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Video-assisted Transcervical Thymectomy

      Myasthenia gravis (MG) is an autoimmune disorder diagnosed clinically for the first time at the end of the 17th century. Intense research into the pathogenesis of the disease has led to the discovery of an antibody directed against the muscle nicotinic acetylcholine receptor (AchR) in 1973 and, more recently, to the finding of a new antibody directed against the muscle-specific receptor tyrosine kinase (MuSK) in a subgroup of patients that remain seronegative for AchR antibodies.
      • Hoch W.
      • McConville J.
      • Helms S.
      • et al.
      Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies.
      Blalock’s initial experience in the early 1940s and subsequently published series of surgically treated patients led to the widespread acceptance of thymectomy in the treatment of MG despite the absence of a prospective randomized trial comparing surgery with medical treatment alone.
      • Drachman D.B.
      Myasthenia gravis.
      Controversies remain, however, with regard to the timing and extent of surgery to be performed. Some authors recommend thymectomy early in the course of the disease, whereas others reserve surgery for when medical therapy fails or if a thymoma is suspected. Different surgical approaches have been recommended including transcervical, transsternal, and more recently a transthoracic thoracoscopic thymectomy. All procedures allow extracapsular resection of the thymus and vary somewhat in the extent of mediastinal fat removal, which may contain foci of thymic tissue. The most extensive resection combines the transcervical and transsternal thymectomy procedures and includes removal of all mediastinal fatty tissue, both sheets of mediastinal pleura along with a sharp dissection of the pericardium.
      The transcervical approach was first described in the late 19th century for thymic enlargement in children and consisted of an enucleation of the thymus from within its capsule. Although initially reported in an adult patient with MG by Sauerbruch in 1912, the transcervical approach was modified to completely remove the thymus with its capsule and reintroduced in the 1960s for patients with MG. Through this approach, Kark and his colleagues reported fewer postoperative complications when compared with the transsternal approach.
      • Kark A.E.
      • Kirschner P.A.
      Total thymectomy by the transcervical approach.
      Consequently, their patients were operated on earlier in the course of the disease and were shown to have more rapid rate of improvement.
      To improve exposure and to facilitate removal of the thymic gland and extracapsular thymic tissue through the neck, Cooper and colleagues described the use of a special right-angle manubrial retractor to elevate the sternum (Cooper retractor, Pilling Company, Fort Washington, PA). Using the same retractor, we observed that the routine use of a video-thoracoscope introduced through the cervicotomy further improves visualization of the mediastinum and permits teaching of the technique under direct supervision.
      • de Perrot M.
      • Bril V.
      • McRae K.
      • et al.
      Impact of minimally invasive transcervical thymectomy on outcome in patients with myasthenia gravis.
      Currently, the combination of early surgical referral, optimization of medical status when necessary by plasmapheresis, video-assisted transcervical thymectomy, and careful perioperative management have led to optimized care for patients with MG.

      Preoperative Care

      All patients with a diagnosis of MG are referred for surgery unless they are over 50 years of age and/or experience only ocular symptoms, in which case the decision to proceed with surgery is decided on a case-by-case basis.
      All patients have computed tomography (CT) scan of the thorax before surgery to exclude a thymoma. If a thymoma is detected, a transsternal approach is always chosen. Relative contraindications to a transcervical approach include prior cervico-mediastinal surgery and/or radiation, and cervical spine pathology limiting extension of the neck. Age, gender, obesity, and exposure to steroids were not considered contraindications to the transcervical approach.
      There is no role for urgent thymectomy in patients with myasthenic crisis as immediate clinical improvement postoperatively should not be expected. Rather, a period of 3 to 12 months is most often observed before clinical improvement can be seen following thymectomy. Furthermore, surgery in the setting of myasthenic crisis predisposes the patient to a significantly increased risk of postoperative respiratory failure.

      Operative Technique

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      Figure 1Surgery is performed in the supine position. Patients are intubated with a single lumen endotracheal tube. The neck is extended and an inflatable pillow is placed beneath the patient transversely, at the level of the scapulae, to permit further hyperextension of the neck. The neck and full chest is prepped in case a sternotomy is required.
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      Figure 2A curvilinear incision is made in the skin at the base of the neck, one finger breadth above the sternal notch, and extended on each side to the medial border of the sternocleidomastoid muscle. The incision is extended through the platysma muscle and flaps are developed superiorly to the level of the inferior aspect of the thyroid cartilage and inferiorly to the sternal notch. The interclavicular ligament is divided.
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      Figure 3The strap muscles are then split vertically in the midline and elevated bilaterally to expose the superior poles of the thymus gland, which lie opposed to the posterior surface of the sternothyroid muscles. It is imperative that this be done using careful sharp dissection with meticulous attention to control of small blood vessels with electrocautery. A bloodless field makes it significantly easier to delineate the upper poles of the thymus gland from fatty tissue in the neck. Each superior pole of the gland is mobilized near the inferior thyroid vein.
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      Figure 4The upper pole is divided between ties at the point where the thymic tissue terminates.
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      Figure 5A heavy silk suture, cut long, is placed on each upper pole and used as a “traction” suture to facilitate retraction of the gland.
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      Figure 6The thymus gland is then followed inferiorly to the thoracic inlet using a combination of blunt and sharp dissection. The retrosternal space is cleared with blunt finger dissection. This dissection is immediately substernal and extends at least 5 to 8 cm to accommodate the placement of the Cooper retractor without tension on the thymus gland. If the dissection is not deep enough, the thymus will be pulled into the mediastinum by the retractor as it is inserted. The Upper Hand retractor (Poly-Tract, Pilling Company, Fort Washington, PA) is then set up with the Cooper Thymectomy retractor blade (Pilling Company), which is then placed beneath the sternum to elevate it and open the thoracic inlet. The inflatable pillow that was placed at the start of the procedure is deflated at this point to further improve the thoracic inlet exposure. Care is taken to make sure that the patient’s head is not elevated off the operating table pillow by the sternal retraction. (Color version of figure is available online at http://www.us.elsevierhealth.com/optechstcvs.)
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      Figure 7The 30-degree videothoracoscope is then placed at the right lateral aspect of the neck incision to provide light for direct operating and a video magnified view of the operating field on a monitor for the surgeon and assistants. Pressure is maintained laterally with the thoracoscope to keep the telescope out of the line of sight of the operating surgeon as much as possible.
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      Figure 8The dissection of the gland is carried down into the thorax using primarily blunt dissection. The thymic veins draining into the innominate vein are identified posteriorly and divided between stainless steel clips. Two clips are placed on the innominate vein side. The arterial vessels entering the gland laterally from the internal mammary arteries are also clipped with stainless steel clips. The ventilatory tidal volume and rate are frequently reduced to facilitate exposure in the mediastinum.
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      Figure 9The dissection is carried down along the pleura to the inferior poles of the gland alternatively on both sides. A dissecting “peanut” on a curved Swedish-Debakey dissector is used to sweep each inferior pole up.
      Figure thumbnail gr10
      Figure 10The dissector is placed on the pericardium, distal to the inferior pole of the thymus gland, and in a sweeping motion the gland is extracted from the inferior mediastinum. After this maneuver, the “socket” in which the inferior pole of the gland resided is clearly visible, as is the underlying pericardium. This technique can be done under direct vision with the light of the thoracoscope as an aid; or surgeons comfortable with thoracoscopic operating can operate using the thoracoscopic images on the monitor to perform the operation. The assistance of the videothoracoscope routinely provides good visualization of the lower mediastinum, down to the diaphragm if necessary. On occasion, when it is impossible to complete the operation through the transcervical route using direct vision only, the videothoracoscope can enable successful completion of a thymectomy without having to convert to a sternotomy.
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      Figure 11Once the gland is excised, if there is any further mediastinal fatty tissue present that is suspicious for being thymic tissue, this is excised or biopsied for frozen section analysis to ensure that no residual thymic tissue is left behind. A #7 Jackson-Pratt (JP) drain (Zimmer, Dover, OH) is inserted through a lateral stab wound in the neck, placed down into the mediastinum and the manubrial retractor is removed. The strap muscles are approximated with a single figure of eight vicryl suture (Davis & Geck, Danbury, CT) and the platysma is closed with a running 3-0 vicryl suture. The skin is closed with a running 4-0 vicryl subcuticular suture. If it is felt that a total thymectomy can not be safely completed through the transcervical route, the operation is converted to a partial upper sternotomy. This is performed by the addition of a vertical incision extending down from the cervical incision to just below the manubrium. The incision in the sternal bone is then “J’d” out into the third or fourth intercostal space with the oscillating saw, to create a partial upper sternotomy, which provides sufficient exposure to easily complete the operation. (Color version of figure is available online at http://www.us.elsevierhealth.com/optechstcvs.)

      Perioperative Management

      Anesthetic assessment is performed at an ambulatory preadmission clinic visit. Patients are admitted on the day of surgery. They either take their morning dose of pyridostigmine as usually scheduled or take it immediately before surgery. If surgery is delayed or scheduled for the afternoon, another dose of pyridostigmine is given before surgery. No other premedication is administered. Anesthesia is induced with propofol and fentanyl, and is maintained with isoflurane and nitrous oxide. Propofol is used in addition to inhaled anesthetics for maintenance of anesthesia in many patients. Muscle relaxation is rarely required. A short acting agent such as atracurium or rocuronium is used at reduced doses in less than 20% of cases. Patients are routinely extubated at the end of surgery in the operating room or occasionally in the recovery room.

      Postoperative Care

      Analgesia is given orally using acetaminophen with or without codeine; morphine is rarely required. Oral pyridostigmine at the patient’s usual dose is reintroduced 4 to 6 hours after surgery. If patients are on steroid therapy before surgery, an intravenous dose is given preoperatively and oral steroids are continued the next morning. Patients are ready to be discharged the next day after removal of the JP drain if their symptoms are stable and pain is controlled.

      Comments

      A total of 120 consecutive patients underwent transcervical thymectomy between January 1991 and December 2000 in our institution. There were 86 females with a median age of 33 years (range, 14-79) and 34 males with a median age of 36 years (range, 12-68). Time elapsed between onset of symptoms and thymectomy varied from 2 months to 17 years (mean, 25 ± 40 months). The mean preoperative Osserman grade was 2.7 ± 0.9 (range, 1-4). A total of 78 patients were treated with pyridostigmine only. Plasmapheresis was performed in 30 patients and intravenous immunogloblulin was administered to 3 patients before surgery.
      Surgery was converted to an upper sternotomy in 23 cases (19%). Poor exposure was cited in 17 cases, a mass suggesting a thymoma in 4 cases, and previous neck surgery with adherent tissue in 2 cases. The risk of conversion was significantly higher in males than in females and in patients with thymic involution rather than hyperplasia. The rate of conversion decreased from 22% in 1991 to 1994 to 9% in 1999 to 2000 (P = .4). During the same period, the proportion of patients treated without immunosuppression before surgery increased from 69% in 1991 to 1994 to 95% in 1999 to 2000 (P = .7), and the time elapsed between the onset of MG symptoms and thymectomy decreased from 30 ± 48 months in 1991 to 1994 to 14 ± 14 months in 1999 to 2000 (P = .3).
      Postoperative complications occurred in 4 patients. Two patients who required conversion to a sternotomy experienced myasthenic crisis and were intubated during the postoperative course. One patient had a hemothorax and one had a pneumothorax after the transcervical approach, and both patients were treated conservatively. No postoperative death occurred. Among patients with an uncomplicated course (i.e., excluding the 4 patients above), the median postoperative hospital stay was 2 days (range, 1-8 days) after transcervical thymectomy, and 3.5 days (range, 2-8 days) after conversion to an upper sternotomy (P < .0001). Following the transcervical approach, the median postoperative hospital stay decreased from 2 days (range, 1-8 days) before 1994 to 1 day (range, 1-8 days) thereafter (P = .0001). In contrast, the postoperative hospital stay after conversion to an upper sternotomy did not significantly change over time.
      On pathologic examination, the thymus was involuted in 60 cases, hyperplastic in 55 cases, and contained an incidental thymoma in 5 cases. All 5 thymomas remained undetected on the preoperative CT scan and were discovered at the time of surgery only. Three of them required conversion to a sternotomy, whereas two small (1 cm), encapsulated thymomas located in the upper part of the thymus could be safely removed through the transcervical approach. All 5 patients are alive without recurrence after 39 to 111 months (median 97 months). The proportion of thymic involution was significantly higher among patients treated with steroids before surgery than among those not taking steroids (38% vs. 16%, respectively; P = .01).
      One hundred patients were available for complete follow-up. Ten patients were lost to follow-up and 10 have been followed for less than 6 months and were not included in the outcome analysis. After a median follow-up of 48 months (range, 6-117 months), 41% of the patients were in complete remission and 9% were in remission. The improvement in Osserman grade was not different between patients whose thymectomy was completed via the transcervical approach and those who required conversion to an upper sternotomy. Two patients presented with persistent myasthenic symptoms refractory to medical treatment and underwent re-exploration through a sternotomy 25 and 42 months after the transcervical approach despite the absence of residual thymic tissue on chest CT scan. One had thymic tissue in the anterior mediastinum discovered during the second surgery and subsequently became asymptomatic, whereas the other had no residual thymic tissue.
      Life table analysis showed that 91% of the patients were in complete remission at 10 years. Stratification according to gender, age at surgery (cut-off value of 34 years), latency of surgery (cut-off value of 10 months), preoperative Osserman grade (stages I-II vs. III-IV), and pathological findings (involution versus hyperplasia) showed no significant differences at 10 years. Further stratification of age (≤ 40, 41-60, and >60 years), latency of surgery (≤8, 9-12, >12 months), and preoperative Osserman grade (stages I, II, III, IV) also showed no significant differences (P = .5, P = .2, and P = .9, respectively). Stratification according to the need for preoperative immunosuppressive therapy showed no significant difference at 10 years when compared with patients receiving only pyridostigmine before surgery (P = .1). However, complete remission was achieved more rapidly in the group of patients treated without preoperative immunosuppression, reaching statistically significant differences after 5 years of follow-up (P = .04).

      Conclusions

      In conclusion, considerable improvement has been made since the time when only selected patients with severe MG unresponsive to medical therapy underwent thymectomy. Currently, transcervical thymectomy requires hospitalization for less than 24 hours in the majority of cases and is associated with very little morbidity. Patients therefore tend to be referred earlier in the course of their disease when they are in a more stable clinical condition. In the long term, this approach achieved complete remission in 91% of the patients.

      References

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        • McConville J.
        • Helms S.
        • et al.
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        N Engl J Med. 1994; 330: 1797-1810
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        • Kirschner P.A.
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        Br J Surg. 1971; 58: 321-326
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