Surveillance endoscopies yield large numbers of normal biopsies in low risk patients. Histology is not an ideal gold standard as patients do develop cancer without dysplasia having been detected previously. It may well be that in these patients, dysplasia was present at the time of a previous endoscopy but was not detected. Furthermore, there is incomplete agreement between pathologists on the diagnosis of dysplasia. A robust reliable tool is therefore needed which is simple to use and is available in the clinical setting.
Our preliminary data suggest that we may have such a tool. Optical biopsy only requires cheap components, is easy to use, and in its current configuration allows for accurate targeting of biopsies. The optical probe is placed in direct contact with the mucosa and measurements which suggest the absence of high grade dysplasia or cancer throughout an entire Barrett's segment have an accuracy of over 99.5%. The probe does not need to be removed from the endoscope unless a physical biopsy is taken. This makes it possible to survey a 10 cm Barrett's segment without dysplasia in two minutes, which is a time saving of at least 70%. Our modelling also suggests that ESS will decrease the number of low risk biopsies the pathologist reviews by 60% and will be associated with almost no loss in accuracy. Areas of extensive inflammation, which pathologists often find difficult to correctly classify, are less likely to be biopsied as our tool correctly detects these as non‐dysplastic. Furthermore, the results of our system could be made available to the clinician in real time which would enable immediate identification of an area where a biopsy was needed.
The accuracy of our model is based on our finding that “on average” a patient at high risk will have 2.5/17 biopsies with HGD when quadrantic samples are taken every 2 cm. This is consistent with Cameron and Carpenter's findings.24
As optical spectra are easy and quick to collect and analyse, we would envisage that clinicians might wish to take measurements every 1 cm instead of every 2 cm leading to a further increase in the accuracy of detecting dysplasia with no more than a couple of minutes added to the procedure time.25
Other optical biopsy techniques have been evaluated. Laser induced fluorescence spectroscopy was shown to accurately classify 90–96% of normal and HGD Barrett's mucosa16
and adenomatous and hyperplastic polyps in the colon.26,27
In both studies the groups were small and clear separation of test and training sets was not carried out, which will have led to overestimation of the accuracy of the technique. Raman (inelastic) spectroscopy has the advantage of interrogating tissue biochemistry and is very accurate.17
Unfortunately, it requires powerful lasers and is too expensive and slow to be used currently in clinical practice.
A true cost‐benefit analysis cannot be done using the present data as conventional biopsies were taken from all of the sites examined with ESS. This important question will need to be answered in a future prospective trial in which the equipment costs are balanced against savings in endoscopy and histopathology time when conventional biopsies are only taken when the ESS spectrum is suspicious of dysplasia or cancer.
ESS seems a good alternative because of its simplicity. It measures the physical properties of cells such as nucleus size and shape and cellular packing density, which are relevant to development of dysplasia.22
In our work, light is scattered multiple times before being detected, which makes it difficult to correlate changes in individual parameters and the optical spectra. The correlation requires complex statistics.
Others have tried to understand the correlation between the physical properties of cells and optical spectra by observing light which only undergoes a single scattering event. This is done using a polarised optical probe. Backman et al
elegantly demonstrated that alteration of single scattering events can be correlated with changes in nuclear size18
and Wallace et al
demonstrated in a small patient group the value of observing “single light scattering” events to detect dysplasia in Barrett's oesophagus.19
Combining optical biopsy approaches is likely to be better than using any single technique alone.28
We could speculate that, when incorporating Raman spectroscopy becomes feasible, the accuracy will be so enhanced that we will no longer need to take conventional biopsies at all!
ESS has been studied previously in a number of tissues as a minimally invasive diagnostic technique where access to the tissue is achieved by either direct topical access or mediated by endoscopy, including the colon and bladder.29,30,31,32,33
We have also successfully used ESS in the assessment of breast tissue and axillary nodes,34
head and neck lymph nodes,35
and bony resection margins in oral cancer.36
As scattering is induced by gradients of the optical index of refraction, ESS spectral signatures will also be altered if the refractive index of nuclei or organelles changes, for example due to changes in the amount of granularity of the chromatin.21,37
As aneuploidy is of prognostic importance in the development of oesophageal adenocarcinoma, it is interesting to speculate whether ESS could be used to detect it in vivo.38
There are limits to this technology. It is a point measurement rather than an imaging technique but it is simple and fast to use. Accuracy is less than 100% but even three expert gastrointestinal pathologists did not always agree on the degree of dysplasia, a phenomenon which is well recognised.39
As we used their consensus to train our algorithm, we cannot expect optical biopsy to be completely accurate. Our results, however, show that there is a good opportunity for the partial automation of histopathology in this difficult area. We have demonstrated elsewhere that accuracy is greater when measurements are taken ex vivo40
and patient movement during endoscopy means that there is less than perfect coregistration between optical measurements and biopsies. This will increase the error, as will the slightly different amount of tissue that is examined. ESS interrogates a volume of tissue approximately 1 mm3
whereas a conventional biopsy is larger than this. Finally, statistical analysis is open to many errors, although we were careful to use independent testing and training sets to minimise the risk of bias.
We would like to enhance the system by combining information from light that is singly or multiply scattered. Most importantly, however, we need to prospectively test our algorithm in patients.
In conclusion, elastic scattering spectroscopy offers the hope of a simple reliable tool to accurately target biopsies during surveillance endoscopy for Barrett's oesophagus.