The Role of Videomediastinoscopy in Staging NonSmall Cell Lung Cancer
Ivan Bačić1, Rade Škarica1, Nina Sulen2, Zvonko Zadro3, Nataša Lisica-Šikić4, Robert Karlo1,
1Department of Surgery, General Hospital Zadar, Zadar, Hrvatska
2Department of Anesthesiology and Intensive care, General Hospital Zadar, Zadar, Hrvatska
3Department of Surgery, General Hospital Karlovac, Karlovac, Hrvatska
4Department of Pathology, General Hospital Zadar, Zadar, Hrvatska
Lung cancer is the most frequent malignant disease and the leading cause of death
from malignant diseases in the world and its incidence is increasing . At the time when
diagnosis is established most patients have advanced disease and are not candidates for radical
surgical treatment. Patients without distant metastases are subjected to various diagnostic
methods to detect metastases in mediastinal lymph nodes that make up the path of lymph
drainage from the lungs. The most reliable invasive diagnostic procedures for detecting
metastases in mediastinal lymph nodes are videomediastinoscopy and endobronchial
ultrasound with transtracheal puncture.
In the absence of mediastinal lymph node, metastases surgrey is the treatment of
choice. If mediastinal lymph nodes are positive for metastases ,multimodal treatment is
At the Department of Thoracic Surgery, General Hospital Zadar,
videomediastinoscopy for the staging of primary non small cell lung cancer has been
performed routinely since September 2009.
Key words: lung cancer, staging of lung cancer, surgical treatment of lung cancer;
Lung cancer is the leading cause of death from malignant disease worldwide and its
incidence is increasing. In 2008. in the United States 215 000 people were diagnosed with
lung cancer and 161 840 died. More people die annually from lung cancer than from breast,
colon and prostate cancer together1,2.
Five year survival rate in patients suffering from lung cancer is increasing slowly; in
1976 it was 11.9%, and in 2000 it was 15%. The main reason for the poor survival rate lies in
the fact that 40% of patients have metastatic disease at the moment the diagnosis is
In patients diagnosed with lung cancer, it is necessary to carry out a diagnostic
evaluation to determine the stage of the disease. Staging provides adequate information about
the spread of the disease and it is crucial for determining the strategy of treatment and
prognosis4. Staging is used for non small cell lung cancer. For small cell lung cancer, which
occurs in 10 - 15% of cases, invasive staging is not performed because this tumor has
different biological features and is rarely subject of surgical treatment.
In the absence of distant metastases, the involvement of mediastinal lymph nodes is
the most important prognostic factor in patients with non small cell lung cancer and
mediastinal lymph node status determines the treatment strategy.
Primary surgical treatment of lung cancer with metastasis to ipsilateral mediastinal
lymph nodes (stageIII A) gives poor results. Patients who have been subjected to the primary
surgical treatment in stage III A have a five year survival rate of 7 - 14%5. Adjuvant
chemotherapy can not often be completed because of the poor general condition of the
patients who are recovering from surgery6.
Chemotherapy, radiation or a combination of both methods are used as neoadjuvant
treatment7. Neoadjuvant therapy offers several potential advantages. Theoretically, it acts on
the tumor cells before they produce resistant clones7. Patients can also receive a full dose of
drugs because they are not in the postoperative recovery phase. Therapy carried out in such
conditions often results in tumor reduction and eradication of the disease from mediastinal
If neoadjuvant therapy eradicated the disease in lymph nodes (downstaging) or if the
disease is stable meaning there was no progression, patients are rendered candidates for
surgical treatment9. After the implementation of neoadjuvant therapy and surgery, the five-
year survival rate for patients with stage III A disease is about 25%6-9.
Staging of disease
The international system for the staging of lung cancer is based on the assessement of
the extent of the primary tumor (T), the spread to the regional lymph nodes (N) and the
presence of distant metastasis (M).The combination of T, N and M is then used to give the
stage of the disease (I-IV). The last revision of the TNM classification of lung cancer was in
The status of mediastinal lymph nodes is the most important factor which determines
the treatment strategy. It is also used to evaluate the efficiency of neoadjuvant therapy7.
For clinical work it is necessary to map lymph nodes in the mediastinum in nodal
Such a map was developed by Mountain and Dresler11 and accepted by all relevant
world organizations which deal with the treatment of lung cancer7,10,12.
According to this map mediastinal lymph nodes are located in nine nodal positions
while five other nodal positions are located in the lungs. Each nodal position is precisely
There are several types of staging. The two principal ones are:
- clinical (non-invasive): cTNM
- pathology (invasive): pTNM
Clinical staging is based on history, physical examination, laboratory findings and
All patients who are treated for suspected lung cancer should have a chest X-ray. It
serves as the basis for comparison with further scans.
Standard chest X-rays can reveal signs of advanced disease (eg pleural effusion,
secondary lesions in the lung parenchyma, destruction of the ribs and elevated diaphragm
which indicates involment of phrenic nerve)13.
Computed tomography – CT
CT scan allows much better visualization of the intrathoracic status. Besides
determining the tumor size, mediastinal and vascular invasion and the involment of airways it
can also suggest the lymph node involvement. The disadvantages of CT staging are the
inability to distinguish benign from malignant mediastinal lymphadenopathy and the inability
to detect microscopic metastases. By CT criteria, suspicion of lymph node metastases is
made if its short-axis diameter is greater than 10 mm. The sensitivity of this method is 57 -
70% and the specificity is 59-82%13.
Integrated positron emission tomography - computed tomography (PET-CT)
This method can detect occult disease. Lung cancer cells have an increased
metabolism and therefore receive increased Fluoro-Deoxy-Glucose (FDG). By PET criteria
lymph node is considered metastatic if its metabolic activity is increased 1.5 times compared
to the baseline. This method has a sensitivity of 90%. Despite this high sensitivity histological
confirmation of metastases is requred due to its low specificity. Inflammation and infection
can give false positive results which can result in upstaging14.
There are controversies about the definition of pathological staging. Some believe that
the pathological stage of the disease can be established only after surgical exploration of the
hemithorax and mediastinum.
Others accept that the pathological stage can be determined based on the tissue
samples obtained by invasive diagnostic methods7.
Invasive surgical staging
Because of the high sensitivity (90%), low percentage of false negative results (10%)
and rare complications, videomediastinoscopy is recommended by the European Society of
thoracic Surgeons (ESTS), as the "gold standard" for the invasive staging of lung cancer10.
It is performed under general anesthesia. The patient lies on his back with the
extension of the neck. The incision is carried transversely 1 cm above the jugulum. After the
incision of the pretracheal fascia an optical-working instrument - videomediastinoscope
(Richard Wolf, Germany) is introduced. With a bimanual technique of preparation the upper
mediastinum lymph nodes are exposed.
By cervical videomediastinoscopy the following nodal positions can be sampled: high
mediastinal lymph nodes (group 1), left and right upper paratracheal (group 2L and 2R), left
and right lower paratracheal (group 4L and 4R) and subcarinaln lymph nodes (group 7 ).
There are no internationally accepted recommendations on the number of nodal
stations that should be retrieved during cervical mediastinoscopy.
American Association of Thoracic Surgeons (ATS) recommends to sample all
available nodal positions. It includes the lymph nodes in nodal positions 2L, 2R, 4L, 4R, 7, 10
L and 10 R (left and right tracheobronhal). The recommendation is to perform left parasternal
mediastinothomy for the lymph node sampling in nodal positions 5 and 6 (subaortal and
anterior mediastinal) in patients with the cancer of left lung.
Working Group of the European Association of Thoracic Surgeons (ESTS) states that
there are two standards for mediastinoscopy:
- ideally, sampling of the lymph nodes in nodal positions 2L, 2R, 4L, 4R and 7
should be performed.
- for routine clinical practice lower standard can be accepted which includes
sampling of the lymph nodes in nodal positions 4L, 4R, and 7.
In patients with left lung cancer it is necessary to sample lymph nodes in positions 5
and 6 (subaortal and anterior mediastinal)10.
In these cases, cervical approach is complemented with Chamberlain’s anterior
mediastinothomy or with VATS or extended mediastinoscopy is performed within the plane
of the dissection in the area in front of the aortic arch and its branches13.
The advantage of mediastinoscopy when compared to the fine-needle aspiration biopsy
(FNA) is that it can gain a more complete insight into the status of lymph nodes in
mediastinum including the contralateral side. This may be significant in patients with
metastases in the lymph nodes of one nodal station. It allows differentiation of extra and
intracapsular metastasis and it also allows differentiation of nodal metastasis and direct tumor
Complications of videomediastinoscopy are bleeding from large mediastinal blood
vessels, pneumothorax, recurrent laryngeal nerve injury, injury of the esophagus and trachea
and bronchial injury. Complications occur very rarely (2%). Most severe complications
resulting in death occur in 0.008% of cases7,14.
The sensitivity of cervical mediastinoscopy ranges from 72 to 89%. The reason for the
suboptimal sensitivity of cervical videomediastinoscopy lies in the fact that some nodal
positions (5, 6, the posterior parts of group 7, 8, and 9) are not reachable with
In 2007. Kuzdzal and al. compared standard mediastinoscopy to extended
transcervical mediastinal lymphadenectomy (VAMLA) and demonstrated increased
sensitivity in detecting metastases to mediastinal lymph nodes using VAMLA. It is a
technique of the extended dissection of mediastinal lymph nodes and requires special
instruments. VAMLA has a sensitivity of 94% and specificity of 100%21.
These preliminary data suggest that VAMLA combined with R0 resection could have
a positive therapeutic effect. Besides somewhat more intensive postoperative pain, incidence
of complications is not higher when compared to standard cervical videomediastinoscopy.
In patients with left lung cancer more aggressive TEMLA (transcervical extended
mediastinal lymphadenectomy) can be performed. This technique requires elevation sternum,
dissection is done in front of the aortic arch, and the lymph nodes of nodal groups 1, 2L, 2R,
3, 4L, 4R, 5, 6, 7 and 8 are reachable 2.
Anterior mediastinotomy by Chamberlain
Predilective lymph nodes for metastatic cancer of the left upper lobe are those in nodal
position 5 (subaortal). With the incision in the second or third intercostal space these lymph
nodes can be accessed. This method is usually done in addition to mediastinoscopy for cancer
of the left upper lobe.
VATS (Video assisted thoracoscopic surgery)
Video-assisted thoracoscopic surgery can be used for the sampling of mediastinal
lymph nodes. It is limited to evaluating only one side of the mediastinum. Because of low
sensitivity (50%) it is rarely used for the evaluation of mediastinal lymph nodes18,19.
It is an endoscopic method for visualization of bronchial tree and sampling using
endobronchal biopsy, sampling brush and bronchial lavage.
Blind transbronchial fine needle aspiration cytology (TBNA)
It is also known as Wang's method. It is commonly used for sampling subcarinal
lymph nodes (group 7). The sensitivity of this method is about 70% with 30% false negative
Endobronchial ultrasound with transbronchial biopsy (EBUS-TBNA)
To perform this method a flexible bronchoscope equipped with a convex ultrasound
probe is used in order to enable visualisation of lymph nodes before the needle biopsy.
Nowdays, along with invasive mediastinoscopy, it is the most relevant method for mediastinal
lymph node staging. The issue whether this method is as reliable as videomediastinoscopy for
invasive staging has not been solved yet. There is also controversy about the claims that it is
less invasive because in over 60% of cases EBUS-TBNA is performed under general
anesthesia. Otherwise it is difficult to collect adequate samples because patients are restless,
the procedure is very uncomfortable and the materials taken with a small diameter needle
may result in an inadequate intake of the sample and produce false negative results16. In the
meta-analysis published by Adams et al. the sensitivity of this method is 70 - 88%17. In the
evaluation of 17 studies on EBUS-TBNA method conducted by the American College of
Chest Physician (ACCP), it showed 24% false negative results14.
Due to its suboptimal negative predictive value, the ACCP recommendation is that in
the case of non malignant EBUS-TBNA findings mediastinoscopy should be performed to
Esophageal endoscopic ultrasound with needle biopsy (EUS - FNA)
This technique is limited by poor access to the upper mediastinal lymph nodes, which
are the most common sites for metastases in lymph nodes. It is still useful in the evaluation of
lower mediastinal lymph nodes (nodal positions 8 and 9) and can therefore be combined with
EBUS and mediastinoscopy14.. Needle biopsy of mediastinal lymph nodes through the wall of
the esophagus can be done with a negligible risk of infection.
For an optimal therapeutic approach to patients suffering from lung cancer it is
necessary to determine the stage of disease. In the absence of distant metastases, mediastinal
lymph node status is crucial in the therapeutic strategy. The status of lymph nodes that was
determined by non-invasive staging requires histological confirmation.
For invasive staging ,videomediastinoscopy and EBUS-TBNA have by far the highest
sensitivity and the lowest percentage of false negative results. Recommendations of medical
associations that deal with treatment of lung cancer (ACCP, ESTS, AATS) are the use of
videomediastinoscopy or EBUS-TBNA for the staging of patients with discretely increased
mediastinal lymph nodes.In case of negative EBUS-TBNA findings, mediastinoscopy should
be performed to confirm these findings.
In patients who do not have enlarged lymph nodes, videomediastinoscopy is a
preferred method because of its greater sensitivity and lower percentage of false negative
results, although EBUS-TBNA comes to mind if the confirmation of the negative result with
videomediastinoscopy are planned.
In patients with clinical N2 disease videomediastinoscopy is a preferred method to
exclude N3 disease. Given the high percentage of false negative results of EBUS-TBNA if
lymph nodes are not enlarged N3,the disease can be overlooked in 24% cases using this
And last but not least, there is the issue of the cost of both methods. The equipment
for videomediastinoscopy is significantly less expensive than the one for EBUS, which, in
terms of county hospitals, is an extremely important item.
From the above-mentioned, it is evident that videomediastinoscopy is a method of
choice for the invasive staging of the primary non small cell lung cancer.
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Lymph node sampling in lung cancer: how should it be done?
Tsuguo Naruke*, Ryosuke Tsuchiya, Haruhiko Kondo, Haruhiko Nakayama, Hisao Asamura
Division of Thoracic Surgery, National Cancer Center Hospital, 1-1, Tsukiji 5-chome, Chuo-
ku, Tokyo 104,
*Corresponding author. Tel.: +81-3-5447-2468 +81-3-5447-2468 ; fax: +81-3-5447-2468