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Radical Transsternal Thymectomy

      Abnormalities of the thymus comprise more than half of the lesions found in the anterior mediastinal compartment in adults. Greater than 95% of the tumors of the thymus are thymomas that originate from thymic epithelial cells. They generally present as an incidental radiographic finding. They are of surgical importance both as isolated entities as well as in association with myasthenia gravis (MG). Surgical excision is the cornerstone of therapy for thymoma.
      • Nakahara K.
      • Ohno K.
      • Hashimoto J.
      • et al.
      Thymoma results with surgical resection and adjuvant postoperative irradiation in 141 consecutive patients.
      In addition, thymectomy is an integral component of the management of myasthenia gravis.
      Ludwig Rehn performed the first thymic operation in 1896, a transcervical exothymopexy for a patient with an enlarged thymus causing episodes of suffocation.
      • Rehn L.
      Compression from the thymus gland and resultant death. Excerpts from the transactions of the German Congress of Surgery, April 1906.
      He pulled the enlarged thymus out of the mediastinum and performed a pexy of the thymic capsule to the posterior aspect of the manubrium. Transcervical thymic surgery was generally the preferred route until the 1930s. In 1936, Dr. Alfred Blalock performed the first successful transsternal thymectomy through an upper median sternotomy in a patient with myasthenia gravis and a large anterior superior mediastinal tumor.
      • Blalock A.
      • Mason M.F.
      • Morgan H.J.
      • et al.
      Myasthenia gravis and tumors of the thymic region.
      Radical transsternal resection evolved from this approach and the surgical technique now focuses on the en bloc resection of the entire thymus and pericardial fat pad from the thyroid gland down to the diaphragm and laterally to the phrenic nerves. This is performed through a full sternotomy. Advantages of this approach are direct and safe access to the entire anterior mediastinum. Opening the pleural spaces allows visualization and preservation of the phrenic nerves. Advocates of this approach feel that radical resection is the technique that is most likely to remove all thymic tissue and give the highest likelihood of cure, particularly in the setting of myasthenia gravis.
      • Masoaka A.
      • Yamakawa Y.
      • Niva H.
      • et al.
      Extended thymectomy for myasthenia gravis patients a 20 year review.
      • Roth T.
      • Ackermann R.
      • Stein R.
      • et al.
      Thirteen years follow-up after radical transsternal thymectomy for myasthenia gravis. Do short-term results predict long-term outcome?.
      They point to the fact that even small portions of remnant thymic tissue has been associated with recurrent myasthenic symptoms and that reoperation after transcervical thymectomy has been required for resection of remnant tissue.
      • Masaoka A.
      • Monden Y.
      • Seike Y.
      • et al.
      Reoperation after transcervical thymectomy for myasthenia gravis.
      The three most commonly cited indications for thymectomy are the following: (1) thymic hyperplasia associated with myasthenia gravis
      • Jaretzki 3rd, A.
      • Bethea M.
      • Wolff M.
      • et al.
      A rational approach to total thymectomy in the treatment of myasthenia gravis.
      ; (2) encapsulated or invasive thymomas
      • Detterbeck F.C.
      • Parsons A.M.
      Thymic tumors.
      ; and (3) thymic carcinomas.
      • Greene M.A.
      • Malias M.A.
      Aggressive multimodality treatment of invasive thymic carcinoma.
      Thymic hyperplasia is generalized enlargement of the thymic gland caused by diffuse thymocyte proliferation. Thymic hyperplasia is an immunologic condition.
      • Beeson D.
      • Bond A.P.
      • Corlett L.
      • et al.
      Thymus, thymoma, and specific T cells in myasthenia gravis.
      In children, thymic hyperplasia can be associated with a variety of endocrine disorders including hyperthyroidism. In adults, thymic hyperplasia has been associated with thymoma as well as many immune dysfunction syndromes—the most notable being myasthenia gravis. Removal of the thymus gland, by a variety of surgical approaches, appears to influence the immune dysfunction observed in myasthenia gravis.
      • Jaretzki 3rd, A.
      • Bethea M.
      • Wolff M.
      • et al.
      A rational approach to total thymectomy in the treatment of myasthenia gravis.
      The mechanism of this influence, and the relative benefit of removing all residual or ectopic thymic tissue, is unclear.
      The most frequent asymptomatic indication for thymectomy is thymoma. Chest CT scan imaging of the thymus gland is often diagnostic of a thymic mass because the thymus gland is the only anatomic structure anterior to the brachiocephalic vein. Thymomas are not associated with lymphadenopathy. The presence of a separate aortopulmonary window mass or paratracheal adenopathy should raise the possibility of lymphoma. Similarly, Hodgkin’s disease can be associated with thymic enlargement.
      • Wernecke K.
      • Vassallo P.
      • Rutsch F.
      • et al.
      Thymic involvement in Hodgkin disease CT and sonographic findings.
      In most cases, the radiographic appearance of thymoma is sufficient to preclude the necessity of a tissue biopsy before surgical resection. Further, tissue biopsy is notoriously inefficient because of the marked heterogeneity within the thymus gland. It is common for a resected thymoma to reflect areas of lymphocyte predominance (stage I) and epithelial predominance (stage III) within the same tumor.
      • Detterbeck F.C.
      • Parsons A.M.
      Thymic tumors.
      • Loehrer Sr, P.J.
      • Wick M.R.
      Thymic malignancies.
      Although the subsequent development of pleural implants is commonly attributable to presurgical biopsy, the supportive data are weak. Pleural implants clearly occur without prior biopsy. Similarly, needle or mediastinotomy biopsy is infrequently associated with localized pleural disease. Local incisional recurrence has rarely been reported.
      Thymic carcinomas are rare epithelioid malignancies. Thymic carcinomas are frequently aggressive tumors that spread both within the pleural space (so-called “drop” metastases) as well as hematogenously. In most cases, the diagnosis is suspected on the radiographic studies and confirmed by anterior mediastinotomy. These tumors should be treated with aggressive combination therapy.
      • Greene M.A.
      • Malias M.A.
      Aggressive multimodality treatment of invasive thymic carcinoma.
      Combined neoadjuvant chemoradiation therapy followed by aggressive radical surgery has had only a limited impact on patient survival.

      Operative Technique

      Figure thumbnail gr1
      Figure 1The thymus gland is derived from the 3rd pharyngeal pouch. The primordia of the thymus gland arises just ventral to the inferior parathyroid gland. The primordial thymic lobes descend caudally and fuse in the midline.
      • Gilmour J.R.
      Some developmental anomalies of the thymus and parathyroids.
      Ectopic thymus gland can be found along the course of this descent as well as in relation to the parathyroid gland.
      • van Dyke J.H.
      On the origin of accessory thymus tissue, thymus IV The occurrence in man.
      The most common sites of ectopic or variant thymic tissue are (1) indistinct extensions within mediastinal fat (90%)
      • Morin A.
      • Riou R.J.
      • Fischer L.
      Various aspects of vascularization of the thymus, its vestiges and of the thymic capsule.
      ; (2) extensions lateral to the phrenic nerves (70%)
      • Jaretzki 3rd, A.
      • Bethea M.
      • Wolff M.
      • et al.
      A rational approach to total thymectomy in the treatment of myasthenia gravis.
      ; (3) extensions into the aortopulmonary window (25%)
      • Jaretzki 3rd, A.
      • Bethea M.
      • Wolff M.
      • et al.
      A rational approach to total thymectomy in the treatment of myasthenia gravis.
      ; and (4) ectopic thymus in the cervical fat (20%).
      • Maisel H.
      • Yoshihara H.
      • Waggoner D.
      The cervical thymus.
      • Lewis M.R.
      Persistence of the thymus in the cervical area.
      Rarely, thymic tissue can be found in a retrothyroid position or posterior to the brachiocephalic vein.
      • Jaretzki 3rd, A.
      • Bethea M.
      • Wolff M.
      • et al.
      A rational approach to total thymectomy in the treatment of myasthenia gravis.
      Figure thumbnail gr2
      Figure 2For anesthetic management, we recommend placement of a double-lumen endotracheal tube for sequential lung isolation. The skin incision for a radical thymectomy can be cosmetically located in the midline. The length of the incision is typically 8 cm, about half the length of the adult sternum (17 to 18 cm). Before sternotomy, skin flaps are mobilized circumferentially. The full-thickness skin flaps are raised superficial to the pectoralis fascia. Perforating vessels are controlled by electrocautery. The mobility of the skin flaps permit comfortable access to the suprasternal notch and the manubrium with the appropriate retraction.
      Figure thumbnail gr3
      Figure 3Retraction of the skin flaps permits a full sternotomy to be performed. The sternotomy facilitates exposure to the inferior mediastinal and cervical fat. A sternal retractor, initially placed in the midline, is moved to facilitate exposure in the appropriate dissection areas.
      Figure thumbnail gr4
      Figure 4The thymic dissection begins in visible areas of midline pericardium. The dissection is carried cephalad along the pericardium toward the brachiocephalic vein. The dissection is performed with two dental pledgets (cylindrical dental tampon) held by a needle-nosed 11-inch ring handled instrument (Frazier clamp). The cylindrical pledgets facilitate dissection of the pericardial plane while being sensitive to tumor invasion or significant adhesions to the pericardium The dissection is completed at the inferior boarder of the brachiocephalic vein. The intervening tissue is the de facto thymic isthmus and is encircled with an umbilical tape. The capsule of the midline thymus is often indistinct. In addition, the midline is a frequent area of ectopic or discontinuous foci of thymic tissue. For these reasons, the entire anterior mediastinal soft tissue from the anterior pericardium to the retrosternal space is included in the specimen. Dissection of the inferior boarder of the brachiocephalic vein invariably reveals the thymic vein near the midline. This vein is transected between silk ties.
      Figure thumbnail gr5
      Figure 5The right-sided dissection begins at the retrosternal pleura and continues posterior to the superior vena cava and right atrium. The pleura is incised to facilitate visualization of the phrenic nerve. In most cases, the pleura is incorporated into the thymic specimen because of adhesions between the thymic gland. The pleura can be left intact if the mediastinal fat and thymic lobe are readily separable from the gland and mediastinal fat and the phrenic nerves have been identified.
      Figure thumbnail gr6
      Figure 6The cervical extent of the thymic lobe is dissected bluntly using dental pledgets to facilitate the separation of the thymic horn from the surrounding tissue. The cervical extent of the thymic horn lies medial to the carotid artery and deep to the strap muscles. Surrounding fat should be included in the dissection because of the likelihood of ectopic or accessory thymic tissue.
      • Maisel H.
      • Yoshihara H.
      • Waggoner D.
      The cervical thymus.
      During the course of this dissection, arterial blood supply from the internal thoracic artery or inferior thyroid artery may be encountered.
      • Bell R.H.
      • Knapp B.I.
      • Anson B.J.
      • et al.
      Form, size, blood supply and relations of the adult thymus.
      These branches should be clipped and divided.
      Figure thumbnail gr7
      Figure 7The superior horn of the thymus gland is identified above the thoracic inlet. The cephalad extension of the thymus to the level of the thyroid gland likely reflects its embryologic descent. A leash of small vessels, typically from the inferior thyroid artery, is clipped. The clips provide hemostasis as well as a radiographic marker of the extent of the dissection. The cephalad horn of the thymus is marked with a silk tie and a mosquito clamp. The mosquito is useful because the weight of the instrument is sufficient for retraction without disrupting the delicate cervical extension of the lobe. A similar dissection is performed on the left side. There is no attempt to identify retrothyroid thymic tissue.
      Figure thumbnail gr8
      Figure 8The inferior extent of the dissection encompasses mediastinal fat from the retrosternal space to the phrenic nerve. The pleura is rarely involved at this level. If adhesions to the pleura or lung are present, the tissue is resected en bloc. The dissection is extended from phrenic nerve to phrenic nerve. Care is taken to avoid injury to the phrenic nerve. Electrocautery is used sparingly. The arterial blood supply arises from the pericardiacophrenic artery bilaterally.
      • Bell R.H.
      • Knapp B.I.
      • Anson B.J.
      • et al.
      Form, size, blood supply and relations of the adult thymus.
      Figure thumbnail gr9
      Figure 9The aortopulmonary (AP) window extension of the thymus is only partially visualized from a median sternotomy. Particularly in AP window thymomas, we commonly use complementary thoracoscopic imaging to facilitate an assessment of hilar involvement. Occasionally, large AP window tumors cannot be adequately resected using a median sternotomy. In these cases, we use a hemi-sternotomy combined with an anterior thoracotomy in the 3rd or 4th intercostal space (hemi-clamshell incision). The AP window thymic neoplasms are the most frequent site of phrenic nerve involvement. Tumor involvement of the phrenic nerve requires division of the nerve. If the phrenic nerve is resected, consideration should be given to immediate plication of the diaphragm to limit discoordinate respiratory movement (pendeluft) in the postoperative period. Plication of the central tendon of the diaphragm is particularly important in patients with compromised preoperative lung function.
      Figure thumbnail gr10
      Figure 10The dotted lines represent the boundaries of the radical, en bloc transsternal resection.
      Figure thumbnail gr11
      Figure 11The incision is drained using two 19 FR Blake drains. One drain is placed in the anterior mediastinum. Occasionally, when a pulmonary resection has been performed as part of the en bloc resection, a separate shortened Blake drain is placed in the pleural space. The sternum is closed using five sternal wires; two wires are placed in the manubrium. A superficial Blake drain is placed beneath the skin flaps to prevent a hematoma from developing in the subcutaneous space. The drains are placed on active suction overnight and usually removed the next morning. Patients are typically discharged from the hospital on postoperative day 3.

      Conclusion

      In the absence of lymphadenopathy, mediastinal invasion, or anatomic ambiguity, we recommend transsternal total thymectomy of a thymoma without prior biopsy. The transsternal approach can be performed with a cosmetically acceptable incision. The superficial skin incision of 7 to 8 cm is comparable to the aggregate incision of a thoracoscopic approach and the sternotomy is well tolerated by most patients. More importantly, the transsternal approach provides sufficient incision and exposure to extract the tumor intact for detailed pathologic evaluation of the thymic capsule and to adequately assess for any local invasion. We feel that this approach provides exposure of the neck and anterior mediastinum that is superior to a transcervical approach. We recommend transsternal thymectomy for thymomas that may require a radical resection and for total resection of the observable thymus gland and associated ectopic thymic tissue.

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