A comparison of outcomes after robotic open extended
thymectomy for myasthenia gravis§
Ferguel Cakara,1, Philipp Wernerb,1, Florian Augustina, Thomas Schmida,
Astrid Wolf-Magelea, Michael Sieba, Johannes Bodnera,*
aDepartment of General and Transplant Surgery, Innsbruck Medical University, Austria
bDepartment of Neurology, Innsbruck University Hospital, Innsbruck Medical University, Austria
Received 14 September 2006; received in revised form 7 December 2006; accepted 12 December 2006; Available online 16 January 2007
Objective: The aim of this study was to analyze the effect of the surgical approach on surgical and neurologic outcomes after extended
thymectomy for myasthenia gravis. Methods: A retrospective analysis of the institutional extended thymectomies for myasthenia gravis within
the last decade was performed. Patients of group A (open access by total median sternotomy; n = 10; 1996—2002) and of group B (video assisted
thoracoscopic surgery approach with the da Vinci robotic system; n = 9; 2003—2006) did not differ with regard to gender distribution, age, body
mass index, American Association of Anaesthetists score and Osserman classification of myasthenia gravis. Primary endpoints were surgical
complications and the symptomatic/neurologic outcome of the extended thymectomy. Secondary endpoints were operating times and hospital
stay. Results: Median follow-up was 74 ? 23 months in group A and 13 ? 10 months in group B. Surgical complications occurred in 4 patients in
groupA(requiring2re-interventions)andin1patientingroupB(p < 0.05).ThemediandoseofPyridostigminbromidwasreduced3and6months
postoperatively in group A to 80% and 60% of the preoperative level and in group B to 66% and 60% of the preoperative level, respectively. Within
the first postoperative year all patients of group B had an improvement of their disease whereas 2 patients of group A did not benefit from
thymectomy or had a worsening of symptoms. Operating times were significantly shorter in group A (110 (42—152) min vs 154 (94—312) min,
p < 0.05), hospital stay was significantly shorter in group B (5 (4—15) vs 10 (10—23) days, p < 0.05). Conclusions: The results of this small series
favour the robotic approach for extended thymectomy for myasthenia gravis in respect of both surgical and early neurologic outcome. However,
prospective randomized trials are required to prove a general validity.
# 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
Keywords: Myasthenia gravis; Thymectomy; Sternotomy; Robotic surgery; Thoracoscopy
Extended thymectomy is a generally accepted option in
the treatment algorithm of myasthenia gravis . It cannot
onlybenefit thymomapatientsbut isusedindependent ofthe
morphologic state of the thymus.
In myasthenia gravis a meticulous resection of the
bilaterally extended thymic gland and all retrosternal tissue
between both phrenic nerves and down to the diaphragm is
mandatory for immunologic and oncologic reasons. This is
most easily achieved with a median sternotomy but is
accompanied by the morbidity of a major thoracic proce-
dure. The minimally invasive approach by means of
conventional video assisted thoracoscopic surgery (VATS) is
feasible but technically more demanding due to limitated
vision and instrument maneuverability.
The three-dimensional vision system and the multi-
articulated instruments of the da Vinci surgical robotic
system (Surgical Intuitive, Inc., Mountain View, CA, USA)
allow an intuitive, ‘open-like’ intervention but with mini-
mally invasive access. Recently, the mediastinum has been
found to be a predestined anatomic region for robotic
procedures, and robotic extended thymectomy has been
shown to be feasible and safe [2,3].
This study aimed to determine whether the surgical and
neurologic results following extended thymectomy for
myasthenia gravis differ for the open and the minimally
invasive robotic approaches.
2. Material and methods
This study included 19 patients who underwent thymect-
omy for myasthenia gravis between 1996 and 2006. Patients
European Journal of Cardio-thoracic Surgery 31 (2007) 501—505
§Presented at the joint 20th Annual Meeting of the European Association for
Cardio-thoracic Surgery and the 14th Annual Meeting of the European Society
of Thoracic Surgeons, Stockholm, Sweden, September 10—13, 2006.
* Corresponding author. Address: Department of General and Transplant
Surgery, Innsbruck University Hospital, Anichstrasse 35, A-6020 Innsbruck,
Austria. Tel.: +43 512 504 80763; fax: +43 512 504 22577.
E-mail address: firstname.lastname@example.org (J. Bodner).
1010-7940/$ — see front matter # 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
ingroupA(openaccesswithtotalmediansternotomy;n = 10;
1996—2002) and group B (VATS approach with the da Vinci
robotic system; n = 9; 2003—2006) were analyzed in terms of
preoperative data (age, gender, American Society of
Anesthesiologists Score (ASA), body mass index (BMI)),
operation data (operating time, intraoperative complica-
tions) and postoperative data (postoperative complications,
duration of hospital stay, amount and duration of chest tube
drainage and symptomatic/neurologic outcome assessed by
means of drug reduction and DeFilippi classification of
remission (Table 1), ). The diagnosis of myasthenia gravis
was based on the patient’s history, physical examination,
positive response to anticholinesterase agents, and, when
available, positive acetylcholine receptor antibodies and
electrophysiology studies. Disease severity was classified
according to the Osserman criteria (Table 2), ).
2.1. Operative technique
Preoperative management included a CTscan of the chest
and pulmonary function tests.
An extended thymectomy with en bloc resection of the
anterior mediastinal fat tissue following the rules of Masaoka
et al.  was performed in all patients regardless of the kind
of surgical access. The adipose tissue around the upper poles
of the thymus, both brachiocephalic veins and on the
pericardium was resected meticulously. The resection
borders were the diaphragm caudally, the thyroid gland
cranially, and the phrenic nerves laterally.
The transsternal thymectomy was performed through a
complete longitudinal sternotomy. The sternal edges were
retracted with a sternal retractor. The specimen was
dissected free using blunt and sharp dissection and removed.
A chest tube was inserted into the anterior mediastinum
through a separate substernal incision, and an additional
chest tube was placed if the pleural cavity was opened. For
closure the sternal edges were approximated with six or
seven steel wire sutures.
In the robotic procedure, the port for the robotic
endoscope was positioned in the 6th intercostal space in
the middle axillary line. The two robotic instrument ports
were placed in the 3rd and the 6th intercostal space, one
An auxiliary port was positioned dorsal between the camera
forceps (Surgical Intuitive, Inc., Mountain View, CA, USA)
were attached to the robot’s left arm, which was mainly used
to grasp the tissue. Dissection was performed with a robotic
cautery hook on the right arm, starting medially to the right
phrenic nerve and working from caudal to cranial. Dissection
then continued to the substernal region, already opening the
controlateral pleural cavity. In some cases when the en bloc
extirpation of fat tissue in the lower anterior mediastinum
was hindered by collision of the left robotic arm with the
patient’s shoulder, a curved thoracoscopic grasper was
inserted via the auxiliary port to achieve better exposure.
The thymus was freed from the pericardium and dissection
proceeded as far as the thymic veins. This was followed by
dissection of the right and left upper horn and transsection of
the thymic vein(s) (Video 1). Larger vessels were clipped,
smaller ones were sealed by electrocautery. Also, the left
thymic lobe was dissected accurately from a right-sided
access. The specimen was removed in an endobag (US
Surgical, Norwalk, CT). A single chest tube was inserted into
the right pleural cavity.
Data are provided as median (range). With regard to the
small number of patients and abnormal distribution of data,
the Mann-Whitney U test was used for statistical calculation
using SPSS 11.0 for Windows. A p value of <0.05 was
patients were routinely followed-up 3, 6 and every further
6 months postoperatively. (However, not all patients
followed every particular appointment and missing data
are noted in Table 4).
Treatment groups were identical with regard to preopera-
groups did not differ with regard to gender distribution, age,
BMI, ASA scoreor Ossermanclassificationofmyasthenia gravis
(Table 3). However, follow-up was 74 ? 23 months in group A
F. Cakar et al./European Journal of Cardio-thoracic Surgery 31 (2007) 501—505
DeFilippi classification of remission
Complete remission; no medication requirements
Asymptomatic; decreased medication requirements
Improvement in symptoms; decreased medication requirements
No change in symptoms or medication requirements
Disease classification of myasthenia gravis, Osserman criteria
Mild, generalized symptoms (including bulbar)
Moderate, generalized symptoms
Acute, fulminating symptoms
Preoperative Osserman classification of patients of group A and B
versus 13 ? 10 months in group B (for the robotic approach,
which was introduced only in 2003).
No major intraoperative surgical complications were
observed in either group. Estimated blood loss was <50 cc
in all cases. There were no open conversions in group B, and
the da Vinci system itself did not show any technical failure.
All patients were extubated within 2 h after operation.
crisis, required re-intubation or mechanical ventilation.
There were three postoperative complications in group A
(30%), prompting two redo-operations: a hematoma caused a
revision in patient #1 on postoperative day 6 and a tension
pneumothorax was drained with a chest tube in patient #10.
One minor complication was a wound infection in patient #4.
In contrast, a wound infection on a port site in patient #14
was the only postoperative complication in group B (11%).
Embolization of left pulmonary artery occurred in the same
patient and was sucessfully treated by intravenous antic-
Overall operating time was 110 (42—152) min in group A
versus 154 (94—312) min in group B (p < 0.05). Drains were
removed on postoperative day 3 in group A and on postopera-
tive day 2 in group B. Postoperative hospital stay was 10 (10—
23)daysingroup A and 5 (4—15)daysingroup B(p < 0.05).Of
note is the fact that hospital stay is generally prolonged in
Austria due to less pressure from insurance companies.
Median oral pyridostigmin bromide therapy was reduced 3
and 6 months postoperatively to 80% and 60% of the
preoperative dose in group A and to 66% and 60%in group
B, respectively. Three-, six- and twelve-month postoperative
neurologic outcome according to the DeFilippi classification
ofremission is shownin Table 4.Whereas all patientsof group
B had an improvement of their disease (DeFilippi 1-3) at any
time, 2 patients of group A did not benefit from thymectomy
but experienced no change (DeFilippi 4, n = 1) or a worsening
of symptoms (DeFilippi 5, n = 1).
The percentage of patients with a thymoma diagnosed in
the resected specimen was higher in group B (4 out of 9, 44%)
in terms of Muller-Hermelink and WHO classification was
similar in both groups (Table 5). Pathology revealed totally
intact capsules in all thymoma specimens.
Myasthenia gravis is a chronic, autoimmune disorder of
the postsynaptic neuromuscular junction characterized by
fatigability of voluntary muscles. The prevalence of mysthe-
nia gravis is approximately five in 100,000 . Treatment
includes medical therapy with cholinesterase inhibitors,
immunosuppressive medication, or surgery. Thymectomy for
myasthenia gravis was first performed by Sauerbruch in 1911
. The efficacy of surgery was first proven by Buckingham,
who compared the clinical course of patients after thymect-
omy with a matched cohort receiving medical therapy .
Since then, thymectomy has become an accepted treatment
option for myasthenia gravis.
In myasthenia gravis acetylcholine receptor antibodies
block the binding of acetylcholine to its receptor at the
neuromuscular junction. The rationale for thymectomy is
that initial antiacetylcholine receptor sensitization probably
occurs in the thymus, and the thymus is a proposed site of
acetylcholine receptor antibody production. However, the
mechanism by which thymectomy improves the symptoms of
myasthenia gravis is not completely known. Removal of the
thymus may eliminate a source of continued antigenic
stimulation. Also, thymectomy may remove a reservoir of B
cells secreting antiacetylcholine receptor antibody .
The initial approach to thymectomy through a median
sternotomy [6,9,12,13] has been gradually displaced by more
minimally invasive techniques [14—16]. The recent introduc-
tion of robotic surgical systems marks the momentary end of
this process.Althoughshowntobefeasible [2,3],theefficacy
of the robotic approach for myasthenia gravis remains to be
proven. Thus, the purpose of this study was to compare our
first series of patients in which a robotic thymectomy was
performed with a former group of patients operated on with
the transsternal, open approach.
Our results suggest that robotic thymectomy in patients
with myasthenia gravis provides at least the same positive
effect as open transsternal thymectomy with regard to
improvement of neuro-muscular symptoms and drug dose
reduction, but with a lower rate of complication and re-
intervention. The clinical outcome as assessed by the
DeFilippi classification of remission favours the robotic
approach. These findings support our opinion that it is
possible to dissect and extract at least the same amount of
F. Cakar et al./European Journal of Cardio-thoracic Surgery 31 (2007) 501—505
DeFilippi classification of remission 3 and 6 months postoperative
3 months p.o.
6 months p.o.
12 months p.o.
p.o., postoperative; n.a., no data available.
Stage distribution of patients with thymoma (Muller-Hermelink and WHO)
mediastinal fat tissue in addition to thymic tissue with a
unilateral robotic technique as with the sternotomy techni-
que. Especially the pericardiophrenic fat tissue was more
easily resected with the robotic approach. Although
economic aspects were not calculated in this study, it is
evident, that the extra costs of the significantly longer
operating time in the robotic group are certainly compen-
sated by the 5 days shorter hospital stay.
Of note is the high percentage of thymomas in the
resected specimens, especially in group B patients. This
aspect of our treatment policy might deserve criticism as the
generally accepted gold standard approach in patients with
thymomas — with or without myasthenia gravis — is still the
transsternal open approach . The concerns involved with
minimally invasive techniques do exist in oncologic respects
. Indeed conventional thoracoscopy showed determina-
tion of the tumor borders and of potential infiltration into
camera image. Furthermore, precise dissection in conven-
tional thoracoscopy demands great experience and technical
skills. However, robotic surgery with the da Vinci system
enables a totally different kind of minimally invasive surgery.
The three-dimensional image on the console and the seven
degrees of freedom of the multiarticular instruments allow
very precise dissection, especially in tiny and difficult to
reach anatomic areas, as is the mediastinum. Encouraged by
laboratory and early clinical experience, we felt that we can
account for the application of the robotic technique even in
by the histologic results of the specimens and the post-
operative oncologic course of the patients, who have shown
no signs of recurrence to date. Nevertheless, we have
restricted the robotic approach to lesions smaller than 3 cm.
Today, various approaches are available for thymectomy
in addition to the open transsternal and the robotic approach
[19—25]. Comparison of two minimally invasive approaches
like the conventional thoracoscopic and the robotic thoraco-
scopic approach might have provided even more meaningful
results with regard to the effect of the robotic technology
itself. However,theaimofthisstudy wastocompare thevery
new robotic approach with the momentary gold standard
surgical approach for thymectomy, which is still the median
This study showed the robotic approach proven to provide
benefits over the momentary gold standard transsternal
approach for thymectomy in patients with myasthenia gravis.
The small number of patients and the non-randomized
retrospective design may make it very difficult to generalize
these results. The follow-up periods in both groups differed
significantly, which is a common problem when comparing
consecutive surgical techniques. Thus, this outcome analysis
can not compete with the results of prospective randomized
present the momentary standard of knowledge and experi-
ence, thereby underscoring the need for prospective trials.
 Schwendimann RN, Burton E, Minagar A. Management of myasthenia
gravis. Am J Ther 2005;12:262—8.
 Bodner J, Wykypiel H, Schmid T. Early experience with robot-assisted
surgery for mediastinal masses. Ann Thorac Surg 2004;78:259—65.
 Rea F, Marulli G, Bortolotti L. Experience with the ‘da Vinci’ robotic
system for thymectomy in patients with myasthenia gravis: report of 33
cases. Ann Thorac Surg 2006;81:455—9.
 DeFilippi VJ, Richman DP, Ferguson MK. Transcervical thymectomy for
myasthenia gravis. Ann Thorac Surg 1994;57:194—7.
 Osserman KE, Genkins G. Studies in myasthenia gravis: review of a
twenty-year experience in over 1200 patients. Mt Sinai J Med
 Masaoka A, Yamakawa Y, Niwa H. Extended thymectomy for myasthenia
gravis a 20-year review. Ann Thorac Surg 1996;62:853—9.
 Bodner J, Wykypiel H, Wetscher G, Schmid T. First experiences with the
da Vinci operating robot in thoracic surgery. Eur J Cardiothorac Surg
 Millichap JG, Dodge PR. Diagnosis and treatment of myasthenia gravis in
infancy, childhood and adolescence. Neurology 1960;10:1007—14.
 Schumacher D, Roth J. Thymectomie bei einem Fallvon Morbusbasedowii
mit Myasthenia. Mitt Gregzeb D Med Chir 1912;25:746.
 Buckingham JM, Howard FM, Benrnatz PE. The value of thymectomy in
myasthenia gravis: a computer-assisted matched study. Ann Surg
 Melms A, Schalke BC, Kirchner HK, Muller-Hermelink HK, Albert E,
Wekerle H. Thymus in myasthenia gravis: isolation of T-lymphocyte lines
specific for the nicotinic acetylcholine receptor from thymuses of
myasthenic patients. J Clin Invest 1988;81:902—8.
 Jaretzki A, Bethea M, Wolff M, Olarte MR, Lovelace RE, Penn AS, Rowland
L. A rational approach to total thymectomy in the treatment of myasthe-
nia gravis. Ann Thorac Surg 1977;24:120—30.
 Maggi G, Casadio C, Cavallo A. Thymectomy in myasthenia gravis. Results
of 662 cases operated upon in 15 years. Eur J Cardiothorac Surg
 Yim AP, Kay RL, Ho JK. Video-assisted thoracoscopic thymectomy for
myasthenia gravis. Chest 1995;108:1440—3.
 Mack MJ, Landreneau RJ, Yim AP, Hazelrigg SR, Scruggs GR. Results of
video-assisted thymectomy in patients with myasthenia gravis. J Thorac
Cardiovasc Surg 1996;112:1352—60.
 Yim AP. Paradigm shift in surgical approaches to thymectomy. ANZ J Surg
 Conkle DM, Adkins DM. Primary malignant tumors of the mediastinum.
Ann Thorac Surg 1972;14:533—67.
 Kern JA, Daniel TM, Tribble CG. Thoracoscopic diagnosis and treatment of
mediastinal masses. Ann Thorac Surg 1993;56:92—6.
 Cooper JD, Al-Jilaihawa AN, Pearson FG. An improved technique to
facilitate transcervical thymectomy for myasthenia gravis. Ann Thorac
 Mack MJ, Scruggs G. Video-assisted thoracic surgery thymectomy for
myasthenia gravis. Chest Surg Clin N Am 1998;8:809—25.
 Mineo TC, Pompeo E, Lerut T. Thoracoscopic thymectomy in autoimmune
 Milanez de Campos JR, Filomeno LTB, Marchiori. Parital sternotomy
approach to the thymus. In: Yim APC, Hazelrigg SR, Izzat MB, editors.
Minimal access cardiothoracic surgery. St Louis, MO: WB Saunders; 2000.
 Granone P,MargaritoraS,CesarioA.Thymectomyinmyastheniagravisvia
video-assisted infra-mammary cosmetic incision. Eur J Cardiothorac Surg
 Novellino L, Longoni M, Spinelli L, Andretta M, Cozzi M, Faillace G,
Vitellaro M, De Benedetti D, Pezzuoli G. ‘Extended’ thymectomy without
sternotomy, performed by cervicotomy and thoracoscopic techniques in
the treatment of myasthenia gravis. Int Surg 1994;79:378—81.
 Zielinski M, Kuzdzal J, Szlubowski A. Transcervical-subxiphoid-videothor-
acoscopic ‘maximal’ thymectomy — operative technique and early
results. Ann Thorac Surg 2004;78:404—9.
Appendix A. Conference discussion
Dr M. Dusmet (London, United Kingdom): I would like to challenge you just
a littlebitonacoupleofpoints. First ofall, ifyouread slightlyolder literature,
you’ll find three series, Papatestas, Maggi, and the Levasseur group in Paris,
1,700 patients — I think that’s a big enough number — of transcervical
thymectomy, and I think that you’ll find that extended thymectomy, the gold
F. Cakar et al./European Journal of Cardio-thoracic Surgery 31 (2007) 501—505
standard, is a somewhat difficult concept to really sustain. If you want big
numbers, 1,700patients, that’spretty bignumbers.Transcervical thymectomy
gives excellent results. So I challenge you that the extended transsternal
thymectomy is perhaps not the only gold standard, especially if you want
minimally invasive techniques.
The second thing that I’m slightly surprised by is the 10-day average stay
for a transsternal thymectomy. I find that when I split the sternum and do a
simple thymectomy, most of my patients are going home on day 3, day 4. So
why are your patients spending 10 days in the hospital just because they have
had their sternum split?
Dr Bodner: I think you are definitely right. As mentioned, there is a variety
of different approaches, and maybe it’s not only the transsternal approach to
becalled thegoldstandard;however,it’sanapproachwhichgives anexcellent
exposure to all of the mediastinum, and therefore I think for a variety of
surgeons for a very long period of time it has been accepted as the gold
standard, and different minimally invasive or semi-minimally invasive or
combined approaches have been established.
To your other question, I think that’s also a question of policy within
different nations and states. We feel less pressure by the insurance companies
regarding the period of hospital stay. And we do not send them back to any
referring hospital, but we discharge them and they go home. So with our stay,
they usually go home in the times as shown on these slides.
Dr Dusmet: When I said discharged home, I meant discharged home, not
discharged to another hospital. I meant home, taking care of themselves, on
day 3 and day 4.
Dr Bodner: I definitely accept your point of view. I just wanted to say that
in our country these times are quite usual.
Dr P. Van Schil (Antwerp, Belgium): I agree completely that the robot
allows for a very precise anatomical dissection of the thymus. At the breakfast
session yesterday, there was an ongoing discussion whether you should do it
from the left or the right side or combine it with a cervical or subxiphoid
incision. Which technique is your preference?
Secondly, regarding the indications for robotic thymectomy, you said that
you also included patients with thymoma. So in your series, did all the patients
have thymic hyperplasia and some also had thymoma, or were there cases with
thymoma without myasthenia? Could you comment on that also?
Dr Bodner: Regarding your first question, Professor Rueckert has a very
large experience on thymectomies. He prefers the left-side approach. We
always do it from the right side. We did two cases from the left side after
talking with him, but we still feel that we have advantages from the right side.
We have done now about 25, 27 thymectomies with the robot. In this study
all patients were myasthenia patients and some of them also had thymoma. Of
course, there were other patients with thymoma but not with myasthenia
gravis not included in this study. There were other patients without thymoma
also in this study.
Dr M. Zielinski (Zakopane, Poland): I would like to support your point of
view regarding the gold standard of thymectomy and to defend you against Mr
the gold standard. Additionally, I would like to add that I also agree with you
that there is no need for early discharge of patients after sternotomy. I think
that 3 or 4 days is too early, in my opinion. So I totally agree with you. On the
other hand, I cannot agree that robotic thymectomy gives you the opportunity
to remove as much as during complete sternotomy.
Dr Bodner: The fact that there is such a variety of different approaches for
me shows that there is not a perfect approach, and therefore I think these
different opinions are justified and we will go on discussing it.
Dr J. Rueckert (Berlin, Germany): I have two comments. The first thing, I
would strongly recommend using the MGFA guidelines for functional analysis of
of the events, of any event of improvement. The second thing is that the
debate between transcervical and transsternal exposure and approaches has
never ended. I think there are new data from Kaiser from Philadelphia. We
know that the transcervical incision gets good results, but it was never aimed
at achieving a radical and complete thymectomy. Proponents have the opinion
that it’s not necessary to have a complete thymectomy, and the robotic
approach combines the striving at radicality and the most minimal invasion,
and that’s the advantage.
Dr Bodner: Thank you very much. Of course, we will do this. We know your
publications and your presentations 3 days ago, and, of course, we will also do
this analysis with our patients.
Appendix B. Supplementary data
Supplementary data associated with this article can befound, in the online
version, at doi:10.1016/j.ejcts.2006.12.016.
F. Cakar et al./European Journal of Cardio-thoracic Surgery 31 (2007) 501—505