The thymus gland is one of the more common structures in the anterior mediastinum that requires surgical extirpation. Most commonly, the indications for thymectomy are either for thymic neoplasm or in the treatment of the autoimmune disorder, myasthenia gravis (MG). Thymus removal should be a safe, straightforward procedure. The key elements in successful and complete thymectomy depend on a comprehensive knowledge of the anatomic and embryologic characteristics of thymic development and the physiology of thymic disease.

The thymus lies in the anterior mediastinum. It is a lymphoepithelial organ that is derived embryologically from the third pharyngeal pouches bilaterally and descends caudally and medially into the mediastinum during gestation, fusing into a bilobed gland. However, fusion and descent are often variable and islands of tissue may be found throughout the neck and mediastinum. In addition to being embedded within the thyroid gland or associated with the parathyroid glands, aberrant thymic rests can occur independently along the entire path of thymic descent (Fig. 160-1).¹ The gland weighs 10 to 35 g at birth, attains its greatest mass in puberty (20–50 g), but involutes and is replaced by fat in adulthood. It occupies the anterior mediastinum, with the superior horns often extending into the neck, lying deep to the sternothyroid. At the completion of its development, the thymus is separated from the sternum by a thin film of loose connective tissue lying anterior to the pericardium and great vessels and is in especially close contact with the left brachiocephalic (innominate) vein. The gland can extend laterally to the phrenic nerves and is partially covered on either side by the pleural reflections. The arterial supply to the thymus is derived principally from the internal thoracic arteries, with contributions from the inferior thyroid, and pericardiophrenic arteries. The veins from both lobes ascend between the lobes posteriorly and usually drain into the left brachiocephalic vein or, rarely, directly into the superior vena cava. The inferior thyroid and thyroid ima veins can receive minor tributaries from the cervical portion of the gland. The phrenic nerves are in immediate proximity to the gland, as are the vagus and recurrent laryngeal nerves. Careful attention to the anatomy is essential for avoiding injury to these vital nerves (Fig. 160-2).

The thymus gland is a central lymphoid organ that performs the important immunologic function of transforming null lymphocytes into thymic or T-lymphocytes, which are responsible for cellular immunity. The maturation of T-lymphocytes appears to be promoted by one or more thymic-derived factors, such as the peptide thymosin. The thymus gland is involved in a variety of immunologic, hematologic, endocrine, infectious, and neoplastic diseases. The thymus can display morphologic changes that are associated with abnormal development, immune deficiencies, hyperplasia, and neoplasia. Symptoms may be related to the physical presence of the mass (compression or invasion), associated with a described clinical syndrome (MG, red cell aplasia, or hypogammaglobulinemia), or may be nonspecific (anorexia and fatigue). Failure of the thymus to descend into the anterior mediastinum might account for cervical thymic tissue, which can be mistaken for neoplasm, lymphadenopathy, or an enlarged parathyroid. This aberrant tissue can cause compressive symptoms such as respiratory stridor or dysphagia. In general, symptoms are more common and specific in patients with malignancy, whereas patients with thymic cysts and germ cell tumors have symptoms less frequently.

The indications for thymectomy are thymic neoplasm and MG. Thymoma is a neoplastic process of thymic epithelial cells. Often the malignant potential is not determined by the microscopic appearance, but by the behavior in vivo. Even though thymomas may have a benign appearance and a more indolent course, patients with a thymoma should undergo operative resection due to the potential for invasive spread or morbidity due to local mass effects. For most tumors, a complete resection results in long-term survival. Thus, the majority of thymic abnormalities are treated by surgical extirpation, and it is generally agreed that the excision should be complete. However, the surgical approach to facilitate a complete thymectomy has been a matter of considerable controversy.

MG is a condition characterized by abnormal fatigue of muscles, which worsens as the day progresses, and is relieved by rest. This may be isolated to ocular symptoms, or involve generalized limb weakness. MG is believed to be an autoimmune disease caused by antibodies to acetylcholine receptors at the neuromuscular junction, induced by thymic epitopes. Thymectomy for MG was first described by Blalock, who reported a case of a patient with thymoma who also had MG.² Interestingly, he performed this procedure through a partial upper sternotomy, T-ed off at the right third intercostal space. Following resection, the patient noted marked improvement in myasthenic symptoms and was able to discontinue all anticholinergic medications. Since that time, numerous studies have detailed thymic resection for MG, with mostly positive, but variable results. Currently, patients are evaluated according the Osserman classification (Table 160-1).³ There is consensus that most patients with generalized MG as well as those with debilitating ocular symptoms not controlled by anticholinesterases should undergo thymectomy.^1,4,5 Many authors believe that intervention early in the course of disease (<2 years) also provides a more favorable outcome. However, not all thymic resections are equal in extent, and thus the type of resection performed remains a source of debate.

In most studies, 10% of patients with MG will have an associated thymic neoplasm, which may be identified preoperatively or incidentally in the resected specimen. About 40% of patients with a thymic neoplasm will have MG. Patients without thymoma are more likely to experience an improvement in myasthenic symptoms than those with thymoma.⁶

The presence of ectopic thymic tissue throughout the mediastinum and the problem in differentiating thymus from surrounding fat have led to significant controversy regarding the amount of thymic tissue to be resected and the areas to be explored. Although there is agreement that thymectomy should be complete, the definition is inexact and a multitude of procedures from maximally to minimally invasive have been proposed. Noting the extensive and variable position of extracapsular thymic tissue (see Fig. 160-1), Jaretzski and Wolf⁷ described the combined cervical and transsternal approach for maximal removal of all thymic tissue, including potential thymic rests. Cooper et al.⁸ described the transcervical thymectomy which removed the bulk of the gland. Other minimally invasive approaches, including video-assisted thoracoscopic surgery (VATS) and robotically assisted surgery, have also been described. The outcomes of these procedures appear to be fairly comparable, although there are no clinical trials directly comparing these procedures and patient selection may bias the results. The transsternal thymectomy is a reasonable approach, providing less morbidity than the combined approach, while offering the exposure necessary to remove almost all thymic tissue, even in the cervical region and in the most inferior portions of the mediastinum. Sternotomy is generally well tolerated with patients ambulating almost immediately and having a hospital stay of approximately 3 days.

Thymoma

Patients usually come to medical attention because of cough or nonspecific chest pain. Many patients are asymptomatic and are identified by the finding of a widened mediastinum on a routine chest x-ray. Chest CT readily identifies the lesion in the thymus. Usually the diagnosis is clear and biopsy is not necessary. Characteristically the lesion has a uniform density and may be lobulated. Masses that are associated with significant mediastinal adenopathy are more likely to be lymphoma and a biopsy may be necessary to distinguish the two. Other anterior mediastinal masses include thyroid, which may be identified by close association with one or both thyroid lobes, and germ cell tumors which are often more heterogeneous. The tumor markers α-fetoprotein and β-HCG may be obtained if a nonseminomatous germ cell tumor is suspected.

All patients with thymic neoplasms are candidates for resection. The chest CT should be reviewed carefully to determine the location and extent of disease. There is sufficient evidence to indicate that completeness of the resection is the most important prognostic factor for most stages of the disease.⁹ The staging system most commonly used is the Masaoka–Koga system (Table 160-2) in which staging is determined by the degree of invasion of the capsule and surrounding structures.¹⁰ Stages I and II are treated with operation. For patients with Stage III disease, if a complete resection is anticipated, then surgery is employed.⁹ If not, the patients are treated with preoperative chemotherapy followed by surgery.⁹ To ensure complete resection, especially in Stage III, the transsternal approach is advocated. Minimally invasive approaches have been proposed, and may be suitable for smaller, lower stage tumors. However, as the overall outcome of thymoma resection is measured by 10-year survival rates, a long period of follow-up will be required to assess the oncologic efficacy of such procedures.

Myasthenia Gravis

Patients with MG are most often under the care of a neurologist and are managed with anticholinergics such as pyridostigmine bromide (Mestinon®), often accompanied by steroids (prednisone). Other immunosuppressants such as azathioprine and mycophenolate mofetil may be used in some patients. Once a candidate is identified, every effort should be made to minimize immunosuppressants, especially steroids, prior to surgery, while maintaining acceptable control of symptoms. Intravenous immunoglobulin (IVIG) may be administered in the preoperative period to help optimize patients. As respiratory complications are common in these patients, pulmonary function tests are useful. A chest CT is indicated because of the incidence of associated thymoma. For those patients who present with overwhelming MG symptoms and respiratory compromise (myasthenic crisis), ventilator support with additional immunosuppressants and plasmapheresis may be required to optimize patients. Such individuals are at highest risk for postoperative morbidity and mortality.

When performing a thymectomy for MG, the perioperative strategy must be a collaborative effort between the respiratory therapists, primary care physician, neurologist, anesthesiologist, intensivist, and surgeon. The problems associated with postoperative care can be directly correlated to the severity of symptoms at the time of operation.¹¹ Unless patients require preoperative parenteral steroids, hemodynamic stabilization, or plasmapheresis, they can be admitted to the hospital on the day of surgery. In general, anticholinesterase agents (pyridostigmine bromide) should be discontinued 8 hours prior to operation. Discontinuing these medications any earlier, especially in patients with severe myasthenia, can result in a myasthenic crisis, whereas continuing the medications, particularly in patients with mild symptoms, can result in a postoperative cholinergic crisis. In severe cases, an additional intramuscular injection of a small dose of pyridostigmine bromide can be administered just before the operation. Alternatively a continuous infusion of neostigmine may be used in severe cases (total daily dose = total daily dose of pyridostigmine bromide divided by 60).¹² If the patient is on steroids or has received them in the previous few months, perioperative parenteral steroid coverage is provided, beginning with 100 mg of hydrocortisone 1 hour before surgery and continuing every 8 hours for the first 24 hours, then tapered to the preoperative dose. Perioperative antibiotics are administered within 1 hour of the procedure. Usually a first-generation cephalosporin (e.g., cefazolin) suffices. Aminoglycoside antibiotics are contraindicated because they increase the neuromuscular block.

Technique

Anesthesia

A thoracic epidural catheter is often useful for postoperative analgesia. General anesthesia can be performed safely with selective use of agents that do not potentiate the neuromuscular defect. Chemical paralysis is not required for sternotomy. Neuromuscular blocking agents, especially competitive (nondepolarizing) agents should be avoided because of the long-lasting adverse effects on myasthenic patients. Myasthenic patients are very sensitive to the administration of nondepolarizing agents which could result in prolonged postoperative respiratory failure. If needed for intubation, a small dose of a noncompetitive depolarizing agent (succinylcholine) may be used.