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Endoscopic ultrasound: a useful tool to assess the mediastinum in patients with lung cancer?
  1. I Penman,
  2. R J Fergusson
  1. Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK
  1. Correspondence to:
    Dr R J Fergusson;
    ron.fergusson{at}luht.scot.nhs.uk

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EUS-FNA may help to diagnose the spread of lesions to the mediastinum in patients with lung cancer.

Mediastinal involvement either by direct invasion or by spread to lymph nodes is seen at diagnosis in up to 50% of patients with non-small cell lung cancer and has a significant impact on both treatment and prognosis. Ipsilateral or subcarinal lymph node involvement (N2 disease) is associated with a 5 year survival of 7–13%1 and usually precludes resection, but may identify a subset of patients who might benefit from neoadjuvant therapy. Contralateral nodal disease (N3) is surgically incurable with fewer than 5% of patients surviving 5 years. Accurate assessment of the mediastinum at the time of diagnosis is therefore vital for patients deemed suitable for potentially curative treatment.

To date, computed tomographic (CT) scanning remains the mainstay of imaging the mediastinum but it has limited sensitivity and specificity for detecting nodal involvement. Enlarged benign reactive nodes are frequently present in patients with a lung primary and, conversely, micrometastasis may exist in “normal” sized nodes.2,3 Thus, the finding of nodes greater than 1 cm on CT scanning usually leads to mediastinoscopy or anterior mediastinotomy to obtain histological proof of involvement. These procedures are invasive, require general anaesthesia, and have a small (1–3%) complication rate. Mediastinoscopy alone may also provide limited access to the subcarinal space and posterior mediastinum. By contrast, in 10–12% of patients with apparently negative preoperative CT scans, mediastinal nodal disease is discovered at operation.3

Endoscopic ultrasound (EUS) is a technique which has been in clinical practice for two decades and is a well established part of gastrointestinal endoscopy in many countries. By using a modified endoscope with an ultrasound transducer on its tip, unparalleled views of the gastrointestinal wall layers and the structures adjacent to the gut lumen may be obtained. Scanning from the oesophagus provides excellent views of the subcarina (level 7), aortopulmonary window (level 5), and posterior mediastinum where it is possible to resolve lymph nodes as small as 3–4 mm. Artefact associated with air in the trachea, however, greatly limits views of the paratracheal regions and anterior mediastinum. The use of curved linear array echoendoscopes allows real time visualisation of the passage of a needle, allowing safe and accurate fine needle aspiration (FNA) sampling of masses or lymph nodes adjacent to the gut lumen.

Numerous studies in recent years, reported predominantly in the gastrointestinal literature, have demonstrated the superiority of EUS over CT scanning for the detection of mediastinal node involvement.4–6 While sonographic criteria (large hypoechoic round nodes with discrete borders) may suggest malignancy, imaging alone cannot reliably differentiate benign reactive nodes from malignant ones. When FNA sampling is added, the sensitivity for detection of malignancy is 81–91% with an overall accuracy of 90–95%.4–10 In a significant proportion of patients EUS-FNA also provides the primary tissue diagnosis, especially when other methods have failed. Few studies have directly compared this technique with transbronchial needle aspiration, but available evidence suggests that the EUS-FNA method is simpler and more likely to yield a tissue diagnosis with fewer complications.11 However, EUS-FNA is not yet available to most respiratory physicians in the UK who are involved in the diagnosis and staging of patients with lung cancer.

In this issue of Thorax Larsen et al describe the role of EUS guided biopsy in two groups of patients with suspicious mediastinal masses.12 In 34 patients with known lung cancer the authors confirm the results of earlier studies with a specificity of 100% and only two false negative FNA results. In one of these patients a subsequent mediastinoscopy was also negative, with both requiring a thoracotomy to prove malignancy. Perhaps the more interesting data concern the second group of 50 patients with mediastinal masses or lymphadenopathy discovered on CT scanning but without intrapulmonary abnormality or other suspicion of lung cancer. In 36 (72%) EUS-FNA demonstrated mediastinal malignancy (N2/N3 or T4 disease) and in seven of these the cytological examination revealed small cell cancer leading to subsequent referral for chemotherapy. Of the 14 patients with a negative FNA result, three were subsequently found to have malignancy on either follow up, mediastinoscopy, or thoracotomy (one case each). Perhaps reassuringly, all five patients in both groups who were found to have inconclusive cytological findings were subsequently found to have no evidence of malignancy on prolonged follow up. There were no procedure related complications.

So far so good, but how does this information affect clinical decision making and patient management? Larsen et al attempted to assess the impact of the EUS-FNA procedure on clinical outcomes in their patients. A board of thoracic specialists reviewed the history of each patient up to the point of referral for EUS-FNA and was asked to decide on further management if EUS had not been available. This strategy was then compared with the actual clinical course after the procedure. In addition to the eight patients found to have small cell lung cancer resulting in referral for chemotherapy, a further three were found to have a specific benign diagnosis (sarcoidosis, mediastinal abscess, and oesophageal leiomyoma) and were managed accordingly. Comparing actual with planned management, if EUS had not been available, 28 of 41 mediastinoscopies (68%) and 18 of 37 thoracotomies (49%) were avoided because of the information gained from the procedure. One potential drawback with this approach is the possibility of bias, as the study authors themselves formed the panel assessing the impact of the test in question. A truly independent panel working to predefined criteria would have made the findings more robust. Although no cost effectiveness data were presented, it seems likely that an EUS-FNA strategy would have had significant cost savings, in keeping with the result of other studies.13

“EUS-FNA should have a central role in the investigation of patients with mediastinal masses”

So where do we go from here? The results of this and other studies suggest that EUS-FNA should have a central role in the investigation of patients with mediastinal masses and the staging of those with potentially resectable lung cancer, but many questions remain. Firstly, where exactly in the investigative algorithm should it occur? Patients with node positive CT scans at levels 5, 7, 8 or 9 should probably undergo EUS-FNA before mediastinoscopy for histological confirmation. However, despite the high sensitivity of EUS-FNA and its ability to resolve small nodes, it has not so far been found to be of routine value in patients with node negative CT imaging. Secondly, how does EUS compare with PET scanning? Comparative studies are still awaited but preliminary evidence suggests an advantage in favour of EUS, largely because of false positive results with PET.14 Thirdly, who should perform EUS-FNA and where should it be done? The equipment is expensive and the learning curve relatively steep. The procedure is usually performed for other indications by gastroenterologists who know little of the mediastinum and only see it when an unfortunate oesophageal perforation occurs! Training in upper gastrointestinal endoscopy is required, a skill that few if any bronchoscopists currently have. However, this has not deterred many cardiologists from learning the techniques of transoesophageal echocardiography. Perhaps it does not matter who performs the procedure as long as it is done accurately, safely, and efficiently, but for the time being it is likely to remain in the realm of the gastrointestinal endoscopist or endoscoping radiologist.

Carefully designed prospective studies are required to answer these questions and, as in the study by Larsen et al, these should include end points such as cost effectiveness, overall patient tolerability, and quality of life. The information from such work will hopefully help to guide clinicians who manage patients with mediastinal malignancy and would appear to have the potential of saving a significant number of invasive procedures.

EUS-FNA may help to diagnose the spread of lesions to the mediastinum in patients with lung cancer.

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