DETECTION OF EARLY CANCER IN PERIPHERAL LUNG

The advent of multidetector row CT scanners has resulted in the
detection of multiple small nodules in many patients both in a
research setting, where CT scan is being investigated as a lung
cancer screening tool, and in the clinical setting. 57,59,60 Although
most small nodules have low risk of malignancy, persistent serial
growth on CT follow-up or change in appearance of nonsolid
lesions is worrisome for malignancy and requires investigation.
57,59,61 The diagnosis of these small peripheral lung lesions
presents particular challenges because of invisibility on fluoroscopy
and the inability of standard bronchoscopic access. Overall,
the sensitivity of bronchoscopy for peripheral lesions is 78% but
falls to 35% with lesions 20 mm in diameter. 62 Approach
with transthoracic fine-needle aspiration is also difficult even
under CT guidance because of the small size of these lesions,
and it carries a significant risk of pneumothorax.
A promising approach is to use image guidance to assist
the bronchoscopist in locating the lesions. Techniques that
have been developed include endobronchial ultrasound or
electromagnetic navigation (see Chapter 28).
Endobronchial Ultrasound for Peripheral Lesions
The use of miniaturized radial high-frequency (20 MHz) ultrasound
probes through a flexible bronchoscope enables the
localisation and characterisation of peripheral lung lesions.
Detailed 360-degree images of lesions with spatial resolution
1 mm can be seen. 63 Different patterns of ultrasound echoes
may indicate the presence of malignant or benign disease. 63–65
In general, a heterogenous internal echogenicity, absence of
linear-discrete air bronchogram, and/or a continuous hyperechoic
margin appears more suspicious of malignancy. 63–65 The
presence of two or more of these ultrasound features increases
the likelihood of malignancy to 89%, and absence of any of
these features is highly likely to exclude malignancy (negative
predictive value 85%). 65
Early use of the radial probe for localization of peripheral
lesions was followed by removal of the probe and insertion
of sampling tools into the chosen airway. The use of a guide
sheath as an extended working channel was then incorporated
into the procedure. Thus, once the lesion had been localized,
the probe was removed leaving the guide sheath in place, then
forceps and/or a bronchial brush could be advanced through
the sheath to obtain specimens. Diagnostic yields vary between
63% and 77% 66–74 (Table 19.3). Results are influenced
by size of the target lesion and position of the probe within
the lesion. 68,69,73,74 The diagnostic yield for lesions 15 mm
diameter is 40% compared with 76% for lesions 15 mm diameter.
74 If the probe is able to be positioned within the lesion,
the yield is higher at 83% compared with 61% if adjacent
to the lesion or 4% when outside the lesion. 74 In addition, the
diagnostic yield is increased with up to five cumulative sequential
transbronchial biopsies. 74
Therefore, this is an effective technique that can achieve
good diagnostic yield for peripheral lung lesions without the
associated radiation exposure of fluoroscopy or CT. However,
small lesions 10 to 15 mm remain a challenge.
Electromagnetic Navigation A promising approach
to examine small peripheral lung lesions is to use an electromagnetic
navigation guidance system to guide a small
sensor-tipped catheter to the peripheral lung, using virtual
CT as a road map. 75–81 Registration points are first marked
in the virtual CT constructed from a spiral CT scan. During
the procedure, the patient lies on top of a board that generates
a weak electromagnetic field. The physician uses the
sensor-tipped catheter to touch the same registration points
corresponding to that marked on the virtual CT (e.g., main
carina, upper-lobe entrance, middle- and lower-lobe entrance).
After that, a sheathed catheter that bends in eight
directions is maneuvered using virtual CT as a road map
similar to a global positioning system (GPS) device. Once
the target is reached, the sensor catheter is removed. Forceps
are introduced through the sheath, and transbronchial biopsies
are performed. Most of these reports used the device in
combination with fluoroscopy, which is not used for bronchoscopy
in all clinical centres. 75–79 Two centers achieved
similar results without fluoroscopy 80,81 (Table 19.4). The
diagnostic yield appears to be independent of size, but
few lesions 10 mm have been included in these studies.
Early experience showed improved diagnostic accuracy from
30% to 50% for tumors 2 cm in diameter. Accuracy
is better when the geographic miss is minimized, specifically
when the deviation from the target lesion is 4 mm. 80
Multimodality Bronchoscopic Diagnosis Diagnostic
accuracy may be improved further by the combination of endoscopic
ultrasound with electromagnetic navigation. In one series
without the use of fluoroscopy, an endobronchial ultrasound
probe was used to verify catheter placement within the target before
biopsies were performed. This technique was able to achieve
a diagnostic accuracy of 88% compared with ultrasound alone
(69%) or electromagnetic navigation alone (59%). 82
Coupling electromagnetic navigation with endosocopic
ultrasound or optical imaging such as OCT may allow better
localization and characterization of small lung lesions, increase
biopsy yield, and separate preneoplastic or early cancer lesions
from benign lesions. It may also enable delivery and placement
of fiducial markers to facilitate radiofrequency ablation, radiosurgery
or photodynamic therapy (PDT) of peripheral lesions,
and potentially allow treatment-induced changes to be monitored
in real time Advances in optical imaging such as AFB, NBI, OCT, and endobronchial
ultrasound as well as an image-guided navigation system
provide unprecedented opportunity to localize preinvasive
lung cancer and preneoplastic lesions in the lung, allow biopsy to
characterize these lesions better, and to study their natural history.
Localization of these early central lesions enables minimally invasive
endobronchial treatment without removing adjacent normal
lung tissue and, in the future, may also assist with minimally invasive
techniques for treatment of peripheral lesions.