158: Transcervical Thymectomy

Myasthenia gravis (MG) is an autoimmune disease mediated by anti-acetylcholine receptor antibodies (AChrab) directed against the acetylcholine receptor region of the post-synaptic membrane. Blocking and accelerated degradation of acetylcholine receptors lead to impaired neuromuscular transmission and muscle weakness.¹ MG has a predilection for the ocular and bulbar muscles, but generalized proximal muscle weakness is also common. Fatigable weakness is the hallmark of MG and the disorder is diagnosed by the clinical presentation, abnormal single-fiber electromyography, repetitive nerve stimulation tests, and elevated ACh and/or anti-MuSK antibodies. Abnormalities of the thymus gland are commonly found in these patients. Of MG patients, 10% to 15% have thymoma. Lymphoid thymic hyperplasia is present in about 70%² Significant data exist to support an immunopathological role of the thymus in the development of autoimmune MG.³

The beneficial role of surgery for patients with MG was first described before the middle of the past century.⁴ Further clinical reports of the benefits of the thymectomy led to the acceptance of this procedure for patients with generalized MG as a standard of practice. Nonetheless, controversies surrounding the role of thymectomy in the treatment of MG are abound in the literature. The role of thymectomy can be questioned because no randomized, controlled trials comparing the best medical therapy and surgery exist. The changes in intensive care unit (ICU) care, ventilatory support, and the introduction of immunosuppressive therapy also have improved the clinical course of this disease and outcomes. Furthermore, the debate persists because of patient selection and methods of analysis of results vary from center to center. Regardless, surgery is currently considered to increase the likelihood of improvement.⁵ Retrospective studies suggest that patients undergoing thymectomy have higher remission rates than those who are treated medically.⁶

In a review, the likelihood of improvement, defined as medication-free remission, asymptomatic on medication, or improved on medication, was two times higher among patients undergoing surgery compared to patients managed medically.⁵ The median improvement rates were total remission 25%, asymptomatic with medication 39%, and clinically improved 70%. The benefits of thymectomy are often delayed with 25% achieving remission in the first year, 40% by the end of the second year, and 55% in the third year.⁷ These results, however, suggest that other factors in addition to surgery may contribute significantly to the improvement observed after surgery. Currently, an international randomized multicenter study comparing transsternal thymectomy to medical treatment is enrolling patients. It appears that this study has had difficulty enrolling patients, with current evidence favoring thymectomy for generalized, nonthymomatous MG, and also by other less invasive routes.

The point of debate in the surgical treatment of MG has been the preferred surgical approach. Some centers recommend maximal thymectomy (the Jaretzki approach; transsternal + transcervical) to eliminate the gland and possible extra-anatomical thymic tissue as well,⁸ whereas other centers favor a standard transsternal approach, while others have adopted a minimally invasive transcervical thymectomy.^9,10 A more recent surgical innovation is the modification of this procedure with the introduction of video-assisted transcervical thymectomy.¹¹ During this era of minimally invasive video-assisted surgery, transthoracic thoracoscopic thymectomy has gained popularity, as well. Several variations of this approach exist including unilateral, bilateral, bilateral combined with cervical approach, and robotic. The last surgical innovation for surgical treatment of MG is the infrasternal, either thoracoscopic or mediastinoscopic approach for thymectomy.¹² All procedures allow extracapsular resection of thymus and vary somewhat in the extent of mediastinal fat removal, which may contain foci of thymic tissue. The types of thymectomy have not been compared directly in any randomized study. There is a school of thought which advocated that maximal thymectomy is preferred over more conservative approaches to theoretically achieve a more complete resection of thymic tissue.¹³ A combination of transcervical and transsternal approach was recommended to maximize the resection. The outcome data, however, do not support improved results with “maximal thymectomy” over more minimally invasive approaches. Furthermore, approaches that are more patient-friendly are more easily accepted by the patients and their neurologists. To understand the different surgical approaches and categorize the extent of resection of thymus and surrounding tissue, the Myasthenia Gravis Foundation of America (MGFA) has broadly classified varying surgical techniques based on the approach and the extent of surgical resection. The meta-analysis of 21 retrospective studies showing a positive benefit of thymectomy in patients with MG included all types of thymectomy approaches.⁵ Furthermore, relatively large case series have shown comparable remission and improvement rates in MG patients with different types of thymectomy.^10,11 Thus, it is not clear at all that more extensive thymectomy procedures are more effective. Statistical reshuffling of crude data from different study reports may show different outcomes for different surgical interventions, but this type of reanalysis in itself may produce flawed results and does not provide definitive evidence of the benefits of one surgical approach over another. Ideally, a randomized trial of the different approaches would need to be done. Currently, no such study is planned and there is no consensus on the optimal surgical approach. Without randomized comparative studies, the decision as to surgical approach must rest on the surgeon's individual experience and facility with each given procedure. The underlying principle for thymectomy for MG remains the same regardless of surgical approach: a safe and complete thymectomy.

All patients should have a CT scan of the thorax before surgery to exclude a thymoma. Although VATS seems to be a safe and feasible approach for early stage thymoma, this approach is controversial and the follow-up times are still short considering that pleural metastases can appear more than 10 years after surgery.¹⁴ Therefore, if a thymoma is present, the preferred surgical approach remains a sternotomy or partial upper sternotomy.

Although the current consensus is to use thymectomy for patients with nonthymomatous generalized myasthenia, the role of surgery in other patient groups is much more controversial. In younger patients with ocular MG we recommend surgery, although some clinicians still hesitate to recommend surgery for this group.¹⁵ An important area of debate is the upper age limit for thymectomy. Because older individuals have thymic atrophy rather than hyperplasia, the use of surgery in this group does not appear to have the same theoretical rationale as in younger patients. In addition, one may be concerned that complications of thymectomy are likely to be greater in older patients. This has to be considered, however, in the context of what can be achieved today with improved anesthesia and minimally invasive techniques for thymectomy. There are, in fact, retrospective studies reporting that thymectomy is safe in patients over age 60, and 16% of those patients over age 60 have thymic hyperplasia.¹⁶ Other retrospective series have shown that age does predict outcome in thymectomy for MG with lower response rates in older subjects.¹⁷ Considering the low morbidity of transcervical thymectomy in contrast to the morbidity of chronic immunosuppression in the elderly patient, we currently offer thymectomy to patients over 60 years of age. At the other age spectrum, thymectomy also is not generally recommended in very young children,¹⁸ although it is sometimes necessary in young teenagers with severe MG.

The surgical treatment of MG patients should ideally belong to a dedicated team consisting of a thoracic surgeon, anesthesiologist, and neurologist. After the confirmation of the diagnosis of MG, symptoms should be medically stabilized. Cholinesterase inhibitors are used as the first line of therapy. Prednisone and other immunosuppressive agents are available for the persistent symptoms. Steroids are avoided preoperatively, if possible, to avoid the adverse effects on wound healing and infections. Thymectomy is never an emergency, and therefore, the patient's strength and respiratory status should be optimized before the well-planned elective surgery. There is no role for urgent thymectomy in patients with myasthenic crisis, as immediate clinical improvement postoperatively should not be expected. Furthermore, surgery in the setting of myasthenic crisis predisposes the patient to a significantly increased risk of postoperative respiratory failure.¹⁹ The likelihood of prolonged mechanical ventilation is increased in patients with severe generalized weakness and/or with bulbar symptoms, as well. These patients should first be treated with plasmapheresis prior to surgery to optimize their condition. High-dose intravenous immunoglobulin (IVIg) is sometimes used as an alternative to plasmapheresis. Because of the short-lived benefits of these treatments, surgery should be planned in the following 2 to 3 weeks. It should be noted that surgery should not be performed before 5 days after plasmapheresis because of possible coagulation abnormalities related to the treatment. Over the years at the Toronto General Hospital, we have limited the administration of immunosuppressive therapy before surgery, and preoperative stabilization is most often accomplished with pyridostigmine with the addition of plasmapheresis for the higher-grade myasthenic patients only.

Preoperative anesthetic assessment is of importance. The stabilized state of disease can be confirmed just a couple of days before surgery allowing safe same day admission for surgery. Patients should take their morning dose of pyridostigmine as usually scheduled, ideally taken immediately prior to surgery. If surgery is delayed or scheduled for afternoon, another dose of pyridostigmine is given before surgery. No other premedication is administered. Anesthesia can be safely induced with propofol and fentanyl, and maintained with isoflurane and nitrous oxide. Propofol could be used in addition to inhaled anesthetics for maintenance of anesthesia. Muscle relaxation is rarely required. The aim is routine extubation at the end of surgery.

Transcervical thymectomy was the approach used for the earliest described thymectomies,²⁰ but was replaced by the transsternal approach by Blalock and his contemporaries midway through the past century.⁴ We prefer the video-assisted transcervical thymectomy (VTCT) approach for the treatment of nonthymomatous MG since, despite being a less invasive procedure, it gives excellent bilateral exposure of the thymus, including the lower poles, and permits complete thymectomy. Furthermore, unlike transthoracic video-assisted thymectomies, the transcervical route obviates entry into the pleural spaces, obviates the need for chest tubes, provides enhanced exposure in the neck region, and does not require split lung anesthesia via a double-lumen endotracheal tube.

Relative contraindications to a transcervical approach include prior cervicomediastinal surgery and/or radiation, and cervical spine pathology limiting extension of the neck. Surgery is performed in the supine position with an inflatable bag under the shoulders. The bag is inflated to provide good neck extension. Both arms are tucked in at the sides. The neck and full anterior chest is prepped in case a sternotomy is required. A 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 sternocleidomastoid muscle (Fig. 158-1). This incision is extended through the skin and platysma muscle. Flaps are then developed superiorly to the level of the inferior aspect of the thyroid cartilage and inferiorly to the sternal notch. The 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 thymic tissue from fatty tissue in the neck. Each superior pole of the gland is mobilized near the inferior thyroid vein. The upper pole is divided between ties at the point where the thymic tissue terminates. A heavy silk suture, cut long, is placed on each upper pole and used as a “traction” suture to facilitate orientation and traction of the gland (Fig. 158-2). The superior poles are dissected and pulled up, and the capsule of thymus gland is followed inferiorly to the thoracic inlet.

The retrosternal (retromanubrial) space is cleared to accommodate the placement of the Cooper retractor.⁹ The Cooper retractor blade is placed beneath the manubrium to elevate it and open the thoracic inlet (Fig. 158-2). 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 by the sternal retractor.

We use a 5-mm 30-degree videothoracoscope 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 (Fig. 158-3). The dissection of the gland is carried down into the thorax using primarily blunt dissection. The arterial vessels entering the gland laterally from the internal thoracic artery branches are clipped with stainless steel clips. The thymic veins (there are often several), which drain into the innominate vein, are identified posteriorly and divided between stainless steel clips. The assistance of the videothoracoscope provides good visualization of the lower mediastinum, down to diaphragm if necessary. The ventilation rate and tidal volume can both be decreased to facilitate exposure in the mediastinum. The dissection of the gland is carried down alternately on both sides until the inferior poles of the gland are clearly identified and a dissecting “peanut” on a long-curved Swedish-Debakey dissector is used to sweep up each inferior pole. The 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. 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 Cooper retractor is removed. The strap muscles are approximated and the platysma and the skin are closed. Patients are discharged home on the morning after surgery.

In rare instances, if complete thymectomy cannot be performed by removing the thymus and its capsule, the operation is usually converted to a partial upper sternotomy. This is carried out by the addition of a vertical skin incision extending down from the sternal notch to the lower end of manubrium. The sternal bone incision is then extended laterally in the third intercostal space (in a “T”) with the oscillating saw to create a partial upper sternotomy, which provides sufficient exposure to easily complete the operation.

The patient's respiratory status and requirements for ventilatory support are, by far, the most salient issues in the postoperative period. With careful preoperative preparation of the MG patient, ventilatory issues are rarely a problem. Patients are extubated in the operating room. They are instructed to take their morning dose of anticholinesterase medication with a sip of water immediately preoperatively, to optimize their strength at the time of extubation. They are given an additional dose in the recovery room. With the minimally invasive approach, the need of postoperative analgesia can be limited to acetaminophen with mild narcotics such as codeine. Strong narcotics are rarely required. Oral pyridostigmine at the patient's usual dose is introduced 4 to 6 hours after surgery. If patients are on steroid therapy before surgery, an intravenous stress dose is given on induction and oral steroids are continued at the patient's usual dose the next morning. With minimally invasive approaches today, patients almost never need postoperative care in the ICU and are ready to be discharged early the next day.

Their medications are continued at the same dose as preoperatively. The medications are not altered until 1 month after surgery when they are seen by the surgeon and the neurologist. A period of 3 to 12 months is most often observed before clinical improvement can be seen following thymectomy.²¹ Some patients may get transiently worse postoperatively and it is this exacerbation of myasthenic symptoms, rather than surgical considerations, that is the usual reason to keep a patient in the hospital for longer than 1 day. If symptoms worsen, the medication regimen may have to be altered to include prednisone or azathioprine. An occasional patient may deteriorate considerably. These patients should be expediently treated with plasmapheresis to prevent deterioration to the point of requiring ventilatory support.

The rate of surgical complications is low, <2% in our series.¹⁰ These were hemothorax and pneumothorax treated successfully by conservative methods. Wound complications have been reported, as well. The rate of recurrent nerve lesions is zero. The reported conversion rate was close to 10% in the early experience and is now in the range of 1%.^10,22

Transcervical technique offers a minimally invasive surgical approach with a low complication rate, a good cosmetic result, and a short length of recovery for a complete thymectomy in MG. Patient acceptance with this less invasive technique is better leading to greater application of surgery earlier in the course of this disease.

Transcervical thymectomy is a useful surgical option for patients with thymic hyperplasia; typically, patients with MG. Transcervical thymectomy, however, is not an option for patients with large glands and most thymomas. Anatomically, the transcervical dissection is limited by the brachiocephalic vein posteriorly and the sternum anteriorly (the thymus gland is the only normal anatomic structure between these structures). Although video optics have improved visualization and broadened surgical indications, the risk of inadequate resection or local seeding precludes the use of transcervical thymectomy in the vast majority of patients with thymomas.