node metastasis

• N1: Regional lymph node metastasis;

N1a: ipsilateral lymph node metastasis

N1b: bilateral, midline, or contralateral cervical or mediastinal lymph node metastasis

3. Distant Metastasis:

• MX: Distant metastasis cannot be assessed

• M0: No distant metastasis

• M1: Distant metastasis; specific metastatic sites (e.g. pulmonary (PUL), osseous (OSS), liver (HEP), brain (BRA), lymph nodes (LYM), etc)

Note: undifferentiated (anaplastic carcinoma) is considered by definition as stage IV tumors.

Clinical staging of papillary or follicular carcinoma:

• Patient under 45 years of age:

. Stage I: any T, any N, M0

. Stage II: any T, any N, M1

• Patient over 45 years of age:

. Stage I: T1, N0, M0

. Stage II: T2 or T3, N0, M0

. Stage III: T4, N0, M0, or any T, N1, M0

. Stage IV: any T, any N, M1

 

Clinical staging of medullary carcinoma:

• Stage I: T1, N0, M0

• Stage II: T2, T3, or T4, N0, M0

• Stage III: any T, N1, M0

• Stage IV: any T, any N, M1

Management

A. Well-differentiated Thyroid Carcinoma: (Papillary, Follicular, and Hurthle cell)

1. Surgery:

Tumor analysis should be done before the surgery regarding to the factors such as age, gender, extranodular invasion, distant metastasis, nodule size and involvement. A study at Memorial Sloan-Kettering Cancer Center from 1930 to 1980 identified female gender, multifocal primary tumor, and regional lymph node metastasis as favorable prognostic factors. On the contrary, age > 45, follicular histology, extrathyroidal extension, primary tumor >4 cm and presence of distant metastasis give worse prognoses.

All thyroid nodules should be approached as potential malignancies. Typically, total thyroidectomy is indicated for malignant lesions within one or the other lobe of the gland. Lobectomy is an option if frozen section (and subsequent permanent) histology returns a benign diagnosis.

According to Cannon, recurrent laryngeal nerve (RLN) is the key to thyroid operations. When the nerve cannot be found in the usual location, surgeons should dissect very carefully to identify the nerve near the superior pole of the thyroid gland. In the lateral aspect of the gland, the branches of the inferior thyroid artery and the parathyroid glands are dissected free of the thyroid globe, without interrupting their blood supply. Parathyroid autotransplantation is recommended when the glands or their blood supply are injured.

• Total thyroidectomy most commonly performed for WDTC. Total thyroidectomy allows for complete removal of primary tumor, reduced local recurrent rate to 26% (40% with lobectomy). Preparation for total thyroidectomy includes 131-I scanning, medication history, recurrent laryngeal nerve examination (pre-op documented recurrent laryngeal nerve function by Machida’s scope or direct laryngoscopy), and pre-op Tg level.

• Partial thyroidectomy (lobectomy and isthmusectomy): is the basic minimal operation for thyroid cancers (nodulectomy is contraindicated). The procedure allows for identification and preservation of the parathyroid glands with blood supply and the recurrent laryngeal nerve. Indications for the procedure include unifocal, intrathyroidal, and nonmetastatic papillary carcinomas less than 1.0 cm in diameter; patient has no previous exposure to radiation and contralateral lobe is clinical normal. A study from Memorial Sloan-Kettering Cancer Center concluded that low-risk patients undergoing lobectomy are likely do as well as with total thyroidectomy and with less morbidity.

• Near total thyroidectomy leaves a minimal amount of thyroid tissue and preservation of the recurrent laryngeal nerve and parathyroid gland with their blood supply. This is the treatment for micro-carcinomas if multifocality or local lymph node metastasis is present. Micro-carcinomas are usually associated with bilateral tumor focci. Postoperative radioiodine scanning and therapy are necessary. Falk and McCaffrey reported that there were no differences in survival rate between complete excision with resection of recurrent laryngeal nerve and near total thyroidectomy with preservation of the nerve.

• Role of neck dissection in conjunction with thyroidectomy for WDTC is a controversial topic. Several studies showed that pathological evaluation of elective neck dissection has not improved the survival rate in papillary carcinoma. No neck dissection is necessary for the N0 neck and there is wide agreement on this among head and neck surgeons. Coburn and Wanebo reviewed retrospectively 108 patients in their clinic and concluded that patients age> 45, cervical lymph node positive, and positive mediastinal nodes need more aggressive treatment including modified neck dissection (preserves the jugular vein, SCM muscle, and spinal accessory nerve). Invasive tumors are removed completely with preservation of involved organs (trachea and esophagus). Elective removal of lymph node is inadequate and should be avoid.

2. Adjuvant therapy:

• Post-op radioiodine (RAI): with appropriate dose, radiation therapy is safe in both children and adults. When patients have significant hypothyroidism (TSH>50 mU/L), 4 to 5 mCi of 131-I is given and the total body is scanned to look for residual thyroid tissue or metastasis. The scan and treatment are repeated until the scan is negative. Patient will receive follow up annually for several years. For the rest of life, patient’s TSH should be held in low normal range by maintaining T4 level in high normal range. According to Attie et al., RAI uptake scanning is an essential indication after a thyroidectomy to determine the completeness of the surgical procedure and to detect residual or metastatic disease. Wong et al. reported 131-I therapy prolonged lifespan even in disease-free patients after thyroidectomy.

• External beam radiation is useful in advanced locoregional WDTC whether superficial excision is complete or incomplete, if the tumor no longer picks up radioiodine, and in post-op adjuvant therapy for palliation of unresectable bone metastasis. The average dose is 50 Gy in 25 fractions over 5 weeks. Wu et al. reported that postoperative radiotherary is more effective in well-differentiated thyroid carcinomas than in poorly differentiated carcinomas.

B. Undifferentiated Carcinoma:

These tumors are usually unresectable. Tracheotomy is considered when airway is compressed. Diagnosis is made by FNA and usually by open biopsy for completed cell study. A combination treatment of surgery, radiation or chemotherapy may help to control the tumors.

• Chemotherapy: undifferentiated thyroid carcinoma is generally not chemotherapy-sensitive. The most effective agent is adriamycin (doxorubicin). The approved combination by FDA includes adriamycin and cisplatin with hyperfractionated radiotherapy and debulking surgery may be used.

• Radiation therapy: anaplastic cancer does not concentrate 131-I. The only radiation is external beam therapy. Without evidence of apparent metastasis at the time of initial treatment, the average survival rate for this tumor is only 6 months.

C. Medullary Thyroid Cancer:

Cervical metastasis at the time of diagnosis is observed in 50% of cases. Surgical resection includes the anterior compartment node dissection, which removes the lymphatics and adipose tissue from the hyoid bone to the sternal notch and laterally to the internal jugular vein. The lymph node groups removed are pre-tracheal, paratracheal, pre-cricoid, Delphian and perithyroidal nodes. With N(+) cervical lymph nodes, a selective lateral neck dissection of zones II, III, IV can be included.

Recurrent MTC is resistant to chemotherapy and radiation. Moley reported that chemotherapy cured 28% and controlled 69% of patients. At the MD Anderson hospital, radiation is used as an adjuvant therapy in patients with soft tissue invasion, multiple positive nodes and metastatic MTC. When diagnose early and treat appropriately, the expected 10-year survival rate of MTC is about 90%. The most effective treatment is primary total thyroidectomy. Indications include the following reasons: (1) the C-cells have diffuse and bilateral anatomic distribution resulting in multifocal and bilobular tumors, (2) in the sporadic form, 30% of patients have bilateral involvement, (3) in the family cases, bilateral involvement is 100%.

D. Hurthle (oxyphilic) Cell Carcinoma:

The treatment of choice is total thyroidectomy because the tumor is aggressive and relatively unresponsive to radiation therapy. Another option is partial thyroidectomy. If the frozen section is negative for malignancy, the procedure is adequate. If it comes back positive, complete thyroidectomy should be done within 2 weeks. Patients have N(+) cervical lymph nodes need a routine modified neck dissection. Post-op thyroid suppression is helpful because Hurthle cell tumors have TSH receptors. Postoperative radioactive iodine is not indicated because these tumors take up 131-I poorly.

Surgical complications

1. Nonmetabolic complications:

• Nerve injury: superior (SLN) and recurrent laryngeal nerves (RLN) are most commonly injured. The morbidity caused by nerve injury depends on the extent and nature of the damage. SLN normally courses medially to the superior thyroid artery. Teitelbaum et al. reported unilateral SLN injury in about 5% of thyroidectomies. SLN injury can be avoided by leaving superior pole vessels alone until the isthmus has been divided and the lobe has been substantially mobilized. Patients usually complain of unstable voice, difficulty with high pitch, dysphagia and aspiration due to decreased laryngeal sensation. Classic signs of bowing of the vocal cords, ipsilateral rotation of the posterior glottis and inferior displacement of the affected cord may be missed on indirect laryngoscopy. RLN injury can coexist with SLN paralysis one or both sides. The reasons for nerve injury are: (1) anatomic variations, (2) failure to recognize alteration in the normal course of the nerve because of pathologic conditions, (3) lack of meticulous hemostasis and fastidious anatomic dissection, and (4) suturing, stretching, and crushing injuries of the main trunk or branches. Unilateral RLN paralysis is not life threatening and is usually compensated by the shortening and movement of the opposite vocal cord across the midline and the fibrosis of the arytenoid muscle. Bilateral RLN injury can causes airway obstruction immediately or years later. The early symptoms are stridor and cyanosis shortly after extubation. These patients should be re-intubated.

• Hemorrhage: major post-op bleeding becomes apparent by excessive bloody discharge in the drain, swelling of the neck and cervical venous distension.

• Airway obstruction: is the major cause of morbidity and mortality in post-op thyroid surgery. Airway obstruction is caused by postoperative hematoma, laryngeal edema or bilateral vocal cord paralysis. Preceding symptoms are neck pain, swelling and stridor. Fiberoptic endoscopy can identify the extent of airway obstruction. Management includes IV steroids over 24-48 hours, if there is no bilateral VC injury.

• Chyle leak is a rare complication of neck dissection and usually occurs in patients with previous neck irradiation or surgery.

• Pneumothorax is a rare complication, caused by injury to the apical pleura. It requires immediate recognition and applies of positive pressure respiration to keep the lungs expanded, as well as prompt closure of the wound to prevent recurrence.

• Postoperative nausea and vomiting (PONV) is associated with complications of general anesthesia, gender (more common in women), and intense operative vagal stimulation (e.g. surgical handling of neck structures. Fujii et al. reported that the incidence of PONV has been shown as high as 60% to 65% in patients undergoing thyroidectomy without prophylactic antiemetics. PONV can be avoided by prophylaxis treatment with 5-HT3 antagonists (e.g.granisetron, ondansetron), droperidol, metoclopramide or other antiemetic agents.

2. Metabolic complications:

• Hypothyroidism: usually occur after a total or near total thyroidectomy, more common in Grave’s disease.

• Hypocalcemia is caused by an inadvertent parathyroidectomy, in about 5% of thyroidectomies. It can be avoided by meticulous dissection and autotransplantation of the parathyroid glands.

• Thyroid storm: is a life threatening complication in patients with hyperthyroidism, and is caused by a disordering of hemeostasis owing to acute decompensation of the cardiovascular system, CNS, GI tract, and hepato-renal system. This complication is usually associated with a systemic illness (e.g. infection) in the postsurgical stage. It should be differentiated from malignant hyperthermia. Therapy includes (1) reduce hormone synthesis and release from the thyroid gland, (2) antagonize peripheral action of circulating hormones, (3) provide supportive care and (4) define and treat any precipitating conditions.

MANAGEMENT OF INVASIVE THYROID CARCINOMA

 Introduction

Invasive thyroid carcinoma encompasses any malignant tissue that protrudes beyond the capsule of the gland. Although rare, extrathyroidal invasion is associated with a worse prognosis and increased risk of morbidity. Management remains controversial, with some authors advocating conservative treatment with preservation of midline structures and others, aggressive extensive en bloc resection. There are a number of prognostic factors to consider when evaluating thyroid nodules and thyroid cancer risk.

Prognostic Factors

In addition to the standard TNM system (table below), a number of systems have been developed to gauge risk-group classification. The factors that determine prognosis in patients with well-differentiated carcinomas of the thyroid have been well delineated and are based on age, sex, and findings at the time of surgery. Several prognostic schemes, represented by acronyms, have been established by different groups and are as follows: AMES (Lahey Clinic, Burlington, MA), GAMES (Memorial Sloan-Kettering Cancer Center, New York, NY), and AGES (Mayo Clinic, Rochester, MN). The letters stand for A – age, S – sex, E – extent of primary tumor, M – metastasis to distant sites, and G – histologic grade of the tumor.

Depending on variables present, patients can be categorized into one of three groups: high, intermediate, or low risk. The classifications focus on parameters that are well established in the literature as risk factors for a poorer prognosis. A parameter common to all scoring systems is age given that patients over 45 years of age have a worse outcome than their younger counterparts. Larger primary tumor size and extension and the presence of metastases increase a patient’s stage and affect 5-year survival. For papillary carcinoma the 5-year relative survival rates by stage are 100% for stages I and II, 95.8% for stage III, and 45.3% for stage IV.

For follicular carcinoma the 5-year relative survival rates are 100% for stages I and II, 79.4% for stage III, and 47.1% for stage IV(17).

Specific prognostic factors are extremely important and include:

•Histology: the cell type is one of the most predominant prognostic factors and influences other risk factors.

•Age: at the time of diagnosis is a significant effected risk factor, e.g. well-differentiated thyroid carcinoma has a greater tendency to invade the surrounding structures in patients older than 40. Mortality rate increases significantly in patients older than 60.

•Sex: females are at a higher risk of developing thyroid nodules; however, males have a higher risk of thyroid cancer. Tumors are more aggressive and the prognoses are poorer in males than those in females.

•Size of primary lesions: the larger the size of the tumor the greater the risk of vascular invasion or metastatic spread. Tumors greater than 1.5 cm carry a higher risk of recurrence and mortality.

• Extracapsular or vascular invasion and metastatic disease are poor prognosis factors. Regional metastasis in papillary carcinoma correlates positively with the incidence of local recurrence. Well-differentiated thyroid cancer, which invades and paralyzes the recurrent laryngeal nerve, requires a wider resection. Distant metastases are rare in papillary cancers, but more often seen in follicular tumors, and are associated with poorer prognosis.

•History of radiation is associated with higher risk of papillary carcinomas requiring more extensive resection to eradicate disease.

TNM staging for papillary and follicular carcinoma(17)
Primary tumor (T) TX Primary tumor cannot be assessed T0 No evidence of primary tumor T1 Tumor 2 cm or less in greatest diameter, limited to the thyroid T2 Tumor > 2 cm and < 4 cm in greatest diameter, limited to the thyroid T3 Tumor > 4 cm in greatest diameter and limited to the thyroid or any tumor with minimal extrathyroidal extension (eg, extension to sternothyroid muscle or perithyroidal soft tissues) T4a Tumor of any size extending outside the thyroid capsule to invade subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve T4b Tumor invading prevertebral fascia or encases carotid artery or mediastinal vessels Regional lymph nodes (N) NX Regional nodes cannot be assessed N0 No regional lymph node metastases

 

N1 Regional lymph node metastases N1a Metastasis to level VI (pretracheal, paratracheal, and prelaryngeal nodes) N1b Metastasis to unilateral, bilateral, or contralateral cervical or superior mediastinal lymph nodes Distant metastasis (M) MX Distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis Stage grouping (for papillary and follicular carcinoma) Under 45 years of age Stage I Any T Any N Any M Stage II Any T Any N M1 45 years of age and older Stage I T1 N0 M0  Stage II T2 N0 M0  Stage III T3 N0 M0  T1 N1a M0 T2 N1a M0  T3 N1a M0 Stage IVa T4a N0 M0  T4a N1a M0  T1 N1b M0  T2 N1b M0 T3 N1b M0 T4a N1b M0  Stage IVb T4b Any N M0  Stage IVc Any T Any N M1

 

 

Diagnosis

The most common diagnostic measures include needle biopsy or aspiration, thyroid blood studies, and radiology imaging. Needle biopsy, a superior diagnostic technique, which provides accurate cytologic finding with little to no morbidity, has become an incremental step in thyroid nodule workup.

History and physical examination: a thorough history should be obtained. Symptoms such as pain, hoarseness, dysphagia, dyspnea, stridor, hemoptysis, and rapid enlargement of the mass may occur with thyroid carcinomas, but are not necessarily to be the signs of malignancy. A history of irradiation, especially in childhood, is an important risk for papillary carcinoma. External low dose irradiation is the treatment for some diseases, e.g. acne, tonsillar hypertrophy, enlarged thymus, cervical adenitis, sinusitis and malignant disease. Previous thyroid diseases such as goiter, Hashimoto’s disease and Grave’s disease can be risk factors for thyroid cancer.

Physical exam includes the full head and neck examination. A benign thyroid nodule is usually well-circumscribed, soft, non-tender, and movable free to surrounding tissue. A malignant tumor is harder, can be greater than 4 cm in diameter and may be fixed to the surrounding and underlying tissues. Neck examination can reveal palpable metastatic cervical lymph nodes, especially in the anterior compartment (level III, IV, VI) and less common in level V. Pre-operative laryngoscopy evaluates for vocal cord paralysis and should be documented in all patients to determine the function of the recurrent laryngeal nerve and use for preoperative planning. If one cord is noted to be paralyzed, it is likely secondary to an invasive process until proven otherwise, and removal of the nerve can be planned in the future operative intervention.

Fine needle aspiration (FNA) is performed on a palpable nodule or under guidance using ultrasonography. Fine needle biopsy is an accurate diagnostic procedure in papillary, medullary, metastatic, anaplastic cancers, and malignant lymphomas. Differentiation between follicular and Hurthle cell neoplasms is based on capsular or vascular invasion. A malignant specimen on fine needle aspiration is a strong indication for surgery; however, a negative result cannot rule out cancer. There are some limitations of fine needle aspiration to differentiate (1) adenomatoid nodule vs. follicular neoplasm, (2) papillary carcinoma with cystic change and benign cystic nodules, (3) large multinodular goiters and present malignancy, (4) Hashimoto’s thyroiditis vs. oxyphilic cell (Hurthle) neoplasm, (5) multinodular goiter vs. Hurthle cell neoplasm, (6) Hashimoto’s vs. malignant lymphoma, (7) malignant melanoma.

Blood test: thyroid function tests include (1) thyroxin or T4, (2) triiodothyronine or T3, and (3) thyroid stimulating hormone or TSH. Serum calcium and phosphorous levels may indicate hyperfunction of parathyroid gland adenoma, which may be associated with thyroid gland malignancy. Thyroglobulin (Tg) is usually measured as a baseline before and following up after surgery of well-differentiated thyroid carcinomas because it correlates with histologic types of tumors. Recurrent tumors are usually associated with high Tg level. Calcitonin is a useful test for diagnosis and screening in patients with medullary thyroid carcinoma and their family members; however, it is not a work up test. Antimicrosomal and anti-Tg antibody titer are unrealistic tests for screening or following up a thyroid cancer because of high cost and low-specificity

Imaging studies:

• Ultrasonography: is one of the most sensitive and effective tests for differentiation a thyroid and a non-thyroid nodule in more than 80% of cases. It provides an accurate tri-dimensional location, follows up the nodular size, and indicates nodular location for the

fine needle aspiration. US can detect the nodules as small as 2 to 3 mm and differentiate between solitary and multinodular diseases. It is however not useful in detecting invasive disease. If one suspects invasion based on physical examination findings, such as fixed nodal disease or true vocal cord paralysis, then further imaging, such as CT or MRI is necessary. CT is useful in detecting tracheal invasion and evaluating for cervical metastasis. One drawback to this test for thyroid cancer is that it may delay postoperative radioactive iodine treatment.

• Magnetic resonance imaging (MRI): is very useful to detect residual, recurrent and metastatic cancers. T2 imaging is useful in differentiation between tumors and fibroses in an operated neck tissue, and detection of muscle invasion. MRI also shows tracheal displacement and vascular relationship involved with large masses. Fat-saturation MRI can be used in suspected recurrent tumors, which are not identified by radioiodine scan.

• Chest x-ray is helpful in detecting tracheal deviation, airway narrowing, and existent lung and bone metastasis. Patterns of calcification on chest x-ray are useful in identifying the types of cancer: (1) rim or eggshell calcification suggests a benign lesion, (2) bilateral calcification in superolateral aspect of the thyroid gland indicates MTC and (3) extensive irregular calcification suggests a multinodular goiter.

.

Classification, Pathology, and Biology

Well-differentiated thyroid carcinomas (WDTC) – Papillary, Follicular, and Hurthle cell.

Papillary, follicular, and Hurthle carcinomas are classified as well-differentiated malignancies. Papillary and follicular carcinomas are the two most common malignancies found in the thyroid gland and occur 60-70% and 10% of the time, respectively Hurthle cell makes up about 3% of thyroid malignancies. All three of these cancers arise from the thyroid hormone producing follicular cells, however, their pathogenesis is largely unknown (15). Unlike medullary carcinoma, they do not have a definite genetic inheritance pattern. Only a small number are thought to occur in rare familial syndromes (15). Recent research has lead to the identification of a few cancer-causing genes that may be responsible for the benign or malignant transformation of follicular cells. Specifically, RET proto-oncogene mutations have been implicated in papillary and medullary carcinoma but a definitive link has yet to be proven (14). Despite the uncertainty of these molecular events, certain clinical factors, such as exposure to radiation, increases the likelihood for developing thyroid cancer, especially papillary carcinoma. In areas with endemic goiter, in populations that are iodine deficient and therefore have high level of TSH stimulation, the incidence of follicular carcinoma is high. Although this relationship has been confirmed in the laboratory where follicular carcinoma can be induced by exposure to TSH after exposure to a mutagen, the exact mechanism for this is not known (16). This relationship has not been consistent with papillary or Hurthle cell carcinoma.

.Papillary and follicular carcinomas are more frequently found in women. The mean age of incidence of papillary carcinoma is 35, while follicular tends to occur at an older age than papillary, with a mean age of 50 years (6). Lymph node involvement is relatively common in papillary carcinoma, with lymphatic spread being the major route of metastasis. In contrast to papillary carcinoma, follicular carcinoma tends to metastasize via angioinvasion and hematogenous spread and has a higher frequency of distant metastasis. When nodes are involved in follicular cancer, however, outcome is usually poor. This probably relates to the fact that patients with lymph node involvement at the time of diagnosis are also likely to have significant local disease and visceral invasion (43). Bone is the most common site of distant metastasis, with lung coming in second.

One of the most controversial and confusing neoplasms of the thyroid gland is the Hurthle cell carcinoma (HCC). This WDTC comprises approximately 3% of thyroid malignancies (6). These cells are believed to be a derived from follicular cells and together form a variant of a follicular neoplasm (6). A Hurthle cell neoplasm is defined as an encapsulated group of follicular cells with at least a 75% Hurthle cell component. Like follicular carcinoma, HCC requires histologic proof of vascular and capsular invasion to distinguish it from an adenoma. This makes diagnosis with either FNA or frozen section almost impossible, requiring permanent sections. Although classified as a WDTC carcinoma, HCC is more aggressive than follicular carcinoma. It also has a greater propensity for malignant transformation to anaplastic carcinoma than any other WDTC.

Medullary Thyroid Carcinoma (MTC)

Medullary thyroid carcinoma accounts for approximately 10% of all thyroid cancers and has an incidence of approximately 1000 new cases, in the United States, each year (1). It arises from the parafollicular cells or C-cells of the thyroid gland that differentiate from neural crest cells during embryologic development. Medullary thyroid cancer develops as either sporadic or familial. Overall, MTC tends to be a more aggressive cancer than the WDTCs. It usually spreads early by lymphatic dissemination to peritracheal and mediastinal lymph nodes has an over all incidence of lymph node metastases >50%.

Sporadic MTC accounts for approximately 70%- of all MTCs (5,29). The mean age at presentation is 50 years (41). This form of MTC tends to occur unilaterally and unifocally and usually presents as an enlarging thyroid nodule. It is slightly more aggressive than familial MTC, which composes the remaining 30% of medullary thyroid carcinomas. The most common clinical presentation of sporadic and inherited MTC is a mass in the neck

 

Anaplastic carcinoma (ATC)

Anaplastic carcinoma of the thyroid is a rare but highly lethal form of cancer with a median survival in most series of less than 8 months (22,23,25,27). It comprises 1%-10% of all thyroid tumors and up to 30% of thyroid malignancies in patients older than 70 years (26,28,45). ATC usually occurs in the elderly with a mean age of presentation of 60 years and has a slight female predominance (23). The most common clinical symptom is a rapidly enlarging mass and because of its aggressiveness, symptoms of invasion such as hoarseness, dysphagia, dyspnea, and superior vena cava syndrome are not uncommon.

Treatment Considerations

Wein and Weber (50) discussed a number of treatment considerations when evaluating thyroid cancer. These included:

When a follicular neoplasm’s obtained on FNA, 80% benign, 20% carcinoma. Of this 20%, up to 50% have the diagnosis of follicular variant of papillary carcinoma.

• For patients with follicular carcinoma the most important prognostic parameter is age, not sex. Patients 45 years of age or older at the time of diagnosis have a worse prognosis than their younger counterparts.

• Individuals with carcinomas greater than 5 cm fare worse, probably because of extracapsular spread.

• Patients with vascular invasion do worse than individuals with capsule invasion.

• Insular carcinoma is also considered to be a variant of follicular carcinoma that presents with more advanced-stage disease at diagnosis, a higher frequency of metastasis, and a decreased survival when compared with pure follicular carcinoma.

• Papillary carcinoma has a number of variants requiring special consideration.

  • ·        The diffuse sclerosing variant is a rare subtype that tends to present in women younger than 25 years of age. Tumor size is large at presentation (mean, 6.9 cm) with 100% of patients developing regional lymph node metastases. Despite these factors, prognosis seems to be favorable when aggressive care is rendered
  • ·        The tall cell variant, representing approximately 5% of papillary carcinomas, is also considered an aggressive subtype with a worse prognosis. Typical presentation is in the older patient with a large tumor, extrathyroidal extension, and nodal metastases.
  • ·        The follicular variant of papillary carcinoma, representing approximately 24% of cases, is more frequently multicentric but has clinical behavior similar to pure papillary carcinoma.
  • ·        Hürthle cell carcinomas, considered by some to be a variant of follicular carcinomas, represent only 3% of all thyroid tumors.
  • ·        Ipsilateral lymph node metastases are present in 25% of patients.
  • ·        In patients with metastases, only 38% of lesions demonstrated uptake of radioactive iodine (RAI)

Management

Invasive Carcinoma

The locally invasive presentation of well-differentiated thyroid carcinoma occurs in less than 5% of all cases. The most common pathology involved is papillary carcinoma. There is a male predominance with patients presenting at a higher mean age than those with noninvasive disease (31). Invasive thyroid carcinoma spreads by direct extension from the primary tumor or from extracapsular spread of paratracheal nodal metastasis. Tumor at the primary site has the capacity for invasion through the cricothyroid membrane or the thyroid cartilage anteriorly or may extend posteriorly to wrap around the thyroid cartilage and present in the region of the piriform sinus. Extracapsular spread from paratracheal nodes tends to invade laterally in the region of the tracheoesophageal groove .

The goals of treatment for invasive thyroid carcinoma include prevention of hemorrhage and airway obstruction, preservation of a functional upper aerodigestive tract, prevention of locoregional recurrence, and long-term survival. Frequently the mandate for removing all gross disease is at odds with function-sparing surgery. Several authors have advocated a conservative approach of shaving the tumor (24,31,32,33) off the tracheal wall, but other authors advocate more aggressive approaches to accomplish a complete removal of tumor (11,21). Few disagree that the goal in treating invasive thyroid carcinoma is to remove all macroscopic disease noted at the time of surgery. The controversy lies in the degree of resection required to accomplish this result. For individuals with limited tracheal deficits but gross intraluminal spread of tumor, window and sleeve resections are necessary. For larger defects, up to one third the circumference of the tracheal, use of sternocleidomastoid and pectoralis major myoperiosteal flaps over T-tubes has been described (12). For larger defects, tracheal resection with re-anastomosis with release procedures while preserving at least one recurrent laryngeal nerve has been described with favorable results (19). McCaffrey et al (31) retrospectively compared three groups of patients undergoing surgery for thyroid carcinoma with limited tracheal invasion. These groups included individuals undergoing complete surgical excision (group I), shave resection with the potential for microscopic residual disease (group II), and incomplete resection with macroscopic residual disease remaining (group III). The overall 5-year survival was 79%. No significant difference was noted in survival between groups I and II, whereas survival in group III was the lowest. The authors concluded that for selected patients shave resection is a viable option that allows preservation of upper aerodigestive tract anatomy without compromising survival. The importance of postoperative RAI therapy and possible external beam radiation were also stressed.

Esophageal invasion, when present, tends to invade only the outer muscular layers of the esophagus. Because achieving wide tumor-free margins is less of an issue with thyroid carcinoma than with squamous cell carcinoma, limited resection without intraluminal entry is possible. When limited intraluminal invasion is encountered, primary closure of the defect after resection is an option when closure does not predispose to stricture formation. When extensive resections of the esophagus are required, options for reconstruction with pedicled and free tissue transfer parallel those described in the literature for the treatment of squamous cell carcinoma.

When a patient presents for thyroidectomy and the preoperative examination indicates paralysis of the recurrent laryngeal nerve, attempts to save the nerve at the time of surgery should not be pursued. Primary thyroplasty may be considered in this scenario. When the recurrent laryngeal nerve is noted to be functional preoperatively, attempts should be made to preserve the nerve if possible. Falk and McCaffrey (10) retrospectively compared patients who had a functional recurrent laryngeal nerve sacrificed at the time of thyroidectomy with those with nerve preservation and noted that complete resection of tumor and nerve sacrifice offered no survival benefit over potentially incomplete resection of tumor and nerve preservation.

Laryngeal invasion requires the surgeon to be aware of the various options in conservation laryngeal surgery if the goal of avoiding total laryngectomy is possible. Vertical partial laryngectomy may be appropriate for patients with unilateral disease, whereas a supracricoid partial laryngectomy may be considered for extensive anterior invasion (13). The indications for total laryngectomy include extensive laryngeal spread beyond the scope of organ-preservation surgery and involvement of more than one third of the cricoid ring.

In a recent article by Segal et al (43) they performed a retrospective review of 1200 pts with diagnosis of well-differentiated thyroid carcinoma. 49 pts (5%) showed involvement of an adjacent structure (larynx, trachea, esophagus) – 30 female, 19 male. The type of surgery, radiation treatment radioiodine treatment, and patient demographics were evaluated. Most

common pathologic finding was papillary carcinoma (43 pts, 88%). Follicular carcinoma, including Hurthle cell carcinoma was noted in 6 pts (12%). Anaplastic tumors were excluded. All patients underwent total thyroidectomy and central neck dissection. Eighteen also had functional neck dissection (37%). For extrathyroidal involvement, two main approaches were used – radical surgery to excise all microscopic disease, with or without adjuvant therapy (n=16) and surgery for macroscopic disease only, followed by iodine and radiation treatment for microscopic residual disease (n=33). Overall 5 year survival for invasive carcinoma was 78%, compared to 93% of noninvasive disease. The only statistically significant factor was large tumor size. They concluded that conservative procedures followed by radioiodide treatment were associated with similar survival rates as aggressive techniques, with less perioperative mortality and lower overall mortality.

There is little consensus regarding surgical management of invasive, well-differentiated thyroid carcinoma. The conservative school recommends preservation of the midline structures by shaving carcinoma from the larynx, trachea, and esophagus, which potentially leaves behind microscopic disease requiring radioiodine and radiation treatment. (7) The aggressive school recommends extensive en bloc resection of the tumor, including partial or total laryngectomy, pharyngectomy, or tracheal resection, as necessary, to obtain clear margins.

Undifferentiated Anaplastic Carcinoma

These tumors are usually unresectable. Tracheotomy is considered when airway is compressed. Diagnosis is made by FNA and usually by open biopsy for completed cell study. A combination treatment of surgery, radiation or chemotherapy may help to control the tumors.

Medullary Thyroid Cancer

Cervical metastasis at the time of diagnosis is observed in 50% of cases. Surgical resection includes the anterior compartment node dissection, which removes the lymphatics and adipose tissue from the hyoid bone to the sternal notch and laterally to the internal jugular vein. The lymph node groups removed are pre-tracheal, paratracheal, pre-cricoid, Delphian and perithyroidal nodes. With N(+) cervical lymph nodes, a selective lateral neck dissection of zones II, III, IV can be included.

Adjuvant therapy:

Post-op radioiodine (RAI): with appropriate dose, radiation therapy is safe in both children and adults. When patients have significant hypothyroidism (TSH>50 mU/L), 4 to 5 mCi of 131-I is given and the total body is scanned to look for residual thyroid tissue or metastasis. The scan and treatment are repeated until the scan is negative. Patient will receive follow up annually for several years. For the rest of life, patient’s TSH should be held in low normal range by maintaining T4 level in high normal range. According to Attie et al (2), RAI uptake scanning is an essential indication after a thyroidectomy to determine the completeness of the surgical procedure and to detect residual or metastatic disease.

Another controversial complementary treatment is external beam radiation. Some earlier reports recommend the use of external beam radiotherapy in all cases of aggressive disease because it improves local disease control, (20) even though there is no proof that it changes the survival rate. By contrast, others found no improvement in either local control or disease-free survival.(3,42) External beam radiation is thought to be useful in advanced locoregional WDTC whether superficial excision is complete or incomplete, if the tumor no longer picks up radioiodine, and in post-op adjuvant therapy for palliation of unresectable bone metastasis.

Surgical complications

Surgical complications can include injuries to the superior laryngeal nerve or recurrent laryngeal nerve, hemorrhage, airway obstruction, pneumothorax, chyle leak, hypothyroidism and hypocalcemia.

1. Nonmetabolic complications:

• Nerve injury: superior (SLN) and recurrent laryngeal nerves (RLN) are most commonly injured. The morbidity caused by nerve injury depends on the extent and nature of the damage. SLN normally courses medially to the superior thyroid artery. Teitelbaum et al.(48) reported unilateral SLN injury in about 5% of thyroidectomies. SLN injury can be avoided by leaving superior pole vessels alone until the isthmus has been divided and the lobe has been substantially mobilized. Patients usually complain of unstable voice, difficulty with high pitch, dysphagia and aspiration due to decreased laryngeal sensation. Classic signs of bowing of the vocal cords, ipsilateral rotation of the posterior glottis and inferior displacement of the affected cord may be missed on indirect laryngoscopy. RLN injury can coexist with SLN paralysis one or both sides. The reasons for nerve injury are: (1) anatomic variations, (2) failure to recognize alteration in the normal course of the nerve because of pathologic conditions, (3) lack of meticulous hemostasis and fastidious anatomic dissection, and (4) suturing, stretching, and crushing injuries of the main trunk or branches. Unilateral RLN paralysis is not life threatening and is usually compensated by the shortening and movement of the opposite vocal cord across the midline and the fibrosis of the arytenoid muscle. Bilateral RLN injury can causes airway obstruction immediately or years later. The early symptoms are stridor and cyanosis shortly after extubation. These patients should be re-intubated, then trached.

• Hemorrhage: major post-op bleeding becomes apparent by excessive bloody discharge in the drain, swelling of the neck and cervical venous distension.

• Airway obstruction: is the major cause of morbidity and mortality in post-op thyroid surgery. Airway obstruction is caused by postoperative hematoma, laryngeal edema or bilateral vocal cord paralysis. Preceding symptoms are neck pain, swelling and stridor. Fiberoptic endoscopy can identify the extent of airway obstruction. Management includes IV steroids over 24-48 hours, if there is no bilateral VC injury.

• Chyle leak is a rare complication of neck dissection and usually occurs in patients with previous neck irradiation or surgery.

• Pneumothorax is a rare complication, caused by injury to the apical pleura. It requires immediate recognition and applies of positive pressure respiration to keep the lungs expanded, as well as prompt closure of the wound to prevent recurrence.

2. Metabolic complications:

• Hypothyroidism: usually occur after a total or near total thyroidectomy, more common in Grave’s disease.

• Hypocalcemia is caused by an inadvertent parathyroidectomy, in about 5% of thyroidectomies. It can be avoided by meticulous dissection and autotransplantation of the parathyroid glands.

 

Postoperative treatment and follow up

Studies have demonstrated the usefulness of postoperative RAI in decreasing the local recurrence and mortality rates in patients with stage II and stage III well-differentiated thyroid carcinoma. For this reason, the routine use of postoperative RAI and thyroid hormone suppression has been advocated for patients with primary tumors larger than 1.5 cm (30,42). Radiation is also a postoperative consideration for tumors that do not respond to RAI and for management of distant metastasis.

Conclusion

The goal of management for invasive thyroid cancer is to remove all gross disease, especially in medullary carcinomas and Hurthle cell, which are less responsive to postoperative radioactive iodine administration. There is still a debate regarding optimal techniques and extent of surgical resection to perform when dealing with invasive disease. There are a number of techniques which can be performed to complete dissection, however minimally a total thyroidectomy and central neck dissection should be performed for invasive disease. It is also important to remember that the type of cancer and risk grouping can affect both prognosis and influence treatment decisions.

RECONSTRUCTION OF TONGUE BASE DEFECTS

Introduction

The oropharynx is comprised of four distinct sites 1) soft palate, 2) palatine tonsil/tonsillar fossa, 3) posterior pharyngeal wall, and 4) the base of tongue. The oropharynx is anotomically contiguous with the oral cavity, nasopharynx and hypopharynx. It is a complex anatomical and physiological site that is necessary for degluttation, speech, respiration, and immunological defense. These sites are prone to squamous cell carcinoma in individuals who have a history of extensive tobacco or alcohol use. Squamous cell cancer of the tongue base is one of the most challenging tumors to manage.

Anatomy

Oropharyngeal embryology

The oropharynx is derived from endoderm. Until the end of the third week, the endoodermally derived oropharynx is separated from the ectodermally derived nasal cavities by the buccopharyngeal membrane. By the fourth week, the pharyngeal pouches, grooves, arches, and membranes develop. The epithelial lining of the anterior tongue is derived from the first pharyngeal arch. The third arch is responsible for the posterior tongue. The third and fourth arch help form the hypopharyngeal eminence, which gives rise to the epiglottis. The anterior tongue is innervated by the nerve of the first arch, trigeminal, while the posterior tongue is innervated by the third arch nerve, glossopharyngeal. The secondary palate becomes recognizable in the ninth week, after the fusion of the maxillary processes. It is separated from the primary palate by the incisive foramen, and forms the posterior hard palate and the soft palate. The tonsillar fossa, palatine tonsils, and lingual tonsils form from the endoderm of the second pharyngeal pouch.

Surgical anatomy

The superior limit of the oropharynx is the superior surface of the soft palate, and the inferior limit is the superior surface of the hyoid bone. The anterior border is the soft palate and uvula, palatoglossal arch, and the V-shape circumvillate papillae of the tongue base. The vallecullae are the transition point from the tongue base to the epiglottis. They are paired grooves that are bouded by the lateral glossoepiglottic folds lateraly, and separated in the midline by the median glossoepiglottic fold. The posteriorly and lateral boundaries are the pharyngeal walls. Waldeyer’s ring, an area of lymphoid tissue, includes the palatine tonsils, adenoid pad, and lingual tonsil, which surround the oropharyngeal opening.

The soft palate separates the nasal cavity from the remaining aerodigestive tract during swallowing and speech. The junction of the hard and soft palate marks the end of the oral cavity, and the beginning of the oropharynx. The palatine aponeurosis is integral in the function of the soft palate. The aponeurosis is an extension of the periosteum of the hard palate, and the tensor veli palatini and levator veli palatini insert onto it. The tensor veli palatini is innervated by the mandibular nerve (CN V), and is responsible for elevating the soft palate, as well as, opening the eustachian tube. The levator veli palatini is innervated by the pharyngeal plexus (CN IX and X). The uvula is the midline structure that touches the base of tongue at rest.

The tonsillar fossa and palatine tonsils are paired structures that comprise the majority of the lateral pharyngeal wall. The tonsillar fossa is bound anteriorly by the palatoglossal arch and posteriorly by the palatopharygeal arch. The blood supply to the palatine tonsils include the tonsilar branch of the facial artery, ascending pharyngeal, the dorsal lingual, the descending palatine and branches from the internal maxillary arteries. Posterior to the tonsillar fossa is the superior pharyngeal constrictor, and the upper fibers of the middle constrictor. Posterolateral to the tonsillar fossa is the internal carotid, within the parapharyngeal space.

The posterior pharyngeal wall begins at the soft palate and extends down to the base of the epiglottis. The second vertebra is often palapated at the midline of the posterior pharynx. The posterior pharyngeal wall is a layered structure consisting of mucosa, submucosa, pharyngeal constrictor, pharyngobasilar fascia, and prevertebral fascia. The retropharyngeal space is a potential space between the pharyngobasilar fascia and the prevertebral fascia. The pharyngobasilar fascia acts as a natural barrier to tumor spread, once this fascia is violated, the tumor has a direct pathway to the vertebra and becomes unresectable.

The base of tongue is an important structure for swallowing and speech. The tongue base provides the primary force for movement of food from the oropharynx, around the epiglottis, and into the hypopharynx. The sulcus terminalis (a V-shaped furrow on the dorsal surface) divides the tongue into its oral and pharyngeal components. Its apex is marked by the foramen cecum. The tongue is a muscular organ covered by a thin layer of mucosa. There are two types of muscle which comprise the tongue—intrinsic and extrinsic. Intrinsic muscles have no outside attachments whereas extrinsic muscles have attachments to structures outside the tongue. Extrinsic tongue muscles include the genioglossus, styloglossus, chondroglossus and hyoglossus. Embryologically, the muscles on each side of the oral tongue develop separately and then fuse in the midline. This near-bloodless plane, the septum linguae, can be used for surgical access to the base of tongue. Blood supply to the tongue arises from the lingual arteries, which enter the tongue base medial to the hyoglossus muscle. An important branch from this artery is the sublingual arteries, as they form an anastomotic network which can supply blood to the contralateral half of the tongue. The hypoglossal nerve runs superficial to the facial and lingual arteries, and lateral to the hypoglossus muscle and genioglossus muscles. Tongue deviation, fasiculations, and tongue atrophy are signs of advanced tumor growth. Taste papillae, serous and mucus glands dot the tongue’s dorsal surface. Irregular lymphoid tissue lies at the tongue base and is referred to as the lingual tonsils.

The mandible, though not a structure of the oropharynx, is an important structure to understand when discussing surgical approaches to the oropharynx. It is a U-shaped bone composed of two external cortices and an internal marrow space. The temporomandibular joint serves as its pivot point. The mandible provides insertion for muscles and contributes the to functions of articulation, mastication, and deglutition. The vascular supply to the mandible comes from the inferior alveolar vessels, which run through the inferior alveolar canal, as well as from the periosteal, lingual and facial arteries. The inferior alveolar vessels anastamose across the mandibular symphysis. The majority of mandibular blood flow is from this medullary circulation. Less than 25% of cortical vascular supply is from the periosteal arterioles. Surgical exposure often disrupts supply from the lingual and facial vessels. Extensive periosteal stripping can lead to decreased arterial supply as well as venous stasis.

The vallecula is the area between the tongue base and the epiglottis. Irregular lymphoid tissue lies at the base of the tongue in this trough-shaped area. These “lingual tonsils” are part of the ring of lymphoid tissues that surrounds the oropharynx. The epiglottis is composed of a long spoon-like cartilage skeleton covered with mucosa. It serves as the posterior border of the vallecula and helps to direct food bolus around the larynx and into the piriform sinuses. Its cartilaginous makeup allows it to bend with elevation of the larynx and retrusion of the tongue base. As it bends posteriorly it covers the larynx and serves to direct food around it. After the tongue relaxes it quickly springs back into its upright position. A fibrous connective tissue structure runs between the hyoid bone anteriorly and the epiglottis posteriorly. This structure is called the hyoepiglottic ligament. It is an important barrier to the spread of cancer from the tongue base into the deep compartments of the larynx, preepiglottic and paraglottic spaces. It also serves as an important surgical plane for precise entry into the vallecula. It condenses medially to form the median glossoepiglottic fold. In advanced tongue base cancers, this tumor extends beyond this ligament into the pre-epiglottic space and into the laryngeal framework.

The oropharynx has a rich lymphatic drainage system. The majority of the lymphatic drainage is to levels I, II and III cervical lymph nodes. Midline structures such as the base of tongue, soft palate, and posterior pharyngeal wall drain to both sides of the neck. The tonsillar area and posterior pharyngeal wall also drain to the retropharyngeal nodes.

Incidence and Etiology

Oropharyngeal carcinoma occurs at a rate of 11.9/100,000 population anually with approximately 30,000 new cases per year. This is the fastest growing segment of Head and Neck cancer. There is a 3:1 male predominence, and among men African Americans have the highest rates, followed by whites, Vietnemese, and then native Hawiians. Tongue base tumors account for approximately half of all oropharyngeal tumors.

Etiologic factors include the same risk factors found for most upperaerodigestive tract carcinomas. Alcohol and tobacco each alone increase the risk of developing oropharyngeal carcinoma 1.2-9.0 times. When combined, the risk is not additive, but exponential.

Tongue base tumors

These tumors are among the most difficult to treat. These patients usually present at an advanced stage because these neoplasms may remain asymptomatic and hidden for many months. There is a male predominance, 70% are men, and they usually present in the sixth decade. Sore throat occurs in approximately 60%, and other symptoms include otalgia, dysphagia, “hot potato voice,” weight loss, or neck mass. More then 60% of these patients have at least one clinically positive node at presentation. Level II and III nodes are the predominant nodes, and there may be bilateral or contralateral nodal involvement at intial presentation. Five year survival is 40-60%, with nodal involvement this survival drops by half. Treatment of these tumors requires a multidisciplinary team consisting of oncologic surgeon, medical and radiation oncology, pathologists, and speech and swallowing specialists.

Surgical Resection

There are many approaches to resecting oropharyngeal masses. Some are simple, but many are complex due to the fact that some of the posterior and inferior oropharynx are hidden and difficult to expose adequately. Also, the close proximity of the mandible, vascular structures, nerves, parapharyngeal space, and narrow introitus make resection challenging. Surgical approaches attempt to gain wide exposure of the tumor and surrounding structures to obtain adequate tumor margins, and safely remove the tumor without damaging adjacent structures. Often, a neck dissection precedes the surgical approach to aid in identifying and protecting vital cranial nerves, and vascular structures.

Approaches to the oropharynx via the oral cavity are differentiated by how the mandible is involved. The transoral approach does not involve the mandible, whereas median labio-mandibulo glossotomy, midline mandibulotomy, lateral mandibulotomy, and mandibulectomy involve sectioning of the mandible.

Transoral excision can be used in select, small tumors of the base of tongue. The use of cold steel or laser may be used to obtain tumor free margins.

Anterior midline labiomandibuloglossotomy (Trotter’s procedure) can be used for tumors limited to the tongue base. It requires a lip splitting incision, median mandibulotomy, and bisecting the tongue through the septum linguae to reach the tongue base.

The mandibular swing procedure usually provides the best esposure for tongue base tumors. The lip is split similar to the Trotter’s procedure, but a lateral or paramedian mandibulotomy is performed. The mucosa and muscles of the floor of mouth are incised posteriorly up to the anterior tonsillar pillar. The lingual nerve and styloglossus muscle are encountered and transected to allow the mandible to swing laterally. This affords wide exposure to the oropharynx. If the tumor also invades the mandible, then mandibulectomy and soft tissue will need to be resected en bloc (commando procedure).

Surgical approaches to the oropharynx through the neck were initially developed subsequent to experience treating wounds caused by suicide attempts and slashings. Physicians realized that the pharynx and larynx could be reached through the neck with minimal injury to vital neurovascular structures. These procedures have been alternatively endorsed and discouraged over the past century. The concern for clear tumor margins with a relatively blind entry into the pharynx was the most serious criticism of these approaches. After techniques were developed that ensured precise entry into the pharynx, surgeons once again began to approach the oropharynx through the neck. Many authors now laud these techniques either alone or in combination with transoral approaches to treat lesions of the oropharynx. Several authors have shown that transcervical resection of oropharyngeal lesions when compared with traditional anterior approaches can result in similar survival and tumor-free margin data while significantly decreasing morbidity. Anterior pharyngotomy may also be used for selected, small tongue base tumors. The transhyoid approach requires transecting or removing the hyoid bone to gain access to the oropharynx, while the suprahyoid approach relfects the hyoid inferiorly to gain access to the oropharynx. The main drawbacks of this procedure are limited access, and the valleculae are entered blindly. Deeply invasive tonge base tumors may breach the hypoepiglottic ligament and extend into the laryngeal framework. These tumors may require a supraglottic or total laryngectomy in addition to tongue base resection.

Reconstruction of defects

The tongue base presents a challenge to the reconstructive surgeon because of its proximity to the larynx, and the risk of aspiration after its removal. Also, some cancers extend in to the anterior tongue and total glossectomy may need to be performed. The goals of tongue base reconstruction are 1) maintenance of the airway, 2) swallowing, and 3) articulation. The tongue base is integral in swallowing and respiration, but if a significant portion of the anterior tongue is removed during resection, then articulation becomes a problem as well. The ideal reconstruction provides protection from aspiration, dynamic capability for swallowing and speech, and a sensate tissue for more physiologic swallow.

Reconstructive ladder

The reconstructive ladder for the base of tongue begins with healing by secondary intention, primary closure, skin grafting, regional flaps, and microvascular free flaps. Small defects are those which are less than 30% of the tongue base volume, these can be closed by secondary intention, primary closure or skin grafting with little functional deficit. Defects larger than 30% must be closed by either a pedicled flap or free flap because primary closure or secondary intention lead to tongue tethering and functional deficits.

Regional flaps

The advantages of these flaps include single-stage reconstruction, well vascularized tissue, and relative ease of harvesting. Disadvantages are tip necrosis, limited superior reach, and bulky tissue. The pectoralis major flap is the workhorse flap, others include the sternocleidomastoid flap, latissimus dorsi, trapezius, and platysmal flaps. These flaps result in poorer function due to bulkiness, and insensate nature of the flap.

Microvascular flap

These flaps overcome many of the pitfalls of the regional flaps and have the ability to provide sensory and motor innervations. These flaps are technically more difficult to harvest and require a microvascular surgeon. The radial forearm flap is the workhorse, others include the lateral arm, lateral thigh, rectus abdominis, and latissimus dorsi. These flaps require diligence on the part of the surgeon, anesthesiologist, and perioperative nurses before, during, and after the microvascular anastomosis and inset. These flaps can offer great functional outcomes due to their ability to provide sensory as well as motor function.

Conclusion

The oropharynx is a complex anatomical region with limited access. Treating cancers in this region require a multidisciplinary team equipped with an oncologic surgeon, reconstructive surgeon, speech therapist, medical oncologist, radiation oncologist, oral surgeon, and dedicated nursing staff. The decision for surgical resection rests on size and stage of the cancer. Most of these cancers will be treated with a combination of radiation and chemotherapy, but for those select few, primary resection followed by post-operative radiation will give the patient equal survival chances. These patients will need reconstruction of there defect, and the most important determining factor should come down to quality of life for the patient. The method of reconstruction chosen must give the patient the best chance of reestablishing an oral diet and a stable airway without cannulation. This can be achieved by following the reconstructive ladder, and knowing the ones limitations as reconstructive surgeon.

TONSILLITIS, TONSILLECTOMY, AND ADENOIDECTOMY

       

History

Tonsillectomy and adenoidectomy has been performed by otolaryngologists, general surgeons, family practitioners and general practitioners. However, in the past 30 years the recognition for the need of standardization of surgical technique resulted in a shift in practice patterns so that it is almost exclusively performed by otolaryngologists. 

The history of tonsillectomy dates back over 2000 years when the first primitive scalpel was used by Celsus in approximately 50 A.D. to remove tonsil tissue. The earliest description of the procedure was by Paul of Aegina in 625. Not until the mid-eighteenth century did Caque of Rheims perform tonsillectomies on a regular basis. The early instruments that were used for tonsillectomy were actually first developed for removal of the uvula. Phillip Syng invented what would become the forerunner for the modern tonsillotome. The early version of adenoidectomy involved using a ring forceps through the nasal cavity to remove adenoid tissue by William Meyer in 1867. 

Anatomy 

The circular band of lymphoid tissue within the pharynx consisting of the adenoids, the palatine tonsils, and lingual tonsils is known as Waldeyer’s ring. The palatine tonsils are lymph tissue with prominent germinal centers. A capsule of connective tissue separates the tonsils from the lateral pharyngeal walls. The tonsil lies within a bed of three muscles that make up the tonsillar fossa. The anterior pillar is the palatoglossus muscle. The posterior pillar is the palatopharyngeus muscle. The superior constrictor muscle makes up the bed of the fossa. Medially, the tonsil crypts lay exposed to the oropharynx with specialized stratified squamous epithelium. The tonsil parenchyma can vary in its extent, sometimes extending into the nasopharynx causing nasal obstruction, and sometimes inferiorly causing extreme dysphagia. The tonsils are continuous with the lymphoid tissue in the base of the lingual tonsils. The point of attachment is known as the plica triangularis and must be transected during tonsillectomy.

 The tonsils are well vascularized with the majority of the blood supply arising from the tonsillar branch of the facial artery. The ascending pharyngeal, descending palatine, and the dorsal lingual branch of the lingual artery also contribute to the vasculature of the tonsil. The internal carotid artery lays just two centimeters posterolateral to the deep surface of the tonsil; however in 1% of the population, it is found just deep to the superior constrictor muscle. The nerve supply of the tonsils arise from the ninth cranial nerve and descending branches from the lesser palatine nerves. The tympanic branch of CN IX is thought to account for the referred ear pain in some cases of tonsillitis. The tonsils have no afferent lymphatic vessels. Their efferent lymph drainage is though the upper cervical nodes, especially to the jugulodigastric group. The base of the tonsil is separated from the underlying muscles by a dense collagenous hemi-capsule. The luminal surface of the tonsils is covered by deeply invaginated clefts of stratified squamous epithelium. These clefts are lined by specialized squamous epithelium which transports antigens by M type cells to be presented and processed by Antigen presenting cells. These are next transported to the extrafollicular area which has abundant T- lymphocytes which aid in the differentiation of B- lymphocytes. The lymphoid follicle is encased by the mantle zone where mature B- lymphocytes reside. At the core of the lymphoid follicle is the germinal center where B- lymphocytes produce antigen-specific immunoglobulin. 

The adenoids are midline folds of respiratory epithelium in the nasopharynx. The fossa of Rosenmueller is between the adenoid and the Eustachian tube. Gerlach’s tonsil is the tissue within the lip of the fossa of Rosenmueller which extends into the Eustachian tube. Passavant’s ridge is the most inferior aspect of the adenoid which may overlap the superior constrictor muscle. The ascending pharyngeal and sphenopalatine arteries provide blood supply to the adenoids.  

The surface of the adenoids differs from the tonsils in that the adenoids have deep folds and few crypts. The ciliated psuedostratifed columnar epithelium plays an important role in mucociliary clearance. After repeated or chronic infections, this layer thins resulting in stasis of secretions and impaired mucociliary clearance (3). The increase in antigen exposure from mucus stasis is thought to lead to an increased inflammatory response within the adenoid. 

Clinical Evaluation 

Tonsillar disease can be divided into recurrent acute tonsillitis, chronic tonsillitis, and obstructive tonsillar hyperplasia. 

                                      

Group A Beta hemolytic Streptococcus (GABHS) is the most common bacterial cause of acute tonsillitis, but only accounts for a small percentage of tonsillitis overall. It is most often initially evaluated by primary care physicians. Otolaryngology evaluation often takes place after resolution of the acute symptoms. In typical acute tonsillitis, symptoms of odynophagia or decreased oral intake progress to fever and tender cervical lymphadenopathy. Unfortunately, the history is often confusing when a patient is referred, as many of the supporting documents may be diagnosed as pharyngitis, URI, or viral syndrome. Certain key findings have been used to include patients in diagnosing the frequency of tonsillitis. These include fever greater than 38.5, positive GABHS culture, tender cervical lymphadenopathy > 2cm, and erythematous or exudative tonsils. It is important to differentiate viral from bacterial tonsillitis, because patients with viral tonsillitis do not require antibiotics. Patients with viral pharyngitis will often have a lower grade fever and less tonsillar exudates. A CBC will usually show a higher WBC in bacterial versus viral tonsillitis, as well as a higher shift in granulocytes versus lymphocytes. In about half of patients referred to an otolaryngologist, the actual number of infections does not correlate with the history given by patient or family. Therefore, in evaluating a patient with normal appearing tonsils and a subjective history supporting recurrent tonsillitis, serial examinations of the patient by the otolaryngologist to document the frequency and severity of infection are appropriate. Recurrent acute tonsillitis is documented as 4-7 episodes of acute tonsillitis in one year, five episodes per year for 2 years, or three episodes per year in 3 consecutive years. These numbers are not required to proceed with surgery, however. The severity of infections and associated complications, as well as lost productivity or school absences must also be considered. 

The differential diagnosis of exudative tonsillitis includes mononucleosis, scarlet fever, diphtheria, tularemia, toxoplasmosis, and malignancy (lymphoma, leukemia, and carcinoma). 

Infectious Mononucleosis is caused by the Epstein-Barr Virus (EBV). It causes an exudative, almost necrotic tonsillitis and impressive cervical lymphadenopathy and sometimes hepatosplenomegaly. Heterophile antibodies (monospot) help confirm the diagnosis, but may remain negative early in the disease. Titers of IgM and IgG are most specific. Treatment is usually supportive. In cases in which adenotonsillitis is so severe that airway symptoms emerge, steroid and antibiotic therapy may be necessary. Ampicillin and Amoxicillin have been associated with a rash in 90% of EBV patients and should be avoided. 

The symptoms of scarlet fever are similar to those of pharyngitis. The sandpaper rash begins over the upper trunk and spares the palms and soles. The tongue may have a white coat through which red papillae project (strawberry tongue). Primary infection by Corynebacterium diptheriae is most often tonsillopharyngeal. It begins as only mild erythema or gray spotting, but progresses to for a confluent darker gray psuedomembrane often extending beyond the tonsil onto the pharyngeal walls. Once definitive confirmation is made, the diphtheria antitoxin should be administered immediately. Neisseria gonorrhea and acute HIV can also be causes of non-exudative pharyngitis. 

Complications of GABHS pharyngitis include cervical adenitis, neck abscesses, peritonsillar abscess, intratonsillar abscess, and internal jugular bacterial thombophlebitis (Lemierre’s syndrome), and post streptococcal Glomerulonephritis. 

Post streptococcal glomerulonephritis is usually seen in 2 to 6 year olds with pharyngitis during the winter months. Joint pain and oliguric renal failure develop 10 days after the pharyngitis. Most patients have circulating antibodies against streptococcal enzymes such as antistreptolysin O (ASO). Treatment focuses on eliminating the streptococcal infection with antibiotics and providing supportive therapy or diuretics until the glomerular inflammation resolves. The prognosis is excellent in children, whereas adults are more prone to permanent renal damage. 

The Adenoids and Airway Obstruction 

                                               

The triad of hyponasality, snoring, and open mouth breathing normally indicates enlarged obstructing adenoids. Patients being evaluated for obstructive airway symptoms will have varying degrees of snoring with apneic episodes and choking or gasping episodes. The sleep pattern is often disrupted with frequent awakenings and restless sleep. Associated findings may include daytime hypersomnolence, nocturnal enuresis, and behavioral disturbances. The most seriously affected patients may present with heart failure and failure to thrive. In cases in which the history is questioned, nocturnal videotapes or audiotapes of the child sleeping may be helpful to both the parents and the physician. 

                          

Sleep disordered breathing in children is usually caused by enlarged tonsils and/or adenoids. A standardized grading classification of the tonsils has been adopted based on the ratio of the tonsil size in relation to the oropharynx as measured between the anterior pillars:

GRADE                     Percent Obstruction

0                                 0

1                                 <25%

2                                 25-50%

3                                 50-75%

4                                 >75% 

The gold standard for diagnosis of obstructive sleep apnea is the polysomnography (PSG). In adults, the test is imperative in the diagnosis and documentation of OSA. Obstructive Sleep Apnea is diagnosed as an RDI >5, SpO2 <90%. Upper airway resistance syndrome is diagnosed as a RDI <5, and SpO2 >90%, and primary snoring when RDI <1 and SpO2 >90%. 

In children, an adequate and convincing history in combination with physical evidence of adenotonsillar hypertrophy is relied upon in lieu of a sleep study. The dilemma concerning PSG is that the current economic environment makes it difficult to obtain a PSG in every case. For a child in whom the diagnosis is unclear or who has an unusual risk for surgery, PSG should be performed. 

Medical therapy 

Recent recommendations by the Texas Children’s Health Plans recommend confirming streptococcal pharyngitis before beginning antibiotics. This can be done by a rapid Strep test and/or a throat culture. If strong suspicion of Strep is present, a negative Strep test should be confirmed with a throat culture. If the test is negative, treatment should be symptomatically with NSAIDS/Acetaminophen, and fluids. Antibiotics, if given, should be discontinued if results are negative. If the Strep test or culture is positive, then the child should be treated with the antibiotic of choice. 

GABHS is exquisitely sensitive to penicillin. Traditionally, a 10 day regimen with oral penicillin or injectable penicillin was most commonly used. Cephalosporins first became available in the 1970’s and have demonstrated a greater eradication rate of Streptococcus. Co-colonizing beta lactamase producing organisms (BLPO) that are most frequently cited as co-pathogens are Staphylococcus aureus, M. catarrhalis, H. influenzae, and anaerobes. In these patients, antibiotics with high potency against GABHS and that are beta lactamase stable, such as Augmentin, clindamycin, or cefdinir are superior to penicillin in eradication of GABHS. The macrolides are mainly used for patients with proven penicillin allergy. Erythromycin and clarithromycin should be used for 10 days as therapy. Azithromycin can be used for 5 days. The proper azithromycin dosing for GABHS tonsillopharyngitis is 12mg/kg/day (double dosing). Three day treatment with azithromycin has shown inferior eradication rates. 

Adenotonsillar size may be reduced enough to relive airway obstruction symptoms in 10-15% of children treated with a one month course of antibiotics against BLPO. Adenoid hyperplasia also may respond to a 6 to 8 week course of intranasal steroids. 

Indications for Surgery 

The indications for tonsillectomy have dramatically changed and are today more clearly defined. In adults, the most common indication is recurrent tonsillitis. The most common indication in children is obstructive sleep apnea. The only absolute indication for adenoidectomy is airway obstruction with secondary cardiopulmonary complications and failure to thrive. The relative indications include chronic nasal obstruction with rhinorrhea or recurrent sinusitis, recurrent otitis media with effusion, recurrent and chronic adenoiditis, speech and swallowing abnormalities, and suspected neoplasia. In children with chronic sinusitis, adenoidectomy is usually the first surgical intervention for two reasons: 1)approximately 67% will respond after adenoidectomy alone and 2) the high failure rate of pediatric sinus surgery. Children older than 4 experiencing recurrent otitis media have shown to benefit from adenoidectomy with the second set of tympanostomy tubes. Only limited benefit has been shown for adenoidectomy in conjunction with the first set of tubes. On the other hand, for chronic otitis media with effusion, initial tympanostomy tube placement without adenoidectomy is associated with a higher rate of repeat surgeries. 

Contraindications for adenoidectomy include cleft deformities and velopharyngeal insufficiency.

                                              

The absolute indications for tonsillectomy include severe dysphagia, failure to thrive, and cor pulmonale. Relative indications include recurrent acute tonsillitis, chronic tonsillitis, obstructive sleep apnea, peritonsillar abscess, suspected neoplasia and halitosis. Patients with a prior history of recurrent tonsillitis and prior peritonsillar abscess may be more likely to develop another peritonsillar abscess and are candidates for tonsillectomy. 

                                        

Recurrences of peritonsillar abscess are more common within the first year and in patients younger than 40. The overall recurrence rate for peritonsillar abscess is 10-15% (17). The need for tonsillectomy in adults with significant tonsil asymmetry is generally accepted, because of the need to exclude malignancy. In children, tonsil asymmetry is usually secondary to benign lymphoid hyperplasia and the asymmetry is often an illusion created by a difference in the depth of the tonsillar fossa (8). Associated symptoms such as night sweats, persistent fevers, weight loss, or cervical nodes may be indicators of tonsillectomy with microscopic examination. 

Innovative Surgical Techniques

There is now a wide variety of safe and effective surgical techniques for tonsillectomy and adenoidectomy. Current discussions about the choice of surgical technique are centered on morbidity such as pain, return to normalcy, perioperative and postoperative hemorrhage, and operating room time. There are a number of devices that challenge the standard tonsillectomy, including the intracapsular partial tonsillectomy, the Harmonic scalpel tonsillectomy, Laser assisted tonsillectomy, and tonsillar ablation and coblation. Electrosurgery has provided improvements in surgical technique by decreasing operating time and improving hemostasis. However, until the development of nonflammable anesthetics, such as halothane in the 1950’s, the application for tonsillectomy and adenoidectomy was limited. Electrosurgery has proved itself to be equivalent or superior to the other methods of tonsillectomy. It is currently the most popular technique for tonsillectomy. When compared to cold dissection, there is no difference in postoperative hemorrhage rates, but electrosurgery increases pain. The reduction in operative time and intraoperative blood loss has made it the most commonly performed technique of tonsillectomy. 

                                          

Intracapsular power-assisted partial tonsillectomy utilizes a 45 degree microdebrider at 1500 rpm to remove the tonsil from medial to lateral under direct visualization. The dissection is stopped when the tonsil capsule is approached. The proponents of the microdebrider tonsillectomy claim that there is significantly less postoperative pain and a quicker return to normal diet (day 3). It appears to be as effective as standard tonsillectomy in relieving airway obstruction.By performing a medial to lateral microdebridement, the tonsil capsule is left intact as a biological dressing overlying the pharyngeal musculature. Also, the medial to lateral dissection is performed distal to the arborization of the tonsillar vessels thereby exposing only the smaller arterioles, which theoretically could decrease the risk of delayed hemorrhage. Tonsil regrowth may occur since a rim of tonsil tissue is left on the capsule, so chronic tonsillitis is currently considered a contraindication for the procedure. 

The harmonic scalpel uses ultrasonic technology to cut and coagulate tissues at lower temperatures than electrocautery. Rather than electrical current, the harmonic scalpel creates mechanical energy and heat by vibratory motion resulting in much less lateral heat displacement. The advantages include better visibility because of less smoke, and a smaller risk of stray energy shocks or burns. Several small studies show similar intra-operative blood loss and post-operative hemorrhage rates, but significant improvements in post operative pain and comfort, when compared to other techniques. Radiofrequency tonsil reduction procedures include tonsillar ablation and coblation. Tonsil ablation involves injecting an electrolyte solution into the target tissue and delivering direct radiofrequency energy with resultant tissue contracture and volume reduction. Tonsil coblation involves medial to lateral surface application of similar energy. The coblation procedure has proved to be superior to ablation for several reasons. The amount of tonsil reduction is very unpredictable with ablation, with resection rates ranging from 30-70% despite standardization of technique. Tonsil ablation causes a much higher rate of airway swelling and was abandoned early in comparison trials with coblation. Finally, the ablation procedure is limited to the treatment of airway obstruction. The tonsil coblation procedure’s claimed advantages include early elimination of pain, reduced pain medicine usage, and early resumption of normal diet. The coblation is now being used as a capsular dissector in place of the electrocautery in complete capsular tonsillectomy. The greatest limitation for use in adenotonsillectomy is that the current hand piece is inadequate in coagulating and suctioning the adenoid tissue. 

Adjuvant therapy 

The main areas of controversy regarding adjuvant therapies with adenotonsillectomy include perioperative injection of local anesthetics, postoperative use of antibiotics, intraoperative steroid use, and postoperative pain management. 

The most commonly used perioperative local anesthetic has been 0.25% bupivicaine with 1:100,000 epinephrine. The injection is typically into the tonsillar fossa pre or post tonsillectomy. The advantages include ease of dissection, less intraoperative bleeding, and early postoperative pain improvement. There have been a few serious side effects including early airway obstruction, cardiac dysrrhythmias, and seizures and cerebrovascular accidents. Studies investigating this adjuvant therapy have been too small to show a significant benefit and therefore are not recommended as standard of care. 

Perioperative use of antibiotics has traditionally been included in the treatment regimen of children undergoing adenotonsillectomy. When compared to saline for post operative treatment, patients who received oral ampicillin had significantly fewer episodes of fever, less offensive odor, improved oral intake, less pain, and fewer days to return to normal activity. Antibiotic choices should include an antibiotic that is active against oral flora, usually oral penicillin. There is still some controversy regarding the best type of antibiotic and duration of use given the increasing emergence of antibiotic resistant bacteria. Use of prophylactic antibiotics should be routinely used when performed on a patient with a cardiac abnormality. (Following American Heart Association guidelines)

Dexamethasone has been the most studied and most accepted intraoperative steroid among otolaryngologists. It is given at a dose of 0.15-1.0 mg/kg intraoperatively. A meta analysis by Steward showed that, when compared to control subjects, children given steroids were two times less likely to have an episode of emesis the first day after tonsillectomy and were more likely to advance to eating a soft diet. Other advantages include possibly reducing postoperative pulmonary distress, decreasing subglottic edema, and pain reduction. 

Inadequate control of pain after tonsillectomy may result in poor oral intake, sleep disturbances, behavioral changes, emesis, and hospital re-admission. Unfortunately the ideal analgesic is not available. Tylenol and Tylenol with codeine are the most commonly used post-operative pain medicines. The use of NSAIDS has shown similar postoperative pain control as opiates but without the CNS effects. However, the theoretic increased risk of hemorrhage after NSAID use makes them less attractive, and controversial in managing post-tonsillectomy pain. 

Complications 

The mortality rate for adenotonsillectomy is 1 in 16000 to 35000, mostly from anesthetic complications and hemorrhage. The incidence of postoperative hemorrhage is 0.1- 8.1%. Transfusion is required in 0.04% of bleeding patients and mortality occurs in 0.002%.

Anesthetic complications include fire, laryngospasm, kinking of the endotracheal tube, and iatrogenic premature extubation. In cases of a large airway leak, wet sponges with strings placed around the endotracheal tube and frequent suctioning of accumulated gases can prevent fire. Meticulous attention to the removal of all resected tissues and suctioning of the pyriform sinus help to reduce laryngospasm. 

         

Eustachian tube injury due to excessive lateral resection of adenoid tissue or secondary to burns can predispose the patient to COME or a patulous Eustachian tube. Excessive resection and scarring can lead to velopharyngeal insufficiency. VPI is usually transient, but clinically significant in 1 in 1500-3000. If VPI persists beyond 2 months, speech therapy is indicated. Surgical intervention with pharyngeal flaps or palatal pushback may be indicated for persistent VPI. 

Nasopharyngeal stenosis is a dreaded complication of Adenotonsillectomy. Fusion occurs between the soft palate, and lateral and posterior pharyngeal walls. Treatment is very difficult. Surgical options include pharyngeal or palatal flaps. 

Long standing upper airway obstruction provides the patient with a mild auto- PEEP. Some patients may experience a significant change in pressure across the alveoli after adenotonsillectomy, resulting in a transudation of fluid and pulmonary edema. Initial management includes reintubation and administration of PEEP and gentle diuresis.

Because of the nature of the surgical procedure, it is not unusual for patients to complain of neck discomfort. However, in patients who complain of limited neck range of motion, flexion and extension lateral neck views should be obtained to evaluate for atlantoaxial subluxation. Children with Down’s syndrome should all be screened as well. If identified pre-operatively, intraoperative neck immobilization is mandatory. In the postoperative period, neurosurgery should be immediately consulted and the neck should be immobilized. 

Indications for twenty-three hour inpatient monitoring include the following: 

  • Age younger than 3.
  • Those with obstructive sleep apnea or craniofacial syndromes involving the airway.
  • Systemic disorders which would put the patient at increased perioperative risk.
  • Poor socioeconomic situation or other situation which would limit the patient’s ability to return quickly to the hospital.
  • When the procedure is done for a peritonsillar abscess.
  • Those experiencing vomiting or hemorrhage. 

The most common causes for unanticipated inpatient stays are emesis, hemorrhage, airway obstruction, and pulmonary edema. Children younger than 3 years old should be observed overnight. 

Management of Postoperative Bleeding 

The best management of postoperative bleeding is prevention during surgical resection. It is thought that the cause of early and delayed bleeding is inadequately coagulated tonsil vessels that retract into the pharyngeal musculature to later remerge and bleed. Any amount of bright red blood coming from the mouth or nose should create the suspicion of a postoperative bleed. The subjective report of unwitnessed bleeding may not always be accurate, but it is safer to air on the side of caution and overestimate the reported bleed. Overnight observation and venous access is warranted. A CBC should be obtained to assess the degree of hemorrhage and also to establish a baseline level in case of further bleeding. Coagulation testing with proper hematology consultation for abnormal values should also be obtained. For the cooperative patient, gargling with ice water and afrin can help to reduce or stop bleeding in order for an adequate examination. If a small punctuate lesion is found, local injection with lidocaine with epinephrine and silver nitrate or bovie cautery can be performed. Patients who are uncooperative or bleeding heavily should be taken to the OR immediately. Careful intubation with the otolaryngologist at the bedside is mandatory. Any fresh clot should be removed and recauterized. Carotid angiographies should be performed when there is any suspicion of possible injury to the carotid artery.

SPECIAL SITUATIONS IN THE MANAGEMENT OF TONSIL AND ADENOID

Introduction 

Tonsillectomies and adenoidectomies are 2 of the most common surgical procedures performed. In 1996, there were 274,000 adenotonsillectomies (T&As), 144,000 tonsillectomies (without adenoidectomy), and 136 000 adenoidectomies (without tonsillectomies) performed in the United States. The surgical treatments to remove pharyngeal lymphoid tissue are often performed for symptoms of upper airway obstruction, recurrent infection, refractory tonsillar bleeding and possible malignancy. 

Anatomy 

The lateral palatine tonsils, adenoids and anterior portion of the lingual tonsils form the ring of lymphoid tissue in upper part of the pharynx called Waldeyer’s Ring. The palatine tonsils are an encapsulated body of lymphoid tissue covered with a cryptic surface lined with stratified squamous epithelium. The capsule is continuous with the pharyngobasilar fascia that is closely adherent to the tonsillar tissue but loosely associated with the three muscles of the tonsillar fossa. The fossa is composed of the palatoglossus (anterior pillar), superior constrictor (most of the tonsillar bed) and the palatopharyngeal muscle (posterior pillar). For the arterial blood supply for the tonsils, there are typically three arteries at the lower pole: the dorsal lingual artery anteriorly, the ascending palatine artery (a branch of the facial artery) posteriorly, and the tonsillar branch of the facial artery. At the upper pole of the tonsil the ascending pharyngeal artery enters posteriorly, and the lesser palatine artery enters on the anterior surface. The tonsillar branch of the facial artery is the largest. 

The nerve supply is the tonsillar branches of the glossopharyngeal nerve at the lower pole of the tonsil and through the descending branches of the lesser palatine nerves, which go through the pterygopalatine ganglion. The cause of referred otalgia with tonsillitis is through the tympanic branch of the glossopharyngeal nerve. 

Grading of tonsils and tonsil positions 

                                          

Visual inspection without tongue blade can be adequate for examining the tonsils in most cases but sometimes in children with prominent tongues, long soft palates or small oropharynx a tongue blade can be helpful. The size of the tonsils are usually measured based on the enlargement of the tonsils as they extend toward the midline. Brodksy, Moore, and Stanievich described an assessment scale for tonsillar hypertrophy.This scale often used for measurement is based on percent obstruction and can categorized by values ranging from 0 to 4+, or as a corresponding percentage based on the distance from the anterior pillars and the medial edge of the tonsils. 

Tonsil variation can also be encountered based on positioning of the tonsils and relative shape. The tonsils can be bi-lobed, have asymmetric enlargement when comparing the upper vs. the lower poles which can result in either hypopharynx or rarely nasopharynx obstruction. 

Peritonsillar Abscess 

                                              

Peritonsillar Abscess (PTA) can arise near the superior pole of the palatine tonsil, or from infection in the tonsillar fossa due to adjacent acute tonsillitis. Their is also some evidence that the infection can arise from obstruction of Weber glands near the superior pole of the tonsil. The exact incidence of PTA is estimated at 30 cases per 100,000 people per year in the United States. The controversies surrounding PTA include proper diagnosis, the best method of management, and indications for tonsillectomy, either urgent or elective. Management issues can be further complicated in pediatric patients who are too young to tolerate bedside drainage under local anesthesia. 

                                                         

Diagnosis is historically by physical exam but as new diagnostic techniques have become available, other imaging such as ultrasound (US) and computed tomography (CT) have been used. Studies using intra-oral US by Lyon et al. and Blavias et al. have shown good results with finding abscesses and treatment with needle aspiration in these patients have been shown to be more successful by ER physicians. However, CT scans remains the imaging of choice in uncooperative children unable to tolerate examination by intra-oral US. 

Management centers on either aspiration or incision and drainage (I&D) at the bedside with local anesthesia or under general anesthesia in the operating room with possible tonsillectomy (Quinsy Tonsillectomy). Other options include treatment with antibiotics alone or interval tonsillectomy after infection has resolved. The controversy of the best treatment from the selected above is what has caused so much debate surrounding treatment for PTAs. Johnson et al. performed at EBM review of the effectiveness of tonsillectomy on PTA and what is the best method for acute management. Their findings showed that I&D had a slightly higher success rate vs. needle aspiration (94% vs. 92%), with I&D being more painful, with the NNT was 48 patients for I&D. Thus, the authors concluded that needle aspiration was the better initial treatment and then I&D if aspiration failed. The use of steroids was also looked at by Ozbek et al. which showed IM steroids were beneficial for several outcomes of patients concurrently treated for PTA by either needle aspiration or I&D. Some of these outcomes listed were less post-op fever after 24h and quicker ability to swallow water than placebo group. 

Unilateral Tonsillar Enlargement 

                                      

Most often due to asymmetric tonsil position rather than a unilateral enlarged tonsil. The nature of the enlargement can be due to uncommon infections such as atypical mycobacteria, fungi and actinomycosis. Other etiologies such as neoplastic processes are also possible, especially lymphoma and for this reason “true” unilateral tonsil enlargement must be ruled-out by excisional biopsy of the tonsil. 

Clinical presentation can be slow and progressive, with voice changes and new-onset snoring. Diagnosis is by excisional biopsy and accompanying CT scans can be helpful for recognizing any extracapsular extension. For suspected neoplasm a preoperative consultation with a pediatric oncologist for concurrent bone marrow biopsy can also be helpful while the child is already under general anesthesia. 

Hemorrhagic Tonsillitis 

Seen infrequently, but can result from both acute and chronic tonsillitis. In chronic or recurrent acute tonsillitis, dilated blood vessels on the surface of the tonsil can rupture and bleed. The bleeding can also arise from the tonsillar parenchymal tissue, or from previously unrecognized bleeding disorders. Treatment is hemostasis of the bleeding or tonsillectomy if the patient is young and uncooperative with local control and the bleeding is recurrent. 

Lingual Tonsil 

                                    

The lingual tonsils are non-encapsulated lymphoid tissue and extend from the tongue base to the vallecula. Recurrent infection and laryngopharyngeal reflux are often causes for hyperplasia of this tissue may lead to respiratory problems and, rarely, OSA. Although the lymphoid tissue in Waldeyer’s ring tends to decrease with advancing age, the lingual tonsil may increase in size as a compensatory response to previous adenotonsillectomy. Clinical presentation of lingual tonsil hyperplasia can be heralded by sore throat, globus sensation, speech change, dysphagia, obstructive sleep apnea in adults and pediatric airway obstruction. Lingual tonsil enlargement is usually discovered incidentally during difficult intubations, often for non-ENT related surgical procedures. Surgical treatment is indicated when a patient is refractory to medical therapy. Surgical treatment can include direct laryngoscopy and removal of the tonsil tissue with CO2 laser, sharp dissection or bovie cautery. 

Down’s Syndrome 

Down’s syndrome most often results from trisomy of chromosome 21 (95%) with the other 3-4% of cases having an unbalanced translocation. The syndrome is can be characterized by: mental retardation, microbrachycephaly, flat occiput, short neck, oblique palpebral fissures, epicanthal folds, flat nasal dorsum, small low-set auricles, stenotic ear canals, prominent furrowed tongue & microdontia with fused teeth.

Predisposing factors for OSA are: midfacial hypoplasia; micrognathia; narrow nasopharynx; small oral cavity; macroglossia; relative tonsil and adenoid hyperplasia; increased secretions; hypotonia of the palatal, lingual, and pharyngeal muscles; laryngotracheal abnormalities; and obesity. There is an increased incidence of chronic rhinosinusitis and tonsillitis in children with Down syndrome. 

Tonsillectomy and adenoidectomy (T&A) may be required in children with Down syndrome for treatment of upper-airway obstruction, OSAS, recurrent or chronic tonsillitis, recurrent peritonsillar abscesses, dentofacial abnormalities, and, rarely, for malignant neoplasms, spontaneous tonsil hemorrhage, and refractory halitosis.

In a study by Goldstein et al. they looked at length of hospitalization and postoperative outcomes of children who had tonsillectomy with comparison of patients with and without Down’s syndrome. They concluded that the rate of postoperative respiratory complications is higher and the duration until adequate oral intake is resumed is longer in children with Down’s syndrome. They also recommend that children with Down syndrome be admitted to the hospital overnight after undergoing tonsillectomy and adenoidectomy. 

Cleft Palate 

                                          

Submucous cleft palate has an appearance of a bifid uvula, a midline lucency of the soft palate and notching of the hard palate. The palatal hypofunction that results from the associated muscular abnormalities is known to carry a risk of VPI should an adenoidectomy be performed. 

An occult submucous cleft is a less well-recognized anatomical anomaly. It too involves abnormality of the structure and function of the palatal musculature, but is not detectable on oral examination. On endoscopic examination of the nasopharynx, there is loss of the midline convexity of the superior surface of the soft palate with either flattening or a midline groove, consistent with the absence of musculus uvulae. This is sometimes known as the ‘seagull sign’. 

The presence of an irregular mass of residual adenoid tissue can lead to VPI if it prevents the soft palate from moving to close against the posterior pharyngeal wall and there is space for air to escape around the residual tissue. Careful visualization of the postnasal space during or after adenoidectomy should minimize this problem. The precise effect of any remaining tissue depends on the pre-existing pattern of velopharyngeal closure (coronal, circular or sagittal). 

Indications

Tonsillectomy – The current clinical indicators for tonsillectomy as recommended by the AAO-HNS in 2000 are: 

  • Patient with 3 or more infections per year despite adequate medical therapy.
  • Hypertrophy causing dental malocclusion or adversely affecting orofacial growth documented by orthodontist.
  • Hypertrophy causing upper airway obstruction, severe dysphagia, sleep disorders, or cardiopulmonary complications.
  • Peritonsillar abscess unresponsive to medical management and drainage documented by surgeon, unless surgery performed during acute stage.
  • Persistent foul taste or breath due to chronic tonsillitis not responsive to medical therapy.
  • Chronic or recurrent tonsillitis associated with the streptococcal carrier state and not
  • responding to beta-lactamase resistant antibiotics.
  • Unilateral tonsil hypertrophy presumed neoplastic.

 

Adenoidectomy – The current clinical indicators for adenoidectomy as recommended by the AAO-HNS in 2000 are: 

  • Four or more episodes of recurrent purulent rhinorrhea in prior 12 months in a child <12. One episode documented by intranasal examination or diagnostic imaging.
  • Persisting symptoms of adenoiditis after 2 courses of antibiotic therapy. One course of antibiotics should be with a beta-lactamase stable antibiotic for at least 2 weeks.
  • Sleep disturbance with nasal airway obstruction persisting for at least 3 months. d) Hyponasal or nasal speech
  • Otitis media with effusion >3 months or second set of tubes
  • Dental malocclusion or orofacial growth disturbance documented by orthodontist.
  • Cardiopulmonary complications including cor pulmonale, pulmonary hypertension, right ventricular hypertrophy associated with upper airway obstruction.
  • Otitis media with effusion over age 4. 

Contraindications 

As described in Bluestone’s Pediatric Otolaryngology, contraindications can be divided into 4 categories; velopharyngeal, hematologic, immunologic and infectious. 

  • Velopharyngeal insufficiency are usually a contraindication for adenoidectomy. These are for cleft palate patients and those with neuromuscular and neurological disorders.
  • Hematologic contraindications to tonsil or adenoid surgery are anemia or any disorder of hemostasis. Surgical intervention in this population can still be undertaken provided the proper work-up and pre- and post-operative management is in place for this patient group.
  • Respiratory allergy untreated can represent a relative contraindication for some physicians. A trial of anti-allergy medicine such as a nasal steroid can be first line management before surgical intervention in some patients.
  •  Active infection is another relative contraindication unless the urgent removal is necessary. In interval of 3 months or more is recommended between tonsil infections to reduce risk of operative hemorrhage. 

Complications 

Hemorrhage is the most common complication. An estimated 2-3% of patients have hemorrhage, and 1 of 40,000 patients die from bleeding. 

Pressure can be applied to a bleeding tonsil fossa by using a sponge and a long clamp.

Options to stop the bleeding are electrocautery of the tonsil bed, use of further topical hemostatics, or ligation of the ipsilateral carotid artery as the last resort. Diathermy is thought to be superior to ligation because of the risk of perforating large vessels with the needle. In severe situations, a sponge may be fixed in place by using sutures. Another last resort is ligation of other large vessels, such as the external carotid artery. 

Bleeding may be classified as intraoperative, primary (occurring within the first 24 hours), or secondary (occurring between 24 hours and 10 days). 

Other complications include the following: 

  • Pain (eg, sore throat, otalgia)
  • Dehydration (common in children who do not eat because of pain)
  • Weight loss (common in children who do not eat because of pain)
  • Fever (not common, usually related to local infection)
  • Postoperative airway obstruction (because of uvular edema, hematoma, aspirated material)
  • Pulmonary edema (occurs in people with true airway obstruction caused by tonsils)
  • Local trauma to oral tissues
  • Tonsillar remnants
  • Vocal changes (If the tonsils are large, the patient’s voice may be muffled.)
  • Psychological trauma, night terrors, or depression
  • Death (uncommon, usually related to bleeding or anesthetic complications) 

Late complications are nasopharyngeal stenosis and velopharyngeal incompetence. These complications are most likely to occur if adenoidectomy or uvulopalatopharyngoplasty is undertaken at the same time as tonsillectomy.

THE MODERN TONSILLECTOMY

History

Aulus Cornelius Celsus, a Roman physician and writer, was the first to describe a surgical removal of the tonsils, and stated “the tonsils are loosened by scraping around them and then torn out” with a finger. At the time, vinegar mouthwash and another medication were used to maintain hemostasis. A hook and knife method was described by Aëtius of Amida on the Tigris in the sixth century. The contributions from Paul of Aegina and Philip Syng Physick added to the techniques available for tonsil removal. Physick used forceps to extirpate the tonsil, which eventually transformed into the tonsil guillotine. In the late 1800s, Mackenzie improved upon the tonsillotome and made its use common for tonsillar surgery. Although all of these previous techniques illustrated various methods of tonsil removal, they do not describe removal of the entire tonsil. In 1906, William Lincoln Ballenger recommended complete removal of the tonsils with a knife while keeping the capsule intact. George Ernest Waugh of England is credited as the first to describe complete tonsil excision using careful dissection in 1909. Samuel Crowe reviewed 1000 tonsillectomies performed from 1911 to 1917. He described using the Crowe-Davis mouth gag and performing careful sharp dissection for tonsillectomy. Hemostasis and pain have always been important principles in performing and managing patients following tonsillectomy.

In the United States, tonsillectomy, along with adenoidectomy, has been among the most frequent surgeries performed from 1900 to present. There was a peak from the 1940s to 1950s, with 1.4 million tonsillectomies done in 1959. This number fell to 500,000 in 1979 and further to 340,000 in 1985. In 1996, 287,000 children underwent tonsillectomy. The indications for surgery for the tonsils and adenoids have changed, contributing to decline in numbers. Chronic infection was the primary surgical indication in the 1950s and 1960s. With the advent of antibiotics, the numbers of recurrent tonsillitis have declined. Today, airway obstruction and obstructive sleep apnea are more common preoperative indications for surgery. 

Indications for Tonsillectomy

                                          

 Paradise, et al. conducted parallel randomized and non-randomized clinical trials for the efficacy of tonsillectomy in the pediatric population with recurrent episodes of pharyngitis. Their stringent criteria included rate of occurrence, clinical features, treatment and documentation. 7 or more episodes in the previous year, 5 or more episodes in each of the previous 2 years, or 3 or more episodes in each of the previous 3 years met their frequency standards. The clinical features of the each the episodes of pharyngitis included fever, cervical lymphadenopathy, tonsillar or pharyngeal exudates, or a positive ß-hemolytic streptococcus test. The treatment of these episodes required the administration of antibiotics. The results this study indicated that tonsillectomy was efficacious for 2 years, and possibly a third, in reducing the frequency and severity of subsequent episodes of phayngitis.

 The American Academy of Otolaryngology-Head and Neck Surgery Clinical Indicators Compendium in 1995 published the following indication guidelines for tonsillectomy:

  • Patient with 3 or more infections of tonsils and/or adenoids per year despite adequate medical therapy.
  • Hypertrophy causing dental malocclusion or adversely affecting orofacial growth documented by orthodontist.
  • Hypertrophy causing upper airway obstruction, severe dysphagia, sleep disorders, or cardiopulmonary complications.
  • Peritonsillar abscess unresponsive to medical management and drainage documented by surgeon, unless surgery performed during acute stage.
  • Persistent foul taste or breath due to chronic tonsillitis not responsive to medical therapy.
  • Chronic or recurrent tonsillitis associated with the streptococcal carrier state and not responding to beta-lactamase-resistant antibiotics.
  • Unilateral tonsil hypertrophy presumed neoplastic.
  • Recurrent suppurative or otitis media with effusion. (Adenoidectomy alone. Tonsillectomy added requires one of the indications listed above.)

In 2002, Paradise, et al. published another study also conducted as 2 parallel randomized, controlled trials to evaluate the efficacy of tonsillectomy in moderately affected children. Their surgical criteria were not as stringent, and their results indicated that the incidence of pharyngitis in the surgical groups was significantly lower than the control groups for the 3 ensuing years. However, the number of episodes in the control groups was also low, with a 7.9% incidence of surgery-related complications. They concluded that the current official guidelines were not sufficiently stringent for use in clinical practice.

Innovative Tonsillectomy Techniques

As described earlier in the history of tonsil surgery, there has been an evolution of various techniques to improve upon the postoperative morbidities following tonsillectomy. From tonsil scraping with blunt finger dissection without anesthesia to the use of a plasma field for dissection, there have been great strides in the development of modern tonsillectomy techniques. The use of the harmonic scalpel, microdebrider, coblation, and laser for excision of the tonsils are among the newer techniques used. The thrust of these newer techniques is aimed at reducing the comorbidities associated with standard monopolar electrocautery for tonsillectomy. Intraoperative and postoperative hemorrhage, pain, advancement to regular diet and activity, and overall cost of these procedures have been analyzed in many studies. The degree of thermal injury and disruption of subcapsular tissues are variables examined in many the newer techniques. Several select studies are presented here.

Intracapsular Tonsillectomy

                                          

Koltai, et al. performed a retrospective case series to review the use of intracapsular tonsillectomy using powered instrumentation for managing tonsillar hypertrophy causing sleep disordered breathing in children. A microdebrider set at 1500 rpm in the oscillating mode was used to perform the intracapsular tonsil resection, and a thin rim of lymphoid tissue was left on the capsule. Suction cautery was used for hemostasis. 150 children underwent intracapsular tonsillectomy and 162 children underwent total tonsillectomy. Of statistical significance, the intracapsular tonsillectomy group had lower pain scores at each measured interval in comparison to the total tonsillectomy group. In addition, the intracapsular group also had an earlier return to normal activity and less analgesic use. There was no statistical significance among the groups in the time required to resume a normal diet. This study concluded that if the tonsil capsule was left intact, the underlying pharyngeal musculature is undisturbed and isolated from secretions. This results in a decrease in postoperative pain and recovery time as compared to standard tonsillectomy. As with most retrospective studies, recall bias is a common concern.

In a retrospective review and follow up of 278 patients conducted by Sorin, et al. a 3.9% rate of complication from intracapsular tonsillectomy for tonsillar hypertrophy and obstructive sleep apnea in children was determined. There were a total of 11 complications in 278 patients. Nine patients had tonsillar regrowth with snoring. In addition, one had an immediate self-limited bleeding, and one with delayed bleeding.

Bent, et al. conducted a retrospective study to examine the safety and efficacy of performing intracapsular tonsillectomy in children under 3 years to challenge the paradigm that children under 3 years undergoing tonsillectomy require admission. The results indicated no statistically significant difference in pain, oral intake, or analgesic use in the < 3 years and > 3 years groups. In addition, no children in either group required admission.

Harmonic Scalpel Tonsillectomy

                                             

The harmonic scalpel is an ultrasonic dissector coagulator that utilizes ultrasonic vibration to cut and coagulate tissues. The cutting mechanism is possible with the sharp blade with a vibratory frequency of 55.5 kHz over a distance of 89 μm. The coagulation mechanism occurs by transferring mechanical energy to tissues. This breaks hydrogen bonds of proteins and generates heat from tissue friction. The temperature of the harmonic scalpel is lower than electrocautery (50° – 100° C, 150° – 400° C, respectively), and there is less thermal damage to tissues. The harmonic scalpel is an expensive product.

Walker and Syed evaluated 316 children undergoing tonsillectomy in a randomized trial to compare the harmonic scalpel (155) and electrocautery (161). There were no differences observed among the two groups in intraoperative blood loss or postoperative hemorrhage. The harmonic scalpel group had an earlier return to normal diet and activity. There was no significant difference in the frequency of use of narcotic or nonnarcotic analgesic agents.

Willging, et al. performed a single-blind, randomized prospective study to evaluate postoperative morbidity following the use of the harmonic scalpel versus electrocautery for tonsillectomy. 117 patients were enrolled, with 61 in the harmonic scalpel group and 59 in the electrocautery group. The indications for tonsillectomy included recurrent infection and hypertrophy with airway obstruction. Clinical outcomes measured included intraoperative bleeding, operative time, and postoperative hemorrhage. In addition, postoperative pain, ability to eat and drink and level of activity were evaluated with questionnaires. There was no statistically significant difference in intraoperative blood loss among the groups. Of significance, the intraoperative time for harmonic scalpel tonsillectomy was almost twice that of electrocautery (8 min 42 sec versus 4 min 33 sec, respectively). Although the harmonic scalpel group reported to sleep more soundly on the first three postoperative days, there was no significance in the ability to eat, drink, swallow and pain when speaking among the groups. Of interest, the level of activity in the harmonic scalpel group was significantly lower from surgery to the end of the first postoperative day. Postoperative pain scores tended to be lower in the harmonic scalpel group. The incidence of postoperative bleeding in the harmonic scalpel group was twice that of the electrocautery group, but this value was not statistically significant.

Laser Tonsillectomy

                                            

 The CO2 and KTP lasers have been used to perform tonsil surgery. D. Akin, in a series of more than 500 patients, observed less postoperative pain, more rapid healing, less blood loss, and less operative time using the CO2 laser.

Kothari, et al. conducted a prospective double-blind randomized controlled trial to compare the use of KTP laser tonsillectomy versus cold dissection and snare with bipolar cautery for hemostasis. A total of 151 children under the age of 16 years were enrolled with 72 in the dissection group and 79 in the laser group. Neither the patient nor the nurses were informed of the technique used. The KTP 532 laser was used at a 10 W continuous beam delivered with a 0.6 mm Endostat fiber. The outcomes measured were operative time, operative bleeding, postoperative pain, resuming a diet postoperatively, and admission or readmission rate. The laser group tended to require greater operative time (12 min) versus the dissection group (10 min), though not statistically significant. Of significance, the blood loss in the laser group (20 mL) was lower than the dissection group (95 mL). In addition, the laser group had significantly higher pain scores than the dissection group. The laser group also tended to have greater difficulty tolerating a diet two and three weeks postoperatively. Although the readmission incidence in the laser group was greater than the dissection group (8% and 4%, respectively), this was not statistically significant. This study concluded that the KTP laser provides little benefit over dissection tonsillectomy except to minimize intraoperative bleeding. This study does not take into account the surgical expertise required to perform an uncommon surgery such as laser tonsillectomy. In addition, it can be argued that electrocautery is currently the most frequent technique used for tonsillectomy, yet this was not included in this study.

Coblation

                                              

Coblation, or cold ablation, is a technique that utilizes a field of plasma, or ionized sodium molecules, to ablate tissues. Bipolar radiofrequency energy is transferred to sodium ions, creating a thin layer of plasma. This effect is achieved at temperatures from 40° to 85° C, in comparison to electrocautery which can reach above 400° C. The reduction in thermal injury to surrounding tissues offers reduced postoperative pain and morbidity.

Adjuvant Therapy

Postoperative pain and nausea are common following tonsillectomy. Adjuvant therapeutic techniques have been used to reduce the postoperative morbidity from tonsillectomy. These include the use of local anesthetic, dexamethasone intraoperatively, and postoperative antibiotics.

Local Anesthesia

 The tonsils are innervated by tonsillar branches of the glossopharyngeal nerve, palatine nerves derived from the maxillary branch of the trigeminal nerve and from lingual branches of the mandibular division of the trigeminal nerve. Infiltration by a local anaesthesic at the upper and lower tonsil pole and the anterior and posterior pillars anaesthetize these branches. Bupivicaine is an amide-linked local anesthetic with high lipid solubility and protein binding, giving a rapid onset and a prolonged effect of 6–9 h. In a prospective, double-blind, controlled study by Violaris and Tuffin, the application of topical bupivicane was compared to saline following tonsillectomy. They reported that the side treated with normal saline actually fared better, with less pain, than the side coated with 0.5% bupivacaine. Jebeles et al infiltrated the tonsillar fossae of children with bupivacaine and reported a marked reduction in pain after tonsillectomy even beyond the first week after surgery.

Nordahl, et al. conducted a prospective double-blind randomized clinical trial with three treatment arms to evaluate whether postoperative pain was influenced by injection of bupivacaine prior to tonsillectomy incision. 126 patients were evaluated, age 6 years and older, with exclusion of comorbid conditions including bupivacaine allergy. After randomization, 42 patients were in the saline (9mg/ml) arm, 41 in the saline (9mg/ml) with epinephrine (5μg/ml) arm, and 43 in the bupivacaine (2.5mg/ml) with epinephrine (5μg/ml) arm. About 5 minutes after anesthesia induction, the bilateral peritonsillar fossae were infiltrated with 5ml of study solution and tonsillectomy was performed 5 minutes later. The tonsillectomy technique was not specified but was indicated to be performed in a standardized manner for all cases. Pain measurements, including pain when swallowing, were recorded using a visual analog scale at standardized intervals following the tonsillectomy. The only statistically significant pain score among the groups was with the value of pain when swallowing. In addition no statistical significance was noted in the consumption of analgesics (paracetamol) among the treatment arms. Among patients operated on by an experienced otolaryngologist, those injected with bupivacaine and epinephrine tended to report less pain than patients in the other two treatment groups. In contrast, among patients operated by an ENT surgeon with little experience, patients in the bupivacaine and epinephrine group had the highest pain scores. Overall, this study concluded that bupivacaine injection does not provide a significant improvement in postoperative analgesia following tonsillectomy in an unselected group. Teenagers tended to have less analgesia from bupivacaine, but due to small sample size of age groups, this is not a precise conclusion.

Kountakis conducted a prospective, randomized, blinded and controlled study in Houston, TX, using local infiltration of 10 mL 0.5% bupivacaine solution versus infiltration with 10 mL of normal saline to examine the effectiveness of perioperative local anesthesia in tonsillectomy patients age 18 and older. 34 patients were entered in the study, but only 20 patients completed the questionnaires. After randomization, patients had the selected solutions infiltrated into the uvula, and bilateral anterior and posterior pillars. The technique used was electrocautery with blood loss up to 5ml and no reported complications. The questionnaire was completed daily for 10 days, and included a pain scale, amount of pain medicine taken and oral intake. The bupivacaine group initially faired better with a lower pain rating until about the 4th postoperative day. On postoperative day 4, the bupivacaine group reported greater pain than the saline group and this continued until the 10th day. Similarly, patients in the bupivacaine group consumed less pain medication initially, but this reversed on the 4th posterative day and required greater oral analgesics through the 10 days. Oral intake was relatively equal in the two groups for the first two postoperative days, but this again changed by the 3rd day and the saline group had greater oral intake through to the 10th day. Interestingly, there was no statistical significance in pain, pain medicine consumption, and oral intake between the groups.

Dexamethasone

Dexamethasone has been shown to be effective as an antiemetic agent in randomized trials with chemotherapy. Although, the exact mechanism by which dexamethasone exerts its antiemetic effect is unknown. The euphoric effects of steroids have been well documented, and the administration of dexamethasone for a painful surgery such as tonsillectomy seems reasonable. Its biological half-life is 36 – 72 hours.

Steward, et al. conducted a meta-analysis to evaluate the reduction of postoperative emesis, pain, and return to soft or solid diet. A total of eight double-blinded, randomized, controlled studies analyzing dexamethasone in children undergoing tonsillectomy or andenotonsillectomy were included in the meta-analysis. A single dose of intraoperative dexamethasone with dosing 0.15 – 1.0 mg/kg was administered. Sensitivity analyses were performed to statistically evaluate the impact of study exclusion attributed to missing data or varying measuring standards. In the first 24 hours postoperatively, the placebo group was twice as likely to have an episode of emesis than the dexamethasone treated group. The number needed to treat with dexamethasone to avoid one case of postoperative emesis was calculated to be 4.17. Also, the group treated with dexamethasone resumed a diet in the first postoperative day more often than the placebo group. Although the dexamethasone group tended to resume a diet by the third postoperative day more often than the placebo group, this was not statistically significant. Regression analysis determined that a dose of 1mg/kg for would have a beneficial antiemetic effect. The analysis of pain was not done due to missing data and varying outcome measures. No adverse events occurred as a result of dexamethasone administration. This study concluded that given the low cost and no reported adverse outcomes with dexamethasone, its administration for tonsillectomy seems reasonable to help prevent emesis in the first 24 hours after surgery and resume a diet in the first postoperative day. By performing sensitivity analyses, this study also addressed the problem of selection bias in the meta-analysis.

Carr, et al. performed a double-blinded randomized controlled trial to evaluate postoperative pain from electrodissection tonsillectomy after single intraoperative dose of dexamethasone in adults. There were no statistically significant differences between the dexamethasone and placebo (saline) groups, but the dexamethasone group tended to report less pain over the initial postoperative days. The dexamethasone group required less analgesic postoperatively, but there were no differences among the groups over 10 days.

Postoperative Antibiotics

Adjuvant postoperative antibiotics are used to decrease the inflammation of pharyngeal tissues following tonsillectomy due to colonization of bacteria. The benefits of antibiotics also include pain reduction, improving oral intake and possibly decreasing postoperative bleeding. Although, there is controversy to the use of antibiotics due to growing concern for bacterial resistance. Telian et al conducted a randomized controlled trial to evaluate the effect of ampicillin on recovery from tonsillectomy in children. The ampicillin group had significantly fewer fevers, improved oral intake, and required fewer days to normal activity.

Colreavy, et al. examined the use of amoxicillin/clavulanic acid in a randomized controlled trial in children. 78 patients were randomly assigned to either receive antibiotics or not. They compared tonsillar core, surface and postoperative tonsil fossa bacterial colonization profiles in the two groups. Bipolar tonsillectomy was performed in both groups. Their results indicated tonsil core bacteria were H. influenze (64%) 9.5% of which produced ß–lactamase, Step viridans (55.9%), S. aureus (37%) 86% of which produced ß–lactamase, and anaerobes (25%). More importantly, the pain scores, days to normal diet, and analgesic use in the group treated with antibiotics were significantly lower. This study concluded that it is logical to treat chronic carriers of ß–lactamase producing organisms following tonsillectomy with amoxicillin/clavulanic acid.

O’Reilly, et al. conducted a randomized double-blind controlled prospective trial of the effect antibiotics in adults following tonsillectomy. The antibiotic group received intraoperative and postoperative antibiotics. Patients were questioned at follow-up or sent a questionnaire to assess postoperative bleeding, postoperative pain, and if their PCP was contacted. The technique used varied, but electrocautery was most commonly used. The results of this study indicated that antibiotics had no influence on postoperative pain and bleeding. However, there were significant weaknesses in this study. This study had a high drop out rate, and recall bias.

Current Practice Patterns 

In 2004, Krishna, et al. published their results of a 13 question survey mailed to a small percentage of AAO-HNS members to evaluate the practice patterns of otolaryngologists with regard to tonsillectomy. The questionnaire included the technique used most and why, the use of local anesthetic, the use of steroids, and the use of postoperative antibiotics. Sharp dissection was the technique used most frequently among otolaryngologists in practice more than 20 years, while monopolar electrocautery was the technique used most often as a whole and by those in practice between 5-20 years. The reason for the preferred method of tonsillectomy was most commonly decrease in blood loss. The monopolar electrocautery group stated low blood loss as the primary reason for the technique used, while the sharp dissection group cited decreased postoperative pain the primary reason. The use of local anesthetic was splint nearly evenly within the study. Although the majority of the respondents stated the use of perioperative steroids, those in practice for more than 20 years were less likely to use steroids. In addition, the reasons stated for the use of steroids were to decrease pain, decreased nausea, and decrease swelling. Most used postoperative antibiotics, and cited decreased pain, decreased inflammation or faster healing as the primary reasons.

VOCAL CORD PARALYSIS AND VOCAL CORD MEDIALIZATION

                             

Anatomy 

The cartilages of the larynx consist of the thyroid cartilage, the epiglottis, the cricoid cartilage, and the arytenoid cartilages. The corniculate and cuneiform cartilages stiffen the aryepiglottic folds. The arytenoid cartilages articulate with the cricoid by means of a true synovial joint. This joint allows two movements of the arytenoid cartilages – rotation and lateral gliding. 

                                    

There are three groups of intrinsic laryngeal musculature – the abductors, adductors, and tensors. The only abductor of the larynx is the posterior cricoarytenoid muscle and it is innervated by the recurrent laryngeal nerve. The adductors are composed of the lateral cricoarytenoid muscle, interarytenoid muscle, oblique arytenoid muscles, and thyroarytenoid muscles. Innervation of the adductors is again supplied by the recurrent laryngeal nerve. The tensors are composed of mainly the cricothyroid muscle, which is innervated by the external branch of the superior laryngeal nerve, and to a lesser extent by the thyroarytenoid muscles. 

The true vocal folds have an epithelial lining that is composed of respiratory epithelium (pseudostratified squamous) on the superior and inferior aspects of the fold and nonkeratinizing squamous epithelium on the medial contact surface. The subepithelial tissues are composed of a three-layered lamina propria based on the amount of elastin and collagen fibers. The superficial layer is composed of mostly amorphous ground substance and contains a scant amount of elastin with few fibroblasts – this layer is termed Reinke’s space. The intermediate layer has an increased elastin content. The deep layer has less elastin but a greater amount of collagen fibers. The intermediate and deep layers have a higher concentration of collagen fibers and are termed the vocal ligament. Deep to the lamina propria is the thyroarytenoid (or vocalis) muscle. Reinke’s space and the epithelial covering are responsible for the vocal fold vibration.

The Vagus: 

                                                       

Understanding the anatomy of the vagus nerve is important because branches of the vagus nerve are responsible for innervation of the larynx. The vagus nerve has three nuclei located within the medulla:

  • The nucleus ambiguus
  • The dorsal nucleus
  • The nucleus of the tract of solitarius

The nucleus ambiguus is the motor nucleus of the vagus nerve. The efferent fibers of the dorsal (parasympathetic) nucleus innervate the invuluntary muscles of the bronchi, esophagus, heart, stomach, small intestine, and part of the large intestine. The efferent fibers of the nucleus of the tract of solitarius carry sensory fibers from the pharynx, larynx, and esophagus.

Vagus means “wanderer” which is appropriate for the path this nerve takes after emerging from the jugular foramen. It has two ganglia, the smaller superior ganglion and the larger inferior, or nodose, ganglion. The vagus sends small meningeal branches to the dura of the posterior fossa and an auricular branch, which innervates part of the external auditory canal, the tympanic membrane, and skin behind the ear. In the neck, the vagus runs behind the jugular vein and carotid artery to send pharyngeal branches to the muscles of the pharynx and most of the muscles of the soft palate. The superior laryngeal nerve separates from the main trunk of the vagus just outside the jugular foramen. It passes anteromedially on the thyrohyoid membrane where it is joined by the superior thyroid artery and vein (see vasculature). At approximately this level, the external laryngeal nerve leaves the main trunk. The main internal laryngeal nerve enters the thyrohyoid membrane through a hiatus. It then divides into three set of branches (ascending, transverse and descending), which communicate with the recurrent laryngeal nerve posterior to the cricoid cartilage; this is referred to as the ansa galeni. The internal superior laryngeal nerve penetrates the thyrohyoid membrane to supply sensation to the larynx above the glottis. The external superior laryngeal nerve runs over the inferior constrictor muscle to innervate the one muscle of the larynx not innervated by the recurrent laryngeal nerve, the cricothyroid muscle. 

The right vagus nerve passes anterior to the subclavian artery and gives off the right recurrent laryngeal nerve. This loops around the subclavian and ascends in the tracheo-esophageal groove. It tends to run with the inferior thyroid artery for part of its course before it enters the larynx just behind the cricothyroid joint. It may branch prior to this with sensory fibers supplying sensation to the glottis and subglottis. The left vagus does not give off its recurrent laryngeal nerve until it is in the thorax, where the left recurrent laryngeal nerve wraps around the aorta just posterior to the ligamentum arteriosum. It then ascends back toward the larynx in the TE groove. The vagus then continues on into the thorax and abdomen contributing fibers to the heart, lung, esophagus, stomach, and intestines as far as the descending colon. 

Normal function/movement/physiology 

The larynx has a variety of functions. It acts as a sphincter to close the airway during swallowing, preventing aspiration of food and liquids. This is phylogenetically the oldest and perhaps most important function of the larynx. Its function is also essential for respiration. Since the larynx is the gateway to the airway, laryngeal disease may result in obstruction of the airway. It functions during communication of both intellectual and emotional expression. Thus, voice deterioration is only one symptom of laryngeal dysfunction. It also stabilizes the thorax by preventing exhalation, this helps stabilize the arms during lifting. During coughing, lifting, and straining it compresses the abdominal cavity. Aspiration on swallowing, ineffective cough, and breathy voice are symptoms caused by the loss of sphincteric function, and can occur in addition to hoarseness in patients with true vocal fold paralysis. 

Phonation is defined as the physical act of sound production by means of passive vocal fold interaction with the exhaled airstream. Basically, this sound production arises from a passive movement of the true vocal cords (TVC)s modified in terms of pitch, quality, and volume by complicated interaction of thoracic and abdominal muscles, intrinsic and extrinsic muscles of larynx, and the shaping and resonance of the upper airway and nasal passages. Contraction of the expiratory muscles produces a rise in subglottic air pressure causing rapid escape of air between the nearly apposed TVCs. Bernoulli’s effect and the elasticity of the cords causes medial displacement of the medial edges of cords and airflow is stopped. A rapid rise again in subglottic pressure causes the cords to part and the cycle is repeated. It is the escape of small puffs of air that produces the vibratory phenomenon interpreted as sound. 

During phonation the lower margins of the true vocal folds separate first with formation of a volume of subglottic air. As the upper margins of the vocal folds separate a burst of air is released – the glottal puff. The lower fold then returns to midline, followed by the upper margin. This delay between closure of the lower and upper margins of the fold is termed the phase delay. The mucosal wave consists of both a horizontal movement of the folds and a vertical undulation. 

The body-cover theory helps explain this mucosal wave. It states that there are two layers of the vocal folds with different structural properties. The cover is composed of stratified squamous epithelium and the superficial layer of the lamina propria (Reinke’s space). The body of the fold is composed of the intermediate and deep layers of the lamina propria (which is more fibrous than the superficial layer – the “vocal ligament”) and the thyroarytenoid (vocalis) muscle. The cover is pliable, elastic, and nonmuscular, whereas the body is more stiff and has active contractile properties that allows adjustment of stiffness and concentration of the mass. The mucosal wave occurs primarily in this loose cover of the fold. Changes in stiffness or tension in the fold alters the mucosal wave. As the stiffness in the fold increases – as by contraction of the cricothyroid muscle – the velocity of the wave increases and the pitch rises. Mucosal wave velocity also increases with greater airflow and greater subglottal pressure. 

The pitch of voice is related to the fundamental frequency of vocal fold vibration (measured in hertz). The fundamental frequency of vocal fold vibration correlates with changes in vocal fold tension and subglottic pressure. Contraction of the cricothyroid muscles, which correlates positively with vocal fold tension, is the main predictor of fundamental frequency, especially at high frequency. Contraction of the thyroarytenoid may change the tension of the vocal fold cover and body and affect the fundamental frequency also. Three physical properties of the vocal folds determine frequency of vibration – mass, stiffness, and viscosity 

Mass – the fundamental frequency of vocal fold vibration is inversely proportional to its mass. Decreasing the mass – thinning of the fold by longitudinal stretching (contraction of the cricothyroid muscle with elongation of the vocal folds) – increases the frequency of vibration. Increasing the mass – contraction of the thyroarytenoid muscle with increased concentration of the fold – will decrease the fundamental frequency. 

Stiffness – vocal fold tension is an important variable in the control of fundamental frequency at the mechanical level. Vocal fold tension is affected by the contractile forces of the vocal fold musculature and the tissue characteristics of the vocal fold body, cover, and the connecting fiber structure of the vocal folds. 

Viscosity – Viscosity is inversely related to ease with which the tissue layers slip over one another in response to a shear force. Increased viscosity of the vocal folds would require greater subglottal pressure to maintain the same vibratory characteristics. Therefore, hydration of the vocal folds has effect on the voice quality and ease of voice production.

PATHOLOGY AFFECTING VOICE: 

                                                        

Unilateral Vocal Cord Paralysis: When one of the vocal cords is paralyzed, the cords are not able to meet in the midline to initiate the glottic attack. This prevents development of the subglottic pressure needed to initiate speech.. Also with the cords at such a distance, the mucosal wave cannot be adequately maintained. Hoarseness and breathiness are the most common complaints but vocal abnormalities may also include easy fatigability and voice or pitch change. It is important not to assume that the immobile cords are necessarily paralyzed. Arytenoid fixation can lead to an immobile cord and direct palpation of the arytenoid cartilage and/or laryngeal EMG can rule out this possibility. Potential return of function of an immobile cord can be determined if the underlying cause is known and with the aid of LEMG. This contributes significantly to the choice of surgical procedure to correct the problem. It is also important to remember that the larynx has a number of functions in the human and dysphonia may not be the primary compliant. Patients may be suffering from dysphagia, coughing, or choking episodes, or stridor.

There are a number of different causes of unilateral vocal cord paralysis. Any entity affecting the vagus nerve along its course may result in decrease in function. The most common cause is non-laryngeal cancer which includes neoplasms of the head, neck, chest, and skull base. Neuritis associated with upper respiratory infection, syphilis, or other infectious sources may cause nerve dysfunction. Neurologic conditions such as CVA, multiple sclerosis and myasthenia gravis may also effect vocal cord functioning. General medical conditions such as diabetes mellitus may cause an isolated neuropathy giving rise to vocal paralysis. Lesions of the vagal nerve occurring higher in the brain and may present with multiple cranial nerve abnormalities. 

Vocal Fold Bowing: The inability of the folds to approximate at the midline decreases the ability to produce proper speech. Though it may be a normal change in the aging patient, it is also seen with muscular atrophy secondary to nerve sectioning or central neurologic conditions. With aging, changes in the lamina propria include a loss of elastic fibers, atrophy of submucous glands, increased fibrosis, and muscle atrophy. These changes result in an increased glottic gap and a number of perceptual changes. Geriatric patients may present with hoarseness, low pitch, imprecise articulation, or breathiness. 

PATIENT EVALUATION AND SELECTION:

-History: 

GENERAL: As always, obtaining a pertinent history is of utmost importance. One should determine the onset, duration, and severity of the dysphonia. As previously mentioned, the larynx is also crucial in protecting the lower respiratory tract and is a conduit of the upper respiratory tract. Therefore the patient may present with coughing and choking episodes, aspiration, stridor, dyspnea, dysphagia, or odynophagia (2). Intubation history and previous head and neck trauma are crucial pieces of information. It is important to know if the patient has had any previous laryngeal surgery or other head and neck surgery. 

VOCAL: A specific vocal history is also important. Many patients who present with vocal complaints have a disease entity that does not warrant surgical treatment. Aside from onset, duration, variability, and past vocal problems, history should include pertinent medical questions such as presence of seasonal allergies, history of reflux disease, life stress, diabetes, and medications. Many patients who present for an initial evaluation of voice complaints are unfamiliar with questions of vocal use and hygiene. It is important for the physician to explain these concepts to the patient during the questioning to facilitate accurate responses and educate the patient. Questions should include voice demands at home and at work, recreational singing, and episodes of abuse i.e. sporting events. Smoking, water intake, caffeine intake, and environmental irritants are important questions about vocal hygiene.-

Physical: 

It is important to do an entire exam with emphasis on palpation of the neck to assess for any neck mass or goiter and cranial nerve testing. An indirect laryngeal exam, as well as a flexible laryngoscopy or videostrobe should be performed. The patient should phonate a high pitched /ee/ sound. This causes elongation of the vocal folds and causes the larynx to move superiorly. These movements aid in obtaining a complete view of the larynx. In addition to assessing vocal fold position and mobility, it is crucial to rule out carcinoma of the larynx in a patient presenting with hoarseness. A direct laryngoscopy with palpation of the arytenoids to ensure joint fixation is absent should be done prior to any surgical procedure. 

The manual compression test is an easy non-invasive office procedure to help evaluate a number of voice disorders. The lateral manual compression test is particularly useful in determining whether a patient with a wide glottic gap from unilateral vocal cord paralysis or vocal bowing will benefit from a medialization thyroplasty. To perform the test, the neck should be palpated to find the superior notch and the inferior margin of the thyroid ala. The vocal cords are located along a horizontal line drawn at the midpoint of these two landmarks. The patient is asked to sustain an /a/ phonation and pressure is applied to the lateral aspects of the thyroid cartilage. The concept is to approximate the vocal folds and decrease the glottic gap. A subjective improvement in voice quality is sufficient to state that the patient would benefit from a medialization thyroplasty though acoustic, aerodynamic, and videostroboscopic studies can be done to quantify improvement. The limitations to this test are older patients who have calcification of the thyroid cartilage, patients with obese necks, and patients with scarring of the vocal folds. 

-Vocal Assessment: 

Despite the recent outburst of technology used to measure and quantitatively assess voice, there is no substitute for the trained ear. Taking a history gives ample time for the physician to make a qualitative assessment of the patient’s voice. Qualities such glottic fry, hard glottal attacks, breathiness, diplophonia, pitch breaks, phonation breaks, and tense phonation can be assessed. 

Acoustic evaluation is the quantitative measurement of various voice characteristics. Having the patient sustain a single tone, the fundamental frequency (Fo), variations in amplitude (shimmer), and variations in pitch (jitter) can be measured. Fo may be decreased in patients with vocal abuse or poor approximation of the vocal folds. Shimmer alteration is due to decreased stability of the vocal folds. Abnormal jitter correlates with the subjective quality of hoarseness. 

                         

Videostrobolaryngoscopy (VSL) should be performed whenever possible. It allows for dynamic assessment of the vocal folds. With this view, the physician is able to differentiate between functional voice problems and those caused by subtle structural abnormalities. Pulses of light allow us to watch various parts of successive cycles to obtain a complete picture of vocal cord activity. The physician is able to evaluate symmetry of movement, aperiodicity, glottic closure configuration, and horizontal excursion amongst other variables. If the cords are functioning symmetrically, they should essentially be mirror images of each other. The lateral excursion and timing of opening/closing should be identical. Aperiodicity is a measure of irregularities in vocal fold movement. If the frequency of the strobe light is equal to the fundamental frequency, no vocal fold movement should be seen. If movement is observed followed by a static period, aperiodicity is present. The glottis may also be assessed for gap, shape, and appropriate closure (11). The shape of the glottis may be characterized as complete, anterior chink, irregular, bowed, posterior chink, hourglass, or incomplete. Horizontal excursion is a measurement of the amplitude of the cords. Measurement both pre and post-operatively can provide objective data for evaluating improvement. An additional benefit is reviewing the results with the patient immediately after performing the examination. Giving the patient a visual image of the problem helps considerably in motivation for behavioral treatment and development of goals for improvement.

Electromyography (EMG), though not routinely performed, is an excellent evaluation of specific muscle functioning. By placing electrodes into laryngeal muscles (thyroarytenoid, cricothyroid), EMGs help elucidate whether there is any re-innervation of muscles which are thought to be paralyzed. It can also help to differentiate paralysis from arytenoid joint fixation. EMGs are also used to identify excessive muscle activity prior to the use of BOTOX for spasmodic dysphonia.

-Diagnostic Tests: 

If indirect or stroboscopic exam demonstrates a unilateral vocal cord paralysis with no known etiology, a specific battery of tests should be considered. A CT scan from skull base to the mediastinum should be done to evaluate the entire length of the vagus and recurrent laryngeal nerves. If the patient is a child, pregnant, or suspected to have a generalized neurologic problem, an MRI is advised instead. A barium swallow may be done to evaluate swallowing mechanism and associated dysphagia. Radioactive thyroid uptake scan or ultrasound may be done to evaluate for the presence of a nodule or tumor. Chest x-ray is performed to rule out the presence of a bronchogenic carcinoma, mediastinal adenopathy/mass, or less likely, the presence of an enlarged heart compressing the recurrent laryngeal nerve, particularly on the left side. A FTA-Abs test should be done to rule out syphilis as a cause of vocal cord paralysis.

TREATMENT OPTIONS: 

The most important aspect of rehabilitating voice is defining the patient’s goals. 

–VOICE THERAPY : 

Assessment of patients by a speech pathologist allows for maximal medical treatment to be implemented before consideration is given to surgical treatment. Some patients develop hyperfunctional compensatory mechanisms which lead to the common complaints of voice strain, neck discomfort, and fatigue (16). Speech pathologists can help eliminate these habits and educate the patient on proper compensation techniques. Relaxation exercises, aerobic conditioning, voice exercises and other methods are all practiced by the patient to improve voice quality. Once vocal therapy has been maximized and further voice improvement is desired, surgical options may be considered. Utilizing voice therapy in treatment of unilateral vocal cord paralysis is crucial to ensuring the greatest improvement in voice.

–CORD INJECTION:

 Teflon

Indications: Teflon injections are most commonly used for unilateral vocal fold paralysis with no hope for return of function in terminal patients. To ensure that function will not return, a waiting period of one year is usually observed prior to performing the procedure.

Contraindications: Experience has shown that Teflon injections are particularly poor when the voice complaint is secondary to vocal cord atrophy, or vocal fold bowing.

Procedure: There are a number of different approaches to injecting the vocal folds. When performing the percutaneous injection, no sedation is required and local anesthetic is used. Fiberoptic laryngoscopy is used concurrently to assure proper placement and adequacy of the injection. The lateral percutaneous approach requires the surgeon to pierce the thyroid cartilage at the level of the vocal fold. An anterior approach may be used by placing the needle through the cricothyroid membrane and angling the needle superiolaterally under direct visualization. The Teflon should be placed lateral to the vocalis muscle with great care not to disturb the endolaryngeal mucosa. The first injection should be placed anterolateral to the vocal process of the arytenoid. Teflon is injected until appropriate medialization is seen with fiberoptic laryngoscopy. Another bolus of Teflon is placed anterior to the junction of the middle and anterior one third of the cord. A transoral injection may be done under local anesthesia using indirect mirror laryngoscopy. It is extremely important to bevel the needle away from the mucosal edge to avoid an intramucosal injection. If the procedure cannot be adequately performed under local anesthesia, it may be done during a direct laryngoscopy under general anesthesia with jet ventilation. It is important not to place excessive pressure on the anterior commissure to avoid distorting the vocal cords. The needle is placed lateral to the vocal fold, 2mm deep, at the level of the vocal process. The patient is asked to phonate and further injections depend upon voice quality. It is important to asses voice quality during the procedure. If too much Teflon is injected, the results may be disastrous. If overinjection does occur, it is imperative to incise the mucosa over the site of injection and suction out the excess.

Advantages: The procedure is inexpensive and produces immediate results. It can also be done under local anesthesia and usually results in satisfactory voice. It is important to note that these advantages, once exclusive to Teflon injection, can be provided by other surgical procedures.

Limitations: The irreversibility of the procedure is a major concern. Teflon may only be placed in a vocal cord which has no potential for return of function. As stated above, this requires one year of waiting after initial presentation to ensure complete paralysis. The only exceptions to this is the terminally ill patient with aphonia or aspiration. If vocal fold function does return after placement of Teflon, voice quality will be poor with increased likelihood of displacement, extrusion, and granuloma formation. Teflon injection into a mobile cord will cause hardening of the cord and disruption of the normal mucosal wave. Attempts to remove a Teflon implant usually result in destruction of the vocal fold. The inability to use Teflon in cases with absent soft tissue is another criticism. This automatically eliminates its use in patients with atrophy and bowing of the vocal folds, status post cordectomy, and status post blunt laryngeal trauma (9). The injection of Teflon is not sufficient to medialize the cord and enhance vocal function. Patients suffering from a central neurologic problem also receive no benefit from Teflon injection. Central lesions typically disrupt superior laryngeal and pharyngeal function and therefore a procedure which narrows the glottic gap may not be sufficient to prevent aspiration. Migration of the implant and extrusion through the vocal membrane are other possible complications. Granuloma formation is the most feared complication. It can result in poor voice quality and eventually airway compromise. Because of this, Teflon is now limited by most.

Collagen 

Collagen injections are derived from bovine collagen which is modified to minimize host immune response. Collagen implants are assimilated into the surrounding tissues by an invasion of fibroblasts and deposition of new host collagen. Histologically, the collagen is similar to the deep layer of the lamina propria. Therefore, the collagen is placed within this layer of the vocal fold. Though there is some resorption of the collagen, this is offset by the deposition of host collagen thereby providing long term voice improvement. Resorption of the collagen may be precipitated by an upper respiratory infection. There have been reports of hypersensitivity reactions with rare cases of airway compromise with the use of Bovine collagen, Zyderm. Some authors still advocate the use of dermal skin tests to test for possible allergic reaction to the injections. In a series by Ford and Bless, 2 of 80 patients had a positive skin test which is consistent with the reported incidence of 3%. Recently, an increased used of Cymetra, a form of collagen composed of micronized homologous alloderm, has decreased the incidence of allergic reactions and lengthened the period of benefit. 

Autologous Fat 

In 1987, Brandenburg et al. reported the first use of autologous fat injection for glottic insufficiency. Since then, fat injection for a variety of etiologies has become very popular.

Indications: Fat injections have been used successfully in patients with vocal cord paralysis, vocal fold scarring, vocal fold atrophy, and intubation defect.

Contraindications: There are no definitive contraindications to fat injection

Technique: (as described by Hsiung et al. (12)). Under general anesthesia, fat is harvested from the lower abdominal pannus. The fat is cut into 1mm pieces separating it from connective tissue. The fat is then rinsed with lactated ringers followed by a methylprednisolone solution. It is then loaded into a syringe. The actual location of fat placement is dictated by the underlying pathology. For those patients with vocal cord atrophy and paralysis, the anterio- and posteriolateral areas of the middle third of the cord are injected. Injection is continued until a 50% overcorrection and convex bowing of the affected cord is seen.

Outcome: Since its first use in 1987, fat injections have gained popularity. Autologous fat is well tolerated in the vocal cord and repeated injections can be done if necessary. Unlike Teflon where overinjection can be disastrous, placing too much fat in the vocal fold does not cause significant post-operative complications. Overinjection is recommended because a certain percentage of fat will atrophy over time. Postoperative analysis reveals an improvement in glottic closure and mucosal wave production. Though there is an improvement in the breathy quality in those patients with glottic insufficiency, vocal roughness persisted after the procedure. Anterior defects corrected with fat injection have a better postoperative outcome than posterior defects. 

Hsiung et al. divided failure into two categories, early and late. With early failure, it was believed that it was due to 1) a large glottal gap or 2) a posterior defect not corrected with fat injection. Late failure was attributed to absorption of the fat supported by an initial improvement in voice quality. 

There are still a few concerns and questions about fat injection. Knowing that there will be some reabsorption of the fat, the cord needs to be overinjected. This leads to the question of exactly how much fat results in an optimal change in voice. It is also not known whether improved vocal function is due to the amount of fat injected or softening of the vocal cords. Another uncertainty is the rate of fat absorption by the vocal tissue. If initially effective, the benefits of fat injection may last anywhere from three months to several years. Some studies have shown that despite absorption of the fat, lipocytes and fibrous connective tissue retain the contour of the vocal cord and provide long term benefit. The exact method of harvesting and preparation of the fat and its relation to absorption is still unknown. Effort should be made to minimize that amount of trauma to the fat during extraction.

Synthetic Injectables: 

Calcium Hydroxyapatite (Radiance FN; BioForm) is an injectable material made of small spherules of CaHydroxyapatite. No granuloma formation occurs with this agent. Long term efficacy is currently under study. 

Polydimethylsiloxane gel (Bioplastique; Bioplasty) is widely used in Europe for vocal fold medialization, but is not approved for use in the U.S. Sustained phonatory improvement up to 7 years has been shown in some European studies.

–TYPE I THRYOPLASTY

Indications: A Type I thyroplasty was repopularized by Isshiki in 1974. The indications for a Type I thyroplasty are unilateral or bilateral vocal fold paralysis or paresis, vocal fold bowing, and incomplete glottic closure with aspirations.

Contraindications: There are two contraindications for performing a Type I thyroplasty. The first is in patients with a previous hemilaryngectomy. Without the support of the thyroid cartilage, the silastic implant is ineffective in medializing the scarred side. Vocal fold injection is indicated in this case. The second contraindication is previous laryngeal irradiation due to extensive scarring.

Technique: There are many variations in this procedure championed by several authors. Described below, is the technique performed by Netterville et al (6). A horizontal incision is made over the midportion of the thyroid cartilage and the cartilage exposed. A window is created in the thyroid ala approximately 8mm posterior to the anterior commissure and 3mm superior to the inferior border of the cartilage. This provides a sufficient strut inferiorly to support the implant. After the window is made, the cartilage is removed. Incisions are made in at the inferior, posterior and superior aspects of the inner perichondrium thereby creating a flap. The perichondrium is elevated from the medial aspect of the thyroid ala. While viewing the cords via fiberoptic laryngoscopy, a depth gauge is used to medialize the cords in the anterior, middle, and posterior aspects of the window and the measurements are recorded. These measurements are also taken at the superior and inferior aspects of the window to find the relation between the true and false vocal cords. Using measurements from the various areas of the windows, an implant can be fashioned from a silastic block. The point of maximal medialization is at the level of the vocal process. Very minimal medialization is designed at the anterior commissure to prevent a strained voice. The inferior aspect of the implant is placed in the window and rotated into place. The patient is asked to phonate and voice is assessed. If medialization is not optimal, the implant can be removed and modified. The time of intralaryngeal elevation and implant placement should be minimized to prevent vocal interference by intraoperative edema.

-Variations/Controversies: 

Removal of the cartilage window: Some authors feel that the cartilage, if left in place can migrate superiorly and medialize the false vocal cord or ventricle. If the cartilage migrates inferiorly, it may cause overmedialization of the cord resulting in a persistently strained voice quality.

Inner perichondrium: Some authors prefer to leave the inner perichondrium intact stating that it decreases the incidence of graft extrusion. Netterville states that the reason for increased implant extrusion is injury to the ventricle. This occurs more frequently if a paramedian incision is used near the anterior commissure where the ventricle is located very close to the inner perichondrium. He argues that incising the inner perichondrium does not increase implant extrusion secondary to the development of a fibrous capsule around the implant.

Implant material: Though some authors feel that a carved implant allows for precise results, Montgomery et al. (10) reports certain benefits to a pre-made implant. The inner aspect, which medializes the cord, is made of a softer plastic closer to the consistency of the surrounding tissue. The outer half is made of a harder plastic which locks into the thyroid cartilage. This prevents displacement of the cords and eases revision. Hydroxylapatite is a pre-made implant which has minimal tissue reactivity and good biocompatibility with the surrounding tissue. Gore-tex (ePTFE) is another material reported to be of benefit in medializing a paralyzed vocal cord. This material has excellent biocompatibility and can be used to medialize the cord in an incremental fashion. This technique does not require extreme precision in creating the thyroid window or shaping the implant.

Benefits: Type I thyroplasty has had excellent results in voice improvement. The procedure helps to re-establish the mucosal wave in the paralyzed vocal fold. By approximating the vocal membranes, normal anatomic position is re-established and the cords are able to produce sound. The return of an intact mucosal wave is a large reason that this procedure is so effective in improving voice. This improvement is illustrated by an increased Fo and maximum phonation time. Other objective variables such as glottic closure and cord symmetry are also improved. The improvement in aspiration symptoms is even more consistent than the improvement in voice quality. Additional benefits include the ability to monitor vocal improvement during the procedure if performed under local anesthesia. Using a nasopharyngoscope, the surgeon can ensure the implant is at the level of the true vocal cords and not medializing the false cords or the ventricle. It is both adjustable and potentially reversible. The reversibility of the procedure allows its use in a patient with potential return of vocal cord function. The implant can also be revised if the vocal cord continues to atrophy over time. When performing a Type I thyroplasty, it is important to council the patient on the expected voice changes post-operatively. Though initially strong in the operating room, perioperative edema will cause the patient to be hoarse for the first ten days after the procedure. Some have noted an additional period of voice difficulty occurs 4 to 6 weeks after surgery. This eventually improves and the patient’s voice may continue to improve for the next year. Primary medialization thyroplasty occurs at the time of extirpative surgery with known

sacrifice of the recurrent laryngeal nerve in the neck. This procedure is done under general anesthesia and therefore negates the benefit of intraoperative voice evaluation. It is performed primarily in hope to eliminate the need for a tracheotomy and decrease the postoperative rehabilitation time (swallowing and speech) of patients with loss of multiple cranial nerves.

Complications of a Type I thyroplasty include persistent dysphonia, airway obstruction, implant migration, extrusion, hematoma, and infection. Poor voice quality post-operatively may be due to inadequate medialization or over-medialization of the cords. Appropriate voice assessment can only take place 4 to 6 weeks after the operation when all edema has resolved. Despite various techniques to prevent migration, occasionally the implant may move superiorly and medialize the false cord and ventricle. This calls for removal of the implant and replacement with a larger prosthesis. Extrusion into the airway is a serious complication. Though it does not occur frequently, suspicion should warrant a fiberoptic laryngoscopy and subsequent endoscopic extraction if found. Extrusion laterally can be avoided by securing the prosthesis firmly in the thyroid cartilage. In general, complications can be reduced by careful handling of the tissues, limited operative time, and meticulous hemostasis 

Type I thyroplasty may not be sufficient to close a large posterior gap. It may difficult to know pre-operatively whether posterior approximation will be needed. One method proposed by Omori et al.(5) is to obtain videostroboscopic measurements prior to surgery. They assessed the posterior glottic gap as a percentage of the membranous vocal fold length. They found that is the posterior glottic gap was larger than 10% of the membranous vocal fold length, the post-operative outcome was worse and a posterior closure procedure may be warranted. If it is determined that the posterior gap is too large either pre or intra-operatively, the surgeon has the option of either creating an implant with a large posterior component or performing an arytenoid adduction (discussed later). Implants that were originally fashioned to medialize the posterior cord did so by pressing on the vocal process of the arytenoid cartilage. It has since been shown that it is more effective to fashion the implant to apply pressure to the muscular process of the arytenoid. Simply stated, the implant should have a large posterior flange, approximately 5mm in thickness to fit between the muscular process and the thyroid ala. The major advantage of this procedure is, unlike arytenoid adduction, that it does not hinder mobility of the vocal folds. 

–ARYTENOID ADDUCTION:

                                          

There are two major indications for an arytenoid adduction. The first reason is to close a posterior glottic gap. Given that the cricoid overlaps the thyroid posteriorly, a posterior window is not effective in medializing the posterior vocal cord. The traditional Type I thyroplasty has been shown to be ineffective in medializing the posterior cord. A simple way to assess if an arytenoid adduction is necessary is to see if the vocal processes of the arytenoid cartilages touch in the midline when the patient phonates. The second reason is if the vocal folds are not at the same caudal-rostral level. The vocal process of the arytenoid cartilage moves inferior with adduction and superior with abduction. This is due to the cylindrical shape of the cricoarytenoid joint. Some surgeons advocate an intra-operative assessment of the vocal cord medialization. If after the silastic implant has been placed, there is a persistent posterior gap, an arytenoid adduction is performed. 

The procedure is described as it is performed by Isshiki. Using a horizontal neck incision at the level of the vocal cords, the posterior border of the thyroid cartilage is exposed by transecting the strap muscles and detaching the inferior constrictor from the thyroid. It is important to identify the recurrent laryngeal nerve in this area to avoid any damage. The cricothyroid joint is then opened to allow access to the muscular process of the arytenoid cartilage. The piriform sinus mucosa is then elevated with great care to violating the piriform recess. Cricoarytenoid joint is then opened allow exposure of the muscular process. The posterior cricoarytenoid muscle is identified and ligated from the muscular process. Two 3-0 nylon sutures are placed around the muscular process and the surrounding soft tissue. The sutures are then pulled anteriorly through the thyroid ala. The patient is asked to phonate and the appropriate force is determined to provide optimum voice results. 

The only significant variation is whether or not to open the thyroarytenoid joint. Some authors believe that opening the joint results in prolapse of the arytenoid cartilage into the laryngeal lumen with overadduction of the posterior commissure.

Arytenoid adduction can be used in conjunction with medialization thyroplasty and re-innervation surgery. Currently, no other procedure corrects for a discrepancy in vocal cord level and few other procedures effectively address a wide posterior chink. 

–REINNERVATION SURGERY WITH ANSA CERVICALIS:

Indications: In the past few decades, there has been a surge of interest in reinnervation surgery as a therapy for unilateral vocal cord paralysis. Given that the arytenoid cartilage is mobile and the ansa cervicalis has not been disrupted, reinnervation with a nerve-muscle pedicle or recurrent laryngeal nerve – ansa cervicalis anastomosis should be considered.

Contraindications: If there is any fixation of the arytenoid cartilages, a nerve anastomosis should not be used. This procedure cannot be performed on a patient who has had disruption of the ansa cervicalis, either by surgery, trauma, or neurological process.

Neuromuscular pedicle reinnervation: An incision is made in the lower half of the thyroid ala extending to the sternocleidomastoid muscle. The ansa cervicalis is identified overlying the jugular vein and is traced to its insertion to the anterior belly of the omohyoid muscle. Two stay sutures are placed 2-3mm proximal and distal from the insertion site. A window is made is similar to that used for a Type I thyroplasty. The inner perichondrium is opened and the thyroarytenoid is incised superficially. Using the stay sutures, the muscle pedicle is sown in place. It is crucial to avoid excessive tension on the pedicle.

Ansa Cervicalis – Recurrent Laryngeal Anastomosis:The ansa cervicalis is exposed overlying the great vessels or within the carotid sheath. The ansa is traced to either the omohyoid or sternothyroid. The nerve is sectioned at its insertion to the muscle and transposed to the tracheoesophageal groove. The recurrent laryngeal nerve is identified by retracting the superior thyroid neurovascular bundle and followed to its insertion into the larynx. The nerve is ligated 7 –10mm from its insertion in the larynx to ensure a tension free anastomosis. The nerves are anastomosed with a neurorrhaphy (epineural repair) with 10-0 suture under magnification.

Outcomes: Re-innervation surgery has recently gained popularity in those patients with unilateral vocal cord paralysis. Though cord injections, medialization thyroplasties, and arytenoid adduction are sufficient to medialize the cord and close the glottic gap, none of these procedures address vocal fold tone, another important component of speech production. Reinnervation surgery provides tone to the thyroarytenoid muscle and gives tension to the vocal fold. Another reason cited to perform reinnervation is to prevent vocal fold atrophy. If a medialization procedure is performed, it may need to be revised 2 to 3 years later because cord atrophy has resulted in an increased glottic gap. Laryngeal reinnervation maintains the bulk of the paralyzed fold. Currently it is not known as to the optimal time to perform reinnervation surgery and which patients it will benefit. It has been proposed that intraoperative EMG can distinguish those patients with no spontaneous reinnervation from those with inappropriate reinnervation (synkinesis). Those patients with no spontaneous reinnervation would be more likely to benefit from operative reinnervation.

A universal criticism of reinnervation is the 4 to 6 month period required for the procedure to be effective. Many authors advocate the concurrent use of a medialization procedure, either Gelfoam injection or thyroplasty. Tucker has described removing the posterior inferior aspect of the implant in order to allow room for the muscle-pedicle implant to be placed. 

When comparing the two methods of reinnervation, it is currently unclear which procedure produces the best results. Preliminary work by Hall et al. indicates that the muscle pedicle allows for more rapid innervation and stronger contractile force. Current research is directed toward understanding the role of cell adhesion markers in the role of nerve regrowth. This research will likely have a significant impact on the methods of reinnervation surgery. 

Recently a modification has been proposed to the recurrent laryngeal nerve – ansa recurrent laryngeal anastomosis procedure. Paniello (16) has proposed a recurrent laryngeal – hypoglossal nerve anastomosis. The theoretical advantage is that these are the only two nerves involved in swallowing and phonation. Other advantages are an abundance of axons in the hypoglossal nerve, use in patients in which ansa is unavailable, and low donor site morbidity. Initial work with the procedure suggests that it results in a stronger reinnervation and sphincter-like action on swallowing. Though there is denervation of the ipsilateral tongue, no increase in aspiration has been shown

Bilateral Vocal Cord Paralysis: 

                                            

In contrast to unilateral vocal cord paralysis, voice quality is not the primary concern in patients with bilateral vocal cord paralysis. The significant problem is airway compromise. This can range from unnoticeable to, more commonly, dyspnea and stridor. The patient’s voice quality is usually only mildly affected (if just the recurrent laryngeal nerves are involved) because the paralyzed cords tend to assume the natural position for phonation.

There are three basic ways that bilateral vocal cord paralysis is managed:

  • Tracheotomy
  • Vocal cord lateralization
  • Reinnervation

Tracheotomy: 

                                                  

Tracheotomy has the advantages of providing immediate relief of airway restriction. It can be performed under local anesthesia, and has relatively little reduction in voice quality. Disadvantages include the creation of a stoma that has both cosmetic and long-term care problems, and the need to occlude the tube or wear a speaking valve to phonate. This may be the best option for many patients because it controls the airway while preserving voice quality. In many patients, the tracheotomy can be occluded the majority of the time. In times of exertion, while sleeping, or when the patient has a cold or other respiratory condition, the tracheotomy can simply be unplugged.

Vocal Cord Lateralization: 

                                         

This involves several techniques that surgically widen the glottic opening. While this improves the airway, the patient’s voice quality suffers. The three most commonly utilized techniques are arytenoidectomy, arytenoidopexy, and cordectomy/cordotomy.

Arytenoidectomy:

Classic arytenoidectomy involves removal of some or all of the arytenoid cartilage. This procedure can be performed in a variety of ways, from endoscopically by microsurgical or laser technique to an external, lateral neck approach (Woodman). The Woodman procedure involves a lateral neck incision, exposure of the arytenoid cartilage posteriorly with removal of the majority of the cartilage, sparing the vocal process. A suture is then placed into the remnant of vocal process and fixed to the lateral thyroid ala. This technique seems to cause less voice deficit than other approaches.

Arytenoidopexy: 

Arytenoidopexy displaces the vocal fold and arytenoid without surgical removal of any tissue. It can be done endoscopically with a suture passed around the vocal process of the arytenoid and secured laterally. This procedure, however, has a relatively high failure rate and is technically difficult. 

Cordectomy: 

                                                    

Dennis and Kashima (1989) introduced the posterior partial cordectomy procedure using the carbon dioxide laser. This involves excising a C-shaped wedge from the posterior edge of one vocal cord. If this posterior opening is not adequate after 6-8 weeks, the procedure can be repeated or a small cordectomy can be performed on the other vocal cord. Laser cordotomy removes a smaller posterior portion of the true vocal cord and better preserves voice.

 Reinnervation:

Tucker proposed a nerve-muscle transfer to the posterior cricoarytenoid muscle for the treatment of bilateral vocal cord paralysis. The technique is similar to the one used for unilateral vocal cord paralysis. Prerequisites are that the cricothyroid joint not be fixed and that the necessary nerve for the graft not have been affected by the process that caused the paralysis. Tucker reports a high success rate

 

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

 
Follow

Get every new post delivered to your Inbox.

Join 40 other followers

%d bloggers like this: