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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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies.