Transverse sternotomy extended thymectomy for generalized
myasthenia gravis over – 10 years experience in single center
Chen G1, Chen ZM1, Ma QY, Chen J, Zhu YY, Miao F, Wu N, Pang LW2
(Cardiothoracic department, Huashan Hospital, Fudan University, Shanghai. 200040)
Abstract
Thymectomy for myasthenia gravis was proven effective. Many types of approaches had been
applied by surgeons in practice. Transverse sternotomy was less reported in large series with long
term results. Further understanding about the merits and incompetence of this approach was
important for improving patients outcomes. We analyzed the data of 211 transverse sternotomy
for generalized myasthenia gravis in our center from 1998 to 2008 with 5 years follow-up results.
It was proved effective for nonthymomatous and Masaoka-Koga stage I or stage II thymomatous
patients with low complications. Overall remission rate for myasthenia gravis was 79.77% after 5
years. The compare with transcervical, median sternotomy and thoracoscopic approaches were
discussed with specifics.
Key words Myasthenia gravis Thymectomy Transverse sternotomy
Background
It’s well accepted that thymectomy can improve the overall management of generalized
myasthenia gravis since the Blalock’s case in 1930’s, although the specific biological mechanism
remains under veil. The surgical extirpation, according to literatures, provides alleviation of the
disease from 70 to 80%. There are still lots of debate on the surgery of thymus, such as the
indications, types of operation and perioperative management. Over one hundred years of
refinement (First used by Sauerbruch, 1912), miscellaneous surgery types have been developed
to resect the thymus or thymoma for myasthenia gravis. Contemporary, the extended
thymectomy is most widely adopted as standard procedure for it may provide better prognosis by
simultaneously removing ectopic thymic tissue [1, 2, 3, 4, 5, 6].
The main concerns of an operation are effect, safety, convenience, less damage, quick and
stable recovery, as well as better prognosis; all these begin with choosing a surgery approach.
The thymus in the small anterior mediastinal compartment have been accessed through all
possible approaches (Tab-1), which reflects the complexity of this disease and variation of the
surgeons’ option. Of the time, the listed approaches exist synchronically and continue to be
modified with the advance of surgery. It is important for surgeons to understanding specifics of
each approach and their results on extended thymectomy to optimize their practice. Reviewed
historically, transverse sternotomy, first introduced for thymectomy by Otto [7] in 1987, was
seldom evaluated systematically for unknown reason. Dispersed incidence of myasthenia gravis
and deficiency of long time observation for large scale of cases might explain.
Since 1990, thymectomy for myasthenia gravis was carried out in Huashan Hospital with
continuous study interest. The annual volume was over forty in our center since then. Most of
these patients were followed regularly. These thymectomies included most of the typical
approaches mentioned above. Transverse sternotomy thymectomy was frequently adopted since
1.
2.
These authors contributed equally to this work
Corresponding author. Email: Pangliewen@huashan.org.cn
1997. Early results were satisfying in our center [8]. Accumulated experience and long term
follow-up results were added to the recognition of this approach over years. We are aware that
the deficiency in clinical evidence makes it difficult to evaluate this remarkable approach.
Therefore, we present the data of ten years thymectomy for generalized myasthenia gravis
through transverse sternotomy. Compare with transcervical, median sternotomy and
thoracoscopic approaches were based on our experience and literatures.
Table-1. Approaches frequently used in thymectomy
Approach
Description
Transcervical
Neck incision over jugular notch, sternum retractor required, with or without the adjuvant
parasternal or subxyphoid incision, access the thymus cephalically
Transpleural
Thoracotomy
Anterior-lateral intercostal incision, access the thymus laterally through mediastinal pleura
Thoracoscopic
Transsternal
Median sternotomy
Longitudinal incision of the sternum, access the thymus from anterior
Partial sternotomy
“L” or reversed “T” incision of the sternum, spare the lower part of the sternum, access the
thymus from anterior
Transverse sternotomy
Transect the sternum between the 2nd and 3rd costal cartilage, access the thymus from anterior
Materials and Method
From 1998 to 2008, 416 thymectomies were carried in our center. Among these, 211 patients
with generalized myasthenia gravis (modified Osserman classification IIa, IIb, III) took transverse
sternotomy approach for thymectomy. The median age was 35 (16-75) years old. A weak majority
of male patients (116, 54.9%) over female was observed. The course of myasthenia gravis before
surgery last from months to several years. 50.7% of them were taking steroids or other
immunosuppressant.
Preoperative prepare followed the workup. The patients were evaluated for the severity of
myasthenia gravis including incidence and development of symptom, episodes of crisis, previous
treatment, as well as other co-morbidities. Physical status and laboratory results were adjusted
as the surgery require. A CT or MRI scan was assessed by radiologists and surgeons before
scheduled operation. Abnormal developments involving thoracic cage such as scoliosis, pectus
carinatum and funnel sternum were evaluated to decide whether a transverse sternotomy should
be avoided. Medicines were taken according to the instructions of consulting physicians.
Preoperative characteristics of the patients are presented in Table-2.
Table-2. Clinical characteristics of 211 thymectomized patients
Variables
Modified Osserman classification
Number (%)
IIa
61 (28.9)
IIb
104 (49.3)
III
46 (21.8)
Previous crisis
27 (12.8)
On steroids or other immunosuppressants
107 (50.7)
Ocupying lesion on CT or MRI
86 (40.8)
Comorbidities
96 (45.5)
The operation was taken under general anesthesia with intubation unless a preoperative
tracheostomy tube present. Patient lied supine with a small pillow between scapulas. A small
8cm arched skin incision was made in front of the sternum between the 2nd and 3rd sternocostal
joint. The curvature could add effective exposure with limited width. The subcutaneous tissue
was divided perpendicularly to the periosteum of sternum in the middle, and then extended
laterally to the flanks. Medial part of pectoralis major and intercostals were divided.
Intramammary arteries and veins run along the sternum about 1cm aside beneath internal
intercostal muscle. Suture ligation to the vascular stumps after dividing was necessary to prevent
accidental hemorrhage due to retraction. Post-sternal space was enlarged by blunt dissection of
finger or right-angled clamp. Cross osteotomy was performed with Gigli wire saw or electric saw
abutting the up edge of 3rd costocartilage. The anterior mediastinum was exposed by spreading
sternum stump. Implementation of extended thymectomy was the same as under the median
sternotomy. Bilateral phrenic nerves were checked extrapleurally, and cardiophrenic fat removed
completely. Mediastinal pleura and pericardium should be excised if violated. After resection, a
Redon tube for mediastinal drainage was placed through a small incision beside the incision.
Intended drainage of the pleural cavity was seldom necessary in the absence of pulmonary
parenchyma resection. The sternum stumps were approximated by two transfixing steel wires
with or without titanium plate. Then soft tissue was closed in layers. (Pic-1a-c)
Postoperative management was almost the same with median sternotomy. Patients were
allowed to walk around the second day. Drainage was pulled out the second or third day.
Postoperative steroids or immunosuppressant were given under instructions. Uneventful patients
were discharged the fourth days after operation or transferred for prolonged treatment for
myasthenia gravis. Follow-up after discharge based on outpatient circumstance.
a
b
c
Picture-1. Incision for transverse sternotomy.
a. The proper place of incision. The site of tracheostomy was
separated with the incision. It’s convenient for wound care and reduces the risk of contamination. An 8cm long skin incision is enough
for the rest of the procedure. The bottom of curved incision is aligned with the 3rd sterno-costicartilage joint. The lateral stretching
should not cross the up edge of 2nd costocartilage. b. Exposure after sternum spreading. This approach can provide adequate
exploration and manipulation even with hypertrophied adolescent thymus. c. The sternum can be re-approximated by steel wire or
titanium plate.
Results
All the 211 thymectomies were done through transverse sternotomy without elongation or
transformation of incision. 15 patients had tracheostomy. There was no massive hemorrhage due
to inadvertent manipulation. Complicated resection included pleura (36), pericardium (17),
pulmonary parenchyma (7) and angioplasty (5). 77 patients were proved to have thymoma of
Masaoka-Koga stage I (42), stage II (25) and stage III (10). One thymus carcinoma and seven
thymus cysts were identified. Postoperative drainage last from 1-10 days (mean 3.34±0.83 days)
with a total amount of 30-380ml (mean 198±72.29 ml). Postoperative pain was slight to mild
and no prolonged analgesia needed at discharge. Healing of the sternum was unremarkable
except for 4 patients. Two patients encountered unstable sternum (steel wire fixed) without
obvious discomfort. One sternum dehiscence (steel wires and titanium plate fixed) occurred after
discharge. The middle-age male patient felt down from unstable chair at home 3 day after
discharge. Emergent reoperation found proximal sternum stump avulsion. After epluchage, the
sternum was re-approximated with steel again and had a primary healing. No acute or chronic
osteomyelitis or mediastinitis happened in these patients. One patient experienced skin irritation
by wire stumps and treated by removing the wires 16 months later. The patients agreed with the
cosmetic effect of the transverse incision.
Picture-2. Primary healing of the transverse incision.
Healed wound shows cosmetic effect of transverse
sternotomy.
The continuous follow-up for myasthenia gravis was available for 173 patients. An overall 79.77%
remission rate was achieved at 5 years. Complete remission was shown in 33 (19.08%) patients
who had discontinued all medical treatment and symptomless at least for one year. Partial
remission was defined as significant improvement of symptoms with no escalation of medication,
or occasional (less than five times a year) episodes of symptoms need no maintenance treatment
or re-hospitalization. 105 (60.69%) patients achieved partial remission. 27 (15.61%) patients with
no alleviation or progression of symptoms had been taking regular treatment in outpatient
circumstance including anticholinesterase, steroids and azathioprine. Eleven patients of them
upgraded one or two kinds of medicines. Only 8 patients experienced significant progression of
myasthenia gravis 6 months after operation. Seven were re-hospitalized and 3 had tracheostomy
for prolonged respiration support. One patient died for delayed treatment of crisis.
Differential results for patients with or without thymoma were listed in Table-3. Patients with
thymoma had comparable remission rate with non-thymoma patients (81.94% vs 78.22%,
p=0.548). The CR, PR, SD, PD had no significance difference in these two group. In thymoma
group, no PD in the Masaoka-Koga stage I group, but 2 in stage II group and 3 in stage III group.
No recurrence of thymoma was found in 72 patients with thymoma.
Table-3. Result of Follow-up for myasthenia gravis at 5 years after thymectomy
Without thymoma (%)
With thymoma (%)
P value (%)
Total (%)
CR
18 (17.82)
15 (20.83)
0.619
33 (19.08)
PR
61 (60.40)
44 (61.11) *
0.924
105 (60.69)
SD
19 (18.81)
8 (11.11)
0.168
27 (15.61)
PD
3 (2.97)
5 (6.94) **
0.390
8 (4.62)
Total
101 (100)
72 (100)
173 (100)
CR=complete remission, PR=partial remission, SD=stable of disease, PD=progression of disease.
* Including one thymus carcinoma; ** One death because delayed crisis treatment
Discussion
The transverse sternotomy had been applied in dispersed thoracic diseases involving
mediastinum for cases or small series. In 1987, Otto reported the transeverse sternotomy for
thymectomy. After a period of practice, some inconvincible doubts about its capability of
complete thymus extirpation and potential compromise to achieve stable remission had shunted
lots of surgeons [4, 5, 9, 10, 11, 12]. Since that, transverse sternotomy was less reported in literatures
for myasthenia gravis especially in large series with long term follow-up data. Absence of
sufficient evidence made it difficult to evaluate this approach compared with the substantial data
of other approaches like median sternotomy or thoracoscopic thymectomy.
In most extent, extended thymectomy is the standard procedure of surgical treatment for
myasthenia gravis. We proved that transverse sternotomy was competent for not only extened
thymectomy but also Masaoka-Koga stage I and stage II thymoma from surgical stand. The
follow-up showed comparable results in neurological remission and tumor control to other
approaches. We admit the integration of adjuvant radiotherapy and immunosuppressant should
not be disappreciated. After all, there is some difference to Otto’s archetype which we think
worth mention: ⅰ) An 8cm instead of 6cm incision was adopted. ⅱ) The sternotomy should be
close to the up edge of 3rd costocartilage rather than to the 2rd costocartilage. ⅲ) Bilateral
intramammary vessels were divided. These improved the exposure and decreased blindly blunt
dissection without detriment to sternum healing.
For a thymus without tumor, this approach can provide adequate exploration and
manipulation even with hypertrophied adolescent thymus. We adopt the concept of extended
thymectomy recommended by major researchers, which covering the entire thymus gland with
upper poles spreading cephalically beyond the sterna notch and the lower lobular edge equal to
3rd or 4th costal cartilage, irregular lobular spreading underneath innominate vein and towards
pulmonary-aortic window, as well as the adipose tissue in cardiophrenic recesses, superficial to
bilateral phrenic nerves, around the converges of bilateral innominate veins [1, 4].
For stage I and stage IIa thymoma, most tumors present as an ovate or obtund lobulated lesion.
En bloc resection without exposing the tumor is apparently easy in direct view. For stage IIb
thymoma, the adhered pleura and pericardium near the tumor should also be excised without
hesitance in preventing a later proved microscopic invasion. A clear margin should be assured
with certain distance to the suspected tissue. The pleura and pericardium defect need not repair
in most situations. For radiological suspected stage III thymoma, this approach should be chosen
with discretion. In our experience, accidently encountered stage III thymomas often had a limited
range of invasion for which a radical resection still can be achieved. The involved innominate vein
can be excised with direct suture repair or reconstructed with pericardium autograft under
partial blocking or temporary complete blocking. Adventitia of ascending aorta can be peeled off
cautiously. Inadvertent cutting through the vessels necessitates immediate compression and
suture repair. A 3cm segment of involved innominate vein was excised in 2 case without
reconstruction because synchronic pericardiectomy. One developed asymptomatic
thromboembolism in left innominate vein and remained asymptomatic thereafter. The other one
was uneventful. If direct proof of stage III or beyond was found before surgery, for the good of a
best oncological result, a more aggressive approach such as median sternotomy, thoracotomy or
combined incision may be a wiser option, as long as it is indicated. The incision can be elongated
along the intercostal space if necessary, such for major pulmonary resection or phrenic nerve
exploration. We suggest radiographic analysis of stealthy invasive thymoma to avoid rushing into
awkward situation.
Median sternotomy is still the “standard approach” of thymectomy for myasthenia gravis. It is
superior in exposing anterior mediastinal and lower cervical structures. Exploring bilateral pleural
is convenient. Some authors preferred this approach for aggressive dissection to achieve
“maximal thymectomy” [9, 13, 14, 15]. But compared with extended thymectomy, patients seemed
profit little from possible additional resection of thymic foci [10, 16, 17, 18]. Substantial thymoma and
complicate procedure can be overcome. Median sternotomy is companied with more blood loss
and need strenuous hemostasis. The longitudinal split sternum is vulnerable at strutting points.
Closure of the sternum is time consuming. Tracheostomy for respiratory support imposes risk of
mediastinitis[19]. Post-sternotomy mediastinitis and osteomyelitis are difficult to handle because
inflammatory agents permeate along exposed trabeculae. Unaesthetic effect makes young and
female patients hesitant to operation [20].
A less invasive approach is always searched by surgeons. Cervical approach thymectomy has
been regarded least invasive [4, 21,22,23,24,25,26,27,288,29,30,31,32,33]. With manubrial retractor, the thymus
can be pull out of suprasternal incision with blunt dissection even with small completely
embedded thymoma. But it imposes a great danger of vascular and neural complications. A
ripped capsule is frequent found in the removed thymus with the risk of residual thymus foci. An
invasive or substantial thymoma is obviously not compatible with this approach. Inadequate
parathymic adipose tissue resection is often interrogated. Auxiliary subxyphoid incision is added
to cervical approach for dissecting low edge and cardiophrenic fat pad, but there are still lots of
restrictions.
Unilateral or bilateral thoracoscopic extended thymectomy is the most thriving and promising
solution to spare the sternum and resects ectopic thymus tissue even with early thymoma [25, 26,
27, 28, 29, 30]. Bilateral thoracoscopy seems excelled unidirectional dissection of unilateral approach
in excising parathymic tissue and exploring phrenic nerve but more time consuming for adjusting
the operation room layout and patient’s position. Adhesion of pleural cavity by pleuritis of all
causes may preclude this option. The technique difficulty is mainly because of the limited space
between intact sternum and relatively unpliable mediastinal structures especially when
presented with large thymoma. It’s still an obstacle for most thoracic surgeons to deal with stage
IIb and stage III thymomas which necessitate essential manipulation with intrapericardium
structures and great vessels. Bilateral chest drainage and intercostals neuralgia may meddle in
the recovery. There is also controversy about whether the arbitrary interruption of uninvolved
pleura may lead to the pleura implantation of thymoma. Even if the hot debating, the Long term
outcome is full of expectation for thoracoscopic approach.
As demonstrated, myasthenia gravis was alleviated for most patients after extended
thymectomy by transverse sternotomy. The long term remission rate is similar to median
sternotomy. This approach is feasible for Masaoka-Koga stage I, stage II thymomatous patients
and nonthymomatous patients. With less mechanic damage to sternum, simplified incision
closure and wound care, reduced risk of complications, compatible with tracheostomy, minimized
postoperation discomfort and optimized cosmetic effect, the transverse sternotomy approach
should be considered when other options are less preferred. For myasthenia gravis with more
advanced thymoma, other sternum separating technique or thoracotomy is desirable for more
aggressive resection. Under current perception of myasthenia gravis, choose of approach is still
the surgeon’s art of balancing as it has always been [20, 34].
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