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44 Anterior mediastinal lesions
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to blepharoptosis and diplopia. Skeletal and bulbar muscles
gradually become affected, which is manifested by weakness
in the extremities, impaired chewing, dysarthria, and nasal
speech. The diagnosis is confirmed by a Tensilon test, singlefiber electromyography, and determination of acetylcholine
receptor antibody levels. All patients should have a chest radiogram with posteroanterior and lateral views, as well as a
computerized tomographic (CT) examination to determine
whether thymus enlargement or an associated thymoma is
present.
Preoperative treatment including steroid administration
or plasmapheresis has been recommended by several groups
to permit safer surgery, especially for patients with bulbar
symptoms. Our current preference, however, is to perform
the extended thymectomy first and then to provide steroid
pulse therapy only when mechanical ventilation becomes
mandatory. Oral medication with an anticholinesterase agent
should be continued up to 1 day before the operation.
ANESTHESIA FOR MYASTHENIA GRAVIS
Emotional stress can be a cause of myasthenic crisis; thus,
preoperative sedation may be given with due consideration of
the depressant effect on respiration. Anticholinergics such as
atropine sulfate or scopolamine may be given. Anesthesia is
induced by short-acting barbiturates and maintained with
N2O and volatile anesthetics, such as isoflurane and sevoflurane. In most cases, endotracheal intubation and muscle
relaxation during the operation can be achieved by deepening
of the level of general anesthesia and topical use of local anesthetics without muscle relaxants. Because of the wide variety
of muscle strength conditions among MG patients, however,
the use of muscle relaxants is sometimes indicated. Both succinylcholine chloride and nondepolarizing agents can be used
under strict monitoring with a nerve stimulator.
OPERATION FOR MYASTHENIA GRAVIS
Extended thymectomy
INCISION AND EXPLORATION
An extended thymectomy may be performed through a
1
partial median sternotomy. A vertical skin incision is
made from 2 cm beneath the sternal notch to 2 cm above the
lowest portion of the sternum. The sternum is then divided
carefully along the midline, using an electric saw, from the
sternal notch to the level of the fifth intercostal space. A small
sternal retractor is first positioned, and the sternum is opened
slowly to avoid fracture. Bleeding from the sternal periosteum is stopped, and the connective tissue covering the thymus gland is divided along the midline from the pericardium
to the neck. Further, the thymus is separated from the posterior surface of the connective tissue by a bilateral blunt dissection. Then, a standard-sized sternal retractor is substituted
for the small one. In young women, supramammary or inframammary skin incisions are favored because these incisions
leave a cosmetically acceptable scar.
Connective tissue
1
Operation for myasthenia gravis 45
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DISSECTION OF THE THYMUS IN ASSOCIATION WITH
ADIPOSE TISSUES
The lower pole of the gland is dissected from the anterior
2
aspect of the pericardium; the dissection starts at the
midline and moves toward the pleural space. The pleural
reflections on the thymus gland are gently pushed to the sides
by blunt dissection. Thus, the lower pole can be easily mobilized together with the surrounding adipose tissue.
Right lower pole
with adipose tissue
Right lower pole
with adipose tissue
Lung
Pericardium
2
3
Lung
The lower pole is held in place by a tissue forceps, and
3
mobilization is continued upward, until the small arterial
branch from the internal mammary artery is identified and
divided between the ligatures. This process is repeated on the
contralateral side.
By retraction of the upper end of the wound and dissection
from the surrounding connective tissue, the two upper poles
of the gland can be identified. A small arterial branch usually
enters the uppermost end; it can be caught in a clamp and ligated before the upper poles are finally freed.
46 Anterior mediastinal lesions
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The gland is then separated from the left
4a, b
thymic veins can be identified. These veins are divided
between the ligatures, and the thymus is removed.
The adipose tissues around the upper poles of the
thymus and both brachiocephalic veins, as well as those
on the pericardium, should be resected meticulously.
The borders of the resection are the diaphragm caudally, the thyroid orally, and the phrenic nerves laterally. After hemostasis is accomplished, a chest tube is
positioned in the anterior mediastinum. If the pleural
space has been entered, the tip of the chest tube may be
advanced into that pleural space. The sternum is repositioned with wire sutures, and the wound is closed in
layers.
brachiocephalic vein, and two or three
Right brachiocephalic vein
Right phrenic
nerve
Thymus
Left brachiocephalic vein
Thymic vein
4a
Brachiocephalic artery
Left brachiocephalic
vein
POSTOPERATIVE CARE FOR MYASTHENIA
GRAVIS
The decision as to when to extubate the patient is based
largely on the preoperative condition. A chest radiograph is
usually taken in the operating room before extubation. Most
patients, with or without mild symptoms, are extubated in
the operating room using routine criteria. A patient with
more severe MG presenting bulbar symptoms may spend one
night on a ventilator in the intensive care unit. The patient is
extubated the next morning after normal arterial blood gas
Superior vena cava
Left phrenic nerve
4b
data are confirmed under T-piece breathing. An anticholinesterase agent at half dose is usually restarted on postoperative day 2 or 3, and the dosage is adjusted by
observing the condition of the patient. The patient must be
watched carefully, as a deterioration of ventilatory status
may occur several days postoperatively. When the patient is
determined to need ventilatory support for a long
period, steroid pulse therapy is given. Sufficient nutrition
should be provided by total parenteral nutrition or intragastric tube feeding, depending on the attending physician’s
preference.
Anesthesia for thymoma 47
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OUTCOME FOR MYASTHENIA GRAVIS
In general, patients with nonthymomatous MG have a better
remission rate (RR) than those with thymomatous MG. At
our institution, the RR in patients with nonthymomatous
MG was found to continue to rise, even after 5 years (45.9%
at 5 years, 55.8% at 10 years, 68.4% at 15 years). The palliation rate (PR) was stable after 3 years (91.6% at 3 years, 92.3%
at 5 years, 95.2% at 10 years, and 98.2% at 15 years). In a
series reported by Mulder, the RR was 51% and the PR was
87%. The RR was 37.9% and the PR was 87.3% in a series
described by Maggi. Jaretzki et al. have advocated ‘maximal
thymectomy’, which adds an additional resection of fatty tissues in the cervical and hilar regions through a T-shaped cervical/sternal incision. Their results showed an RR of 46% and
a PR of 94% in 72 cases of MG without thymoma.
Among our patients with thymomatous MG, RR was
approximately 30% and PR was approximately 80%. The RR
of a thymoma series reported by Papatestas was 10%. In
Maggi’s series, RR was 15.7% and PR was 76.0%, whereas
Evoli’s series showed a PR of 64%. The results of our series are
superior to those of the others cited here. This difference is
probably because the others included transcervical and
transsternal thymectomies, without adipose tissue resection.
These findings suggest the importance of a more extensive
elimination of thymic tissue in thymomatous MG patients as
well.
Many factors such as age at the time of operation, duration
of disease, or MG type have been reported to influence the
effects of a thymectomy. With regard to age at the time of
operation, among our patients with nonthymomatous MG,
younger subjects showed better results than older subjects,
which is consistent with other reports. Duration of disease is
an important prognostic factor. Our investigation showed
superior results among patients with disease of short duration
for both nonthymomatous and thymomatous MG. Whether
a thymectomy is indicated for patients with the ocular type of
MG has been controversial. A long-term follow-up study we
conducted, however, showed the effectiveness of an extended
thymectomy for patients with the ocular type of MG, both
with and without a thymoma.
main reasons for an incomplete resection of invasive thymomas is infiltration to the superior vena cava (SVC), recently,
resection and reconstruction of the SVC have been aggressively used. On the other hand, patients with other malignant
thymic tumors, such as thymic cancer or malignant germ cell
tumor, may not be good candidates for this procedure, as distant metastasis is frequently present at the advanced stage.
PREOPERATIVE ASSESSMENT FOR THYMOMA
Patients with an invasive thymoma often complain of
5
symptoms such as coughing, chest pain, or SVC
syndrome. The disease is first detected by a chest radiograph.
The extent of the tumor can be well evaluated by conventional chest CT and magnetic resonance imaging. Further,
venography is useful to demonstrate infiltration of the
brachiocephalic veins and SVC. An exact histological
diagnosis is very important to differentiate thymomas from
other malignant thymic tumors, especially at the advanced
stage. A CT-guided biopsy, anterior mediastinotomy, or
thoracotomy is used for this purpose.
5
PRINCIPLES AND JUSTIFICATION FOR
THYMOMA
A thymoma is a neoplasm arising from the epithelial cells of
the thymus. Most thymomas are slow-growing tumors and
are frequently associated with MG; however, the tumor cells
do not show a malignant appearance, despite their invasive
nature. Although thymomas invade surrounding structures
such as the pericardium, lungs, or great vessels, distant metastasis is quite rare. Therefore, local resectability is considered
to be an important prognostic factor. Although one of the
ANESTHESIA FOR THYMOMA
If an airway stenosis exists, endotracheal intubation while the
patient is awake should be considered. Otherwise, general
anesthesia can be induced in the usual manner. A doublelumen endotracheal tube is indicated for procedures such as a
partial lung resection. Central venous pressure should be
carefully monitored if the venous return is impaired. A thoracic epidural catheter is placed for intraoperative and postoperative pain management. In cases of MG, the anesthesia
should be managed accordingly.
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OPERATION FOR THYMOMA
Preparation for tumor resection
An extended thymectomy, including the tumor in con-
6
junction with resection of the invaded organ, is the final
goal. The anterior mediastinum is entered through a full
median sternotomy. The intact part of the thymus is first dissected as much as possible, then the invaded pericardium is
easily resected. When the mediastinal pleura is invaded by the
tumor, the pleura is incised, and the pleural cavity is
observed. If an invasion into the lung is present, partial resection is performed with a linear stapler. Thus, the thymus and
the tumor can be freed from the surrounding structures,
except for the SVC and brachiocephalic veins.
The right and left brachiocephalic veins should be dissected sufficiently distal to the tumor invading site and encircled with cotton umbilical tape. The SVC is also mobilized
and encircled with tape, either inside or outside the pericardium, depending on the extent of tumor invasion to the
SVC. The azygos vein above the pulmonary hilum and the
internal mammary vein are separated and divided between
the ligatures. The phrenic nerve is often sacrificed.
Lung
Thymus with thymoma
Aorta
SVC
RA appendage
Pericardium
resected
Left brachiocephalic
vein
Lung
Pericardium
6
Reconstruction of the left brachiocephalic vein
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and the superior vena cava
Operation for thymoma 49
Left brachiocephalic vein
In general, reconstruction is first performed
7a, b
right atrium, followed by reconstruction between the right
brachiocephalic vein and the SVC. After heparin sodium is
intravenously administered, the left brachiocephalic vein is
occluded distally with an atraumatic vascular clamp and ligated proximally, and then divided between them. An anastomosis between the distal stump of the left brachiocephalic
vein and the appendage of the right atrium is performed
using a ringed Gore-Tex 8.0-mm graft secured with a 5/0
monofilament polypropylene suture by a simple continuous
technique.
between the left brachiocephalic vein and the
7a
Ringed Gore-Tex graft
RA appendage
7b
50 Anterior mediastinal lesions
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The right brachiocephalic vein is occluded distally and
8
the SVC proximally, and both veins are divided on the
tumor side. Thus, the thymus, including the tumor, is completely removed. The SVC is reconstructed in the same manner as the left brachiocephalic vein using a ringed Gore-Tex
10.0-mm graft. When the clamps are released, bleeding may
occur from the suture lines, but these usually seal promptly.
Some surgeons believe that one brachiocephalic vein is
adequate to return blood from the upper half of the body to
the heart. Reconstruction of the right brachiocephalic vein
can be abandoned without major complications, except for
transient swelling in the right upper extremity. In this
instance, effort should be made to leave the azygos vein
intact. The stumps are closed with over-and-over continuous
sutures.
After hemostasis is accomplished, a chest tube is positioned in the anterior mediastinum. A second chest tube is
sometimes inserted in the right pleural space through the fifth
or sixth intercostal space. The sternum is then repositioned
with wire sutures, and the wound closed in layers.
Right brachiocephalic vein
Lung
SVC
Brachiocephalic artery
Left brachiocephalic vein
Aorta
Lung
Pericardium
Complications
Major complications are rarely encountered. Occlusion of the
graft, particularly that used for the left brachiocephalic vein,
sometimes occurs, because it is long and could be compressed
by the sternum and ascending aorta. When both veins are
reconstructed, however, occlusion of only one graft may not
cause a problem. Postoperative respiratory failure may be
related to the severity of the associated MG and complicated
by phrenic nerve injury. Because patients with MG have a relatively early stage thymoma, this ominous combination is
quite rare.
OUTCOME FOR THYMOMA
The clinical staging system for thymomas devised by
Masaoka, which is based on the local extension of the tumor,
has been shown to reflect the prognosis, and the significance
of staging by this system as a prognostic factor has been confirmed by several other institutions. A brief description of
Masaoka’s criteria follows:
RA appendage
Ringed Gore-Tex
grafts
8
Stage I: macroscopically completely encapsulated with
no capsular invasion
Stage II: 1. macroscopic invasion into surrounding fatty
tissue or mediastinal pleura, or
2. microscopic invasion into capsule
Stage III: macroscopic invasion into a neighboring organ,
that is, pericardium, great vessels, or lung
Stage IVa: pleural or pericardial dissemination
Stage IVb: lymphogenous or hematogenous metastasis
Among 194 consecutively treated patients with thymoma
who underwent a complete resection or subtotal resection at
our institution, the 10-year and 20-year survival rates were
99% and 90% for stage I disease, 94% and 90% for stage II
tumors, 88% and 56% for stage III disease, 30% and 15% for
stage IVa lesions, and 0% and 0% for stage IVb tumors. In
addition, the 10-year and 20-year survival rates for patients
with stage III disease were 97% and 75% when no involvement of the great vessels was present, and 70% and 29% when
these vessels were involved. Thus, involvement of the great
vessels was the single independent prognostic factor in
patients with stage III disease, by multi-variate analysis.
Further reading 51
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An invasive thymoma with involvement of the great vessels, especially involvement of the SVC, is a challenging case.
Because thymomas are usually sensitive to radiation or
chemotherapy, preoperative induction therapy may improve
the prognosis of these advanced thymomas.
FURTHER READING
Evoli A, Batocchi AP, Provenzano C, Ricci E, Tonali P. Thymectomy in the
treatment of myasthenia gravis: report of 247 patients. Journal of
Neurology 1988; 235: 272–6.
Jaretzki A III, Penn AS, Younger DS, et al. ‘Maximal’ thymectomy for
myasthenia gravis. Results. Journal of Thoracic Cardiovascular
Surgery 1988; 95: 747–57.
Kirschner PA, Osserman KE, Kark AE. Studies in myasthenia gravis.
Transcervical total thymectomy. Journal of the American Medical
Association 1969; 209: 906–10.
Maggi G, Casadio C, Cavallo A, Cianci R, Molinatti M, Ruffini E.
Thymectomy in myasthenia gravis. Results of 662 cases operated
upon in 15 years. European Journal of Cardiothoracic Surgery 1989;
3: 504–11.
Masaoka A, Monden Y. Comparison of the results of transsternal simple,
transcervical simple, and extended thymectomy. Annals of the New
York Academy of Sciences 1981; 377: 755–65.
Masaoka A, Monden Y, Nakahara K, Tanioka T. Follow-up study of
thymomas with special reference to their clinical stages. Cancer
1981; 48: 2485–92.
Masaoka A, Monden Y, Seike Y, Tanioka T, Kagotani K. Reoperation after
transcervical thymectomy for myasthenia gravis. Neurology (NY)
1982; 32: 83–5.
Masaoka A, Yamakawa Y, Niwa H, et al. Extended thymectomy for
myasthenia gravis patients: a 20-year review. Annals of Thoracic
Surgery 1996; 62: 853–9.
Mulder DG, Graves M, Herrmann C. Thymectomy for myasthenia gravis:
recent observations and comparisons with past experience. Annals of
Thoracic Surgery 1989; 48: 551–5.
Okumura M, Miyoshi S, Takeuchi Y, et al. Results of surgical treatment
of thymoma with special reference to the involved organs. Journal of
Thoracic and Cardiovascular Surgery 1999; 117: 605–13.
Papatesta AE, Genkins G, Kornfeld P, et al. Effects of thymectomy in
myasthenia gravis. Annals of Surgery 1987; 206: 79–88.
Shimizu N, Moriyama S, Aoe M, et al. The surgical treatment of invasive
thymoma: resection with vascular reconstruction. Journal of Thoracic
and Cardiovascular Surgery 1992; 103: 414–20.
Younger DS, Jaretzki A, Penn AS. Maximum thymectomy for myasthenia
gravis. Annals of the New York Academy of Sciences 1987; 505:
832–5.
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Thymectomy
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LARRY R. KAISER, MD
The John Rhea Barton Professor and Chairman, Department of Surgery, University of Pennsylvania; Surgeon-in-Chief, University of
Pennsylvania Health System, Philadelphia, PA, USA
5
HISTORY
Over the past few decades, complete removal of the thymus
gland has been shown to improve the clinical course of
patients with myasthenia gravis (MG). However, the precise
relationship between the thymus and the generation of MG
has not been completely elucidated. Blalock performed a
thymectomy via median sternotomy in 1936 for a woman
with thymoma and MG and noted an improvement in her
myasthenic symptoms. He subsequently reported on a series
of patients without thymoma who underwent thymectomy,
noting similar improvement in the clinical course of the disease. In this report of 20 thymectomies, he observed improvement in 13 of 17 survivors. To date, a prospective randomized
trial to assess the role of surgery on the clinical course of MG
has not been performed, but a number of carefully controlled
cohort studies comparing thymectomy with standard medical management have been completed. Essentially all of these
studies have shown a significantly greater incidence of remission in the operated group versus those treated with medication alone.
PRINCIPLES AND JUSTIFICATION
has been well established, though the precise mechanism for
the improvement of symptoms following thymectomy has
not been established. Following thymectomy, up to 40% of
patients with MG can be expected to have a complete
response as measured by no requirement for medication. The
time course of the improvement may vary, and continued
resolution of symptoms may occur for up to 18 months following thymectomy. Further improvement would not be
expected to occur after this time period. An additional
30–40% of patients will achieve a partial response usually
manifest by a significant reduction in the amount and type of
medication required for symptom control. A small percentage of patients fail to achieve any symptomatic relief from
their disease. Patients should understand the likelihood of
achieving a response so that an informed decision regarding
thymectomy may be made. With the development and refinement of minimally invasive approaches to thymectomy, the
risk–benefit ratio seems to be tilted toward the performance
of thymectomy even in the older patient or those with minimal symptoms. In the past when a median sternotomy was
required for thymectomy many neurologists were hesitant
about referring patients for such an extensive operation.
However, especially with the transcervical approach, such
hesitation is no longer warranted.
The presence of myasthenia gravis constitutes the most common indication for the performance of elective thymectomy.
The other main indication is the presence of a mass within the
thymus gland. Approximately 15% of patients with MG have
thymoma, while approximately 35% of patients with thymoma have MG. Patients presenting with a thymoma should
be thoroughly evaluated for symptoms of MG, and likewise
those presenting with MG should have a computed tomographic (CT) scan of the chest to evaluate the anterior mediastinum. The relationship between MG and the thymus gland
PREOPERATIVE ASSESSMENT AND
PREPARATION
Put simply, any patient with MG is a candidate for thymectomy, but this principle certainly does not imply that all
patients with the disease are referred for resection. No laboratory test or other diagnostic maneuver exists that will predict
the response to thymectomy – this only can be assessed following the procedure. Likely, this unpredictability is one of
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