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Surgical Management of Primary Mediastinal Germ Cell Tumors
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| Raja
M. Flores, MD
Division of Thoracic Surgery
Assistant Professor of Cardiothoracic Surgery
Cornell University Medical College
Memorial Sloan-Kettering Cancer Center
New York, New York |
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Patient
Selection |
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| Any anterior mediastinal mass (Figures
1, 2) must be considered suspect for germ cell tumor, especially
in a young male. Errors in diagnosis are not uncommon and can
result in mismanagement of a potentially curable patient. All
patients with an anterior mediastinal mass should have alpha-fetoprotein
(AFP), β-human chorionic gonadotropin (β-HCG), and lactate
dehydrogenase (LDH) levels drawn at the outset. The different
types of germ cell histologies are shown in Figure 3.
A number of hematologic malignancies may occur in conjunction with
mediastinal non-seminomatous germ cell tumors (NSGCT), such as acute
megakaryocytic leukemia, myelodysplastic syndrome, refractory thrombocytopenia,
refractory anemia with excess blasts, malignant histiocytosis, and
systemic mastocytosis. In approximately 80% of nonseminomatous
germ cell tumors, AFP is elevated. β-HCG is elevated in
approximately 30% to 35% of patients and may lead to gynecomastia
in a young male patient. Either tumor marker may be elevated
alone or together in any particular patient [1, 2].
The presence of any nonseminomatous element (i.e. elevated AFP), even
in a tumor that is predominantly seminomatous by histology, is classified
as a nonseminomatous germ cell tumor and treated as such. Patients
with pure seminomas should never have an elevated serum AFP; its presence
implies the presence of yolk sac tumor and embryonal cell carcinoma
in the primary or in a metastatic site. In mature teratomas,
AFP, B-HCG and LDH are normal.
Although treatment can be initiated based upon
positive tumor marker results, histological diagnosis is recommended.
There is a pathologic discrepancy of 6% between histology and fine-needle
aspiration (FNA), and difficulty may arise in differentiating germ
cell tumor from poorly differentiated carcinoma [3].
Core needle biopsy should be performed when possible and, if surgical
biopsy is warranted, an anterior mediastinotomy (Chamberlain) is usually
the procedure of choice. In diagnostic dilemmas, tissue should
be sent for genetic analysis - specifically the i(12p) chromosomal
abnormality, which is a consistent finding in germ cell tumors and
rarely observed in other tumors. Chemotherapy is the mainstay
of initial treatment and surgery should be viewed as an adjuvant to
chemotherapy. Bleomycin, etoposide, and cisplatin (BEP) is the
current standard [4, 5]. A
rapid decline of tumor marker levels with platin-based chemotherapy
treatment is associated with improved response rates and overall survival
[6]. Chemotherapy is also indicated post-surgical
resection when viable tumor is present in the resected specimen.
After initial treatment with chemotherapy, a patient with tumor marker
normalization and a persistent mass on computed tomography is the
most favorable candidate for surgical resection. Patients demonstrating
a residual mass on computed tomography and persistently elevated tumor
markers have been treated with salvage chemotherapy in the past in
an effort to obtain normal tumor marker levels prior to surgery.
This approach, however, has not improved outcome [5],
and currently our practice is to recommend surgery after initial chemotherapy
(regardless of persistently elevated tumor markers) in an attempt
to achieve complete surgical resection. If patients are to undergo
salvage chemotherapy preoperatively, this should be performed in a
clinical trial setting. In rare circumstances, post-chemotherapy
patients will demonstrate normalized tumor marker levels but no residual
mass on computed tomography. Surgery is not recommended in these
patients. Instead, they should be followed by serial computed
tomography scans. |
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| Figure 1a: Chest
radiograph of mediastinal germ cell tumor |
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| Figure 1b: Chest
radiograph of mediastinal germ cell tumor |
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| Figure 2: Computed
tomography of mediastinal germ cell tumor |
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| Figure 3: Histologic
types of germ cell tumors |
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Operative
Steps |
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| Surgical
assessment should be obtained prior to chemotherapy as well as after
treatment. Attention to the patient’s functional status,
hematologic function, and pulmonary function testing [especially the
diffusion capacity (DLCO)] is critical. Post-chemotherapy DLCO
measurement is essential because of the potential of bleomycin toxicity
leading to progressive pulmonary fibrosis. If major anatomic
lung resection is anticipated (based upon the pretreatment computed
tomography), then the amount of bleomycin administered should be limited.
The procedure is performed with a double lumen endotracheal tube in
place. Lung collapse is frequently required in order to facilitate
exposure and/or lung resection. FiO2 should be kept to a minimum
because of the potential harmful effects after neoadjuvant treatment
with bleomycin. If there is any possibility of resection of
the superior vena cava (SVC), femoral venous access should be obtained.
Incisions
Median Sternotomy
This is the most common approach for small, centrally located tumors
in the anterior mediastinum. The patient is placed in the supine
position with both arms tucked to the sides, which allows exposure
to the right or left hemithoraces, the lung hila, and mediastinal
vascular structures. However, exposure to the posterior aspects
of the lung is suboptimal and visualization of the left lower lobe
is limited.
Hemiclamshell Thoracotomy
This is our preferred approach for large tumors arising in the anterior
mediastinum and extending significantly into either the right or left
hemithorax. The exposure is a combined upper median sternotomy
and anterior thoracotomy (Figures 4, 5). The
patient is placed in the supine position, the side of the anterior
thoracotomy extension is elevated 30 degrees with a longitudinal roll
placed beneath the scapula, and arms are tucked at the sides.
Exposure is facilitated by collapse of the ipsilateral lung, allowing
for anatomical lung resection if necessary. Once the involved
lung is divided, optimal exposure to the posterolateral aspect of
the tumor is obtained; thereby allowing complete assessment of adjacent
vascular structures and phrenic nerve.
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Figure 4: Incision for
a right hemi-clamshell (Bains MS et al. The
clamshell incision: an improved approach to bilateral pulmonary
and mediastinal tumor. Ann Thorac Surg 1994;58:30-33.
Used with permission)
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Figure 5: Operative exposure
for a right hemi-clamshell (Bains MS et al.
The clamshell incision: an improved approach to bilateral
pulmonary and mediastinal tumor. Ann Thorac Surg 1994;58:30-33.
Used with permission)
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| Hemiclamshell
Thoracotomy with neck extension
If a large tumor extends into the neck area, an extension along
the anterior border of the sternocleidomastoid provides excellent
exposure, especially if dissection of the vascular structures is required.
This provides excellent exposure of the carotid and jugular vessels
(Figures 6, 7).
Hemiclamshell Thoracotomy with transverse supraclavicular extension
(trap door)
On rare occasions, resection of the subclavian vessels is necessary
with mediastinal germ cell tumors. If required, extending the
top of the sternotomy along the superior portion of the clavicle allows
adequate control of the vessels. In addition, the excision of
the medial 1/3 of the clavicle may provide added exposure (Figure
8 ).
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Figure 6: Incision for
right hemi-clamshell thoracotomy with right neck extension
(Korst RJ, Burt ME. Cervicothoracic tumors: results
of resection by the hemi-clamshell approach. J Thor
Cardiovasc Surg 1998;115:286-95. Used with permission.)
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Figure
7:Exposure for right hemi-clamshell with neck extension
(Korst RJ, Burt ME. Cervicothoracic tumors: results
of resection by the hemi-clamshell approach. J Thor
Cardiovasc Surg 1998;115:286-95. Used with permission.) |
Figure
8: Incision for left hemi-clamshell with supraclavicular
extension |
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| Clamshell
Very large tumors with extension into both hemithoraces are best
approached via this method. The patient is placed in the supine
position and the arms are either extended or flexed up over the patient’s
forehead and secured to the ether screen. A curvilinear incision
is made along the inframammary crease, extending from right to left
anterior axillary lines (Figure 9). The 4th
interspace with transverse division of the sternum usually provides
the best exposure; the mammary vessels are ligated and two Finochietto
retractors are used to provide retraction (Figures 10, 11).
The pleural reflections are incised to gain exposure to the mediastinal
structures. If one initially begins with a clamshell incision
but finds poor exposure to the superior mediastinum, an upper sternal
split may provide added exposure of involved structures.
Posterolateral Thoracotomy
A posterolateral thoracotomy may be used in a select number of
cases. However, access to the mediastinal vascular structures
is limited and, if resection of these structures is required, conversion
to a median sternotomy after dissection of the posterolateral components
of the mass may be performed.
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Figure 9: Showing clamshell
incision (Bains MS et al. The clamshell incision:
an improved approach to bilateral pulmonary and mediastinal
tumor. Ann Thorac Surg 1994;58:30-33. Used with
permission)
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Figure
10: Intraoperative exposure via clamshell (Bains
MS et al. The clamshell incision: an improved approach
to bilateral pulmonary and mediastinal tumor. Ann Thorac
Surg 1994; 58:30-33. Used with permission) |
Figure
11: Intraoperative photo of clamshell and upper sternal
split for a very large tumor |
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| Intraoperative
decision making: To resect or not to resect?
Neoadjuvant chemotherapy is very effective in treating mediastinal
germ cell tumors. However, the residual mass becomes intimate
with surrounding structures and frequently there are no discernible
tissue planes. In these cases, the surgeon is faced with the
decision whether or not to resect major structures, with the attendant
morbidity versus potentially leaving residual tumor in the chest.
Although tissue planes are distorted, one may be able to peel the
mass off from structures such as the SVC and phrenic nerve.
Some surgeons have recommended shaving a piece of tissue from multiple
areas for frozen section analysis. If only fibrosis is
evident, then peeling the mass off adjacent structures is reasonable;
if it shows tumor, then en-bloc resection is performed. However,
many lesions are mixed with necrotic and viable components and may
contain seminomatous and non-seminomatous germ cell tumor, teratoma,
carcinomatous and sarcomatous elements. Because of this, biopsy
of certain areas may not be representative of the entire specimen.
Since this method of biopsy is not always accurate, if invasion is
suspected intraoperatively, then we recommend resection of technically
resectable structures.
Our data showed residual viable tumor in 66% of cases [7].
Therefore, we have a low threshold for resecting phrenic nerve, lung,
SVC, pericardium, etc., en-bloc. Dissection is usually started
from left to right since the structures on the left are usually considered
unresectable (e.g. aorta) and the structures on the right are considered
resectable (e.g. SVC). This will allow an assessment as to whether
complete resection is possible. If so, a more radical procedure
is reasonable. Should the complete removal of all disease not
be possible, then the resection of major structures such as the SVC
or phrenic nerve may be futile and not worth the attendant morbidity.
When tumor markers have completely normalized, fibrosis will usually
be encountered at the periphery. Conversely, when tumor markers
persist, it is likely that viable tumor is present. However,
there is no steadfast rule in making the decision to resect or not
to resect a major structure.
Resectable structures
Thymus
The majority of primary mediastinal germ cell tumors arise in
the thymic tissue of the anterior mediastinum. Therefore, resection
of the entire thymus gland affords the best chance of complete surgical
resection. Because the thymus is a technically easily resectable
structure with little consequence to the patient after removal, in
the majority of cases we recommend en bloc resection of the thymus
along with the germ cell tumor mass.
Pericardium
The pericardium usually comprises the most posterior extent of
the germ cell tumor mass. Resection of this structure is not
always required for a complete resection; however, in many situations
it is resected easily with little downside to the patient. When
the involvement of the posterior margin is of concern, the pericardium
should be resected en-bloc. In certain cases, the pericardium
is reconstructed with Gore-Tex to protect the underlying structures
in the event repeat sternotomy is required.
Lung
The lung frequently requires resection in order to obtain negative
margins and to gain adequate exposure to the mediastinal structures
posterior to the mass. Since only peripheral portions of the
lung are in direct contact with the structures of the anterior mediastinum,
a wedge resection is usually sufficient in order to obtain negative
margins. Non-anatomical resection is advocated rather than lobectomy.
In rare circumstances, lobectomy and even pneumonectomy may be required
for lesions invading hilar structures. However, every effort
should be made to avoid large pulmonary resections when possible.
Very large tumors can compress the lung to the size of a fist and
may deceivingly appear to require a pneumonectomy. Once the
mediastinal portion is completely mobilized, positive pressure ventilation
is applied to the affected lung with the tumor lifted up and off the
mainstem bronchus. This maneuver helps to identify the plane
of dissection between lung and tumor.
Phrenic nerve
Every attempt to preserve the phrenic nerve should be made.
Preoperative pulmonary function tests may help with the intraoperative
decision to resect the phrenic nerve. If all tumor can be resected
cleanly and only one phrenic nerve prevents complete resection, then
the nerve should be sacrificed if the patient's pulmonary function
is adequate. When the phrenic nerve is resected, diaphragmatic
plication should be performed to prevent lower lobe atelectasis.
Innominate Veins
Transection of the right or left innominate vein alone may be
inconsequential or may result in transient arm swelling. If
this is the only structure precluding complete resection, then it
should be resected en-bloc with the specimen. However, resection
of both structures usually warrants graft interposition.
Superior Vena Cava
Tumor can generally be adequately excised from the SVC by sharp dissection.
However, if there is obvious invasion of the SVC or any suspicion
on preoperative CT scan, then large bore access inferior to the heart
(i.e. femoral vein) should be obtained.
SVC resection may be performed as demonstrated by Venuta et al., in
a previous thoracic expert technique section [8].
In situations where the SVC is completely resected, the right phrenic
nerve usually requires resection as well.
Postoperative Management
If the final pathological evaluation reveals residual viable tumor,
postoperative treatment with chemotherapy is recommended.
Post-pericardiotomy syndrome may occur after resection. Symptoms
and clinical findings include pain at the tip of the scapula, fever,
pericardial effusion, and diffuse ST elevations on EKG. Treatment
with Ibuprofen or NSAIDS generally results in improvement. |
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Preference
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- Favalaro mammary retractor
- Gore-Tex 1 mm patch for pericardial reconstruction
- Standard thoracotomy instruments
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Tips and
Pitfalls |
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If the phrenic nerve is resected, diaphragmatic plication should
be considered.
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Histologic misdiagnosis at presentation is possible.
One must be aware of a number of non-germ cell malignancies that
may occur within the tumor mass such as rhabdomyo-sarcoma, synovial
cell sarcoma, primitive neuroectodermal tumor (PNET), nephroblastoma,
and adenocarcinoma.
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Patients with choriocarcinoma as the predominant histology
may have tumors with a hemorrhagic tendency. Thus, care
must be taken in performing open surgical biopsy, mediastinoscopy,
or bronchoscopy because significant bleeding may occur.
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Major surgical exploration for biopsy, subtotal resection,
or complete resection should be discouraged because prolonged
recovery delays chemotherapy treatment.
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Resection of bilateral phrenic nerves should not be performed.
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SVC resection without should be performed with venous access
both above and
below (femoral vein) the heart.
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Results |
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| We
recently published our series from Memorial Sloan-Kettering of 32
patients who underwent post-chemotherapy surgical resection of mediastinal
germ cell tumors [7]. Histologic analysis revealed
viable tumor in 66%, teratoma in 22%, and necrosis in 12% of the specimens.
Viable tumor included embryonal carcinoma, choriocarcinoma, yolk sac
carcinoma, seminoma, and teratoma with malignant transformation to
non-germ cell histology (e.g. sarcoma). Since teratoma and residual
tumor were found in the majority of resected patients, we maintain
an aggressive approach to surgical resection of potentially involved
adjacent structures. The Kaplan Meier curve showing the survival
of the 32 patients who underwent post-chemotherapy surgery is shown
in Figure 12. |
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Figure 12: Kaplan Meier
survival curve for 32 patients who underwent post-chemotherapy
surgery (Vuky J et al. Role of postchemotherapy adjunctive
surgery in the management of patients with nonseminoma arising
from the mediastinum. J Clin Oncol 2001;19:682-88.
Used with permission.)
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References |
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1. Kay PH, Wells FC, Goldstraw P. A
multidisciplinary approach to primary nonseminomatous germ cell tumors
of the mediastinum. Ann
Thorac Surg 1987;44:578-582.
2. Nichols CR, Saxman S, Williams SD, et al.
Primary mediastinal nonseminomatous germ cell tumors. A modern
single institution experience. Cancer 1990;65:1641-46.
3. Singh HK, Silverman JF, Powers CN, Geisinger
KR, Frable WJ. Diagnostic pitfalls in fine-needle aspiration biopsy
of the mediastinum. Diag
Cytopathol 1997;17:121-126.
4. International Germ Cell Cancer Collaborative Group. International
Germ Cell Consensus Classification: a prognostic factor-based staging
system for metastatic germ cell cancers.
J Clin
Oncol 1997;15:594-603.
5. Loehrer PJ Sr., Gonin R, Nichols CR, Weathers
T, Einhorn LH. Vinblastine plus ifosfamide plus cisplatin as initial
salvage therapy in recurrent germ cell tumor. J
Clin Oncol 1998;16:2500-2504.
6. Mazumdar M, Bajorin DF, Bacik J, Higgins
G, Motzer RJ, Bosl GJ. Predicting
outcome to chemotherapy in patients with germ cell tumors: the value
of the rate of decline of human chorionic gonadotrophin and alpha-fetoprotein
during therapy. J
Clin Oncol 2001;19:2534-2541.
7. Vuky J, Bains M, Bacik J, Higgins G, Motzer
RJ, Bosl GJ. Role of postchemotherapy adjunctive
surgery in the management of patients with nonseminoma arising from
the mediastinum.
J Clin
Oncol 2001;19:682-688.
8. Venuta F, Rendina EA, Coloni GF. Surgery
of the superior vena cava: resection and reconstruction. General
Thoracic Experts' Techniques, CTSNet. Published 12/01/03 http://www.ctsnet.org/doc/8320
9. Bains MS, Ginsberg RJ, Jones WG 2nd,
et al. The clamshell incision: an improved approach to bilateral
pulmonary and mediastinal tumor. Ann
Thorac Surg 1994;58:30-33.
10. Korst RJ, Burt ME. Cervicothoracic
tumors: results of resection by the "hemi-clamshell" approach. J
Thorac Cardiovasc Surg 1998;115:286-295.
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| The pages comprising Experts'
Techniques: General Thoracic Surgical Techniques were compiled and
edited by Mark K. Ferguson,
M.D. Comments, suggestions, and contributions are welcome. |
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