Needle based CLE -EBUS guided- for diagnosis and staging of lung cancer

With an incidence of 2 million cases and 1.7 million deaths, lung cancer is
amongst the commonest and deadliest cancer worldwide. To provide optimum care
it is essential that the lung cancer is staged accurately. In case of a
resectable primary tumor and no distant metastases, mediastinal nodal
involvement directs treatment. Routinely use of CT-thorax, CT-abdomen and
PET-CT has improved the detection of primary tumors and metastases but the
accuracy is still suboptimal. Tissue analysis by cytology or histology is still
required to confirm or disprove malignancy.
Conventional bronchoscopy has its limitations in lung cancer diagnosis. To
date, with the implementation of endosonographic biopsy techniques
(endobronchial ultrasound with transbronchial needle aspiration(EBUS-TBNA) and
esophageal ultrasound with fine needle aspiration (EUS-FNA) showed to be a
valuable and safe alternative.
By EUS and EBUS central tumors and all lymph node stations, except voor the
para-aortal lymph nodes, can be reached. A radial EBUS (r-EBUS) which uses a
rotating ultrasound transducer can also reach the peripheral lung tumors.
EBUS-TBNA is minimal invasive and low in costs, and although it has a good
record in detecting diseases, it has limitations in excluding diseases (missing
metastases).
With the upcoming lang cancer screening and robot guided bronchoscopy
techniques, the demand for direct feedback about the malginant status is higher
than ever.
Needle based confocal laser endomicroscopy (nCLE) is a modern imaging
technique, compatible with the conventional diagnostic aspiration needle, that
uses an excitation laser light to create *real-time* microscopic images of
tissues. Therefore this technique provides additional information regarding the
nodal status and could therefore improve the diagnostic yield of EBUS-TBNA. In
a very recent article called 'Needle-based confocal laser endomicroscopy (nCLE)
for the real-time diagnosis and staging of lungcancer' Wijmans/Annema et al.
proved that nCLE-EUS-FNA could identify malignant cell by three
characteristics. These characteristics were described as enlarged cells, darm
clumps and directional streaming.
At that time they only investigated nCLE in combination with EUS because the
nCLE probe could not fit the EBUS needle. In this moment a new EBUS needle is
available and will fit the nCLE probe. Until now no research had been done in
the field of nCLE-EBUS-TBNA. Improved characterization of mediastinal/hilar
nodes and lung lesions might lead to improved diagnosis. Ideally in the future
a target lesion is investigated and immediate bronchoscopic treatment can be
performed.

To assess the feasibility and safety of bronchoscopic/endosonography guided
needle based confocal laser endomicroscopy patients with suspected or proven
lung tumor and/or mediastinal/hilar lymph node metastases

This is a single-center observational study. Forty patients with a suspicion of
a lung tumor and/or mediastinal/hilar lymph node metastases will be included.
These patients already have an indication for bronchoscopy/endosonography and
will additionally receive nCLE measurements. By including forty patients we
expect to have at least 30 malignant samples to investigate. According to the
IDEAL-guidelines for the implementation of novel techniques, 30 is enough to
calculate a sample size for future studies. The reference standard will be
based on the cytology results of the conventional techniques and/or the
surgical pathological staging.

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Study participation includes that routine bronchoscopic/endosonography
technique will be performed under deep sedation will be prolonged by a maximum
of 10 minutes during which a CLE video will be made trough the biopsy needle.
For study purposes fluorescein will be injected intravenously through a venous
access with a 1,1% risk of adverse events (nausea is described).
Standard diagnostic procedures and subsequent treatment won't be affected by
the study participation. In our opinion we judge the burden and risk of study
participation to be neglectable.