The ability to provide the best treatment for breast cancer depends on establishing whether or not the cancer has spread to the lymph nodes under the arm. Conventional assessment requires tissue removal, preparation, and expert microscopic interpretation. In this study, elastic scattering spectroscopy (ESS) is used to interrogate excised nodes with pulsed broadband illumination and collection of the backscattered light. Multiple spectra are taken from 139 excised nodes (53 containing cancer) in 68 patients, and spectral analysis is performed using a combination of principal component analysis and linear discriminant analysis to correlate the spectra with conventional histology. The data are divided into training and test sets. In test sets containing spectra from only normal nodes and nodes with complete replacement by cancer, ESS detects the spectra from cancerous nodes with 84% sensitivity and 91% specificity (per-spectrum analysis). In test sets that included normal nodes and nodes with partial as well as complete replacement by cancer, ESS detects the nodes with cancer with an average sensitivity of 75% and specificity of 89% (per-node analysis). These results are comparable to those from conventional touch imprint cytology and frozen section histology, but do not require an expert pathologist for interpretation. With automation of the technique, results could be made available almost instantaneously. ESS is a promising technique for the rapid, accurate, and straightforward detection of metastases in excised sentinel lymph nodes.
Successful management of malignant melanoma depends on early detection and diagnostic accuracy. However studies have found a diagnostic accuracy of malignant melanoma amongst dermatologists of only 80% compared with histological diagnosis, results are generally poorer with family practitioners and dermatology trainees. Elastic scattering spectroscopy (ESS) is a non-invasive procedure that utilises elastically scattered light. A related technique, reflectance spectrometry, may discriminate between benign and malignant pigmented lesions in vivo.
Objectives: We have therefore assessed an ESS biopsy system in the diagnosis of melanocytic lesions in vivo and compared the results to both clinical and histopathological diagnosis.
Patients/Methods: One hundred melanocytic lesions from 77 patients attending our pigmented lesion clinic between 1999 and 2001 or seen at our Melanoma Day were examined clinically and divided into benign, dysplastic or malignant lesions. ESS spectra were acquired at several points from each lesion and adjacent normal skin. Lesions were then excised and sent for histological examination.
Results: Lesions were histologically classified as 12 malignant melanoma (3 in-situ), 14 dysplastic naevi and 57 benign naevi (a further 17 clinically benign naevi were included which were not selected for excision). Clinical examination had a sensitivity of 75% and specificity of 91% for detection of malignant melanoma from other melanocytic lesions and overall diagnostic accuracy of differentiating melanocytic lesions of 71%. ESS spectral diagnosis classified by linear discriminant analysis indicated a sensitivity of 84% and specificity of 65% for detection of malignant melanoma from other melanocytic lesions. However the ESS spectral diagnosis included several readings per lesion and clinically this is not relevant. Therefore an ESS per lesional diagnosis was taken as the most aggressive diagnosis. This had a sensitivity of 100% and specificity of 75% for detection of malignant melanoma from other melanocytic lesions and overall diagnostic accuracy of differentiating melanocytic lesions of 69%.
Discussion: These data suggest that ESS may be capable of differentiating malignant melanoma, dysplastic and benign naevi with a high sensitivity and provide adjuvant information to clinical examination by a dermatologist, which could be useful in the triage of melanocytic lesions.
Several research groups have been developing optical-spectroscopy methods, often mediated by fibre-optic probes, to noninvasively identify dysplasia and cancer in situ and in real time: often called 'optical biopsy'. Researchers at Los Alamos National Laboratory (Los Alamos, New Mexico) have developed the method of elastic-scattering spectroscopy (ESS). ESS is a point measurement that is sensitive to the morphological changes at the cellular and sub-cellular level, including changes in the size and/or density of the nuclei, mitochondria or other organelles. It is therefore sensitive to morphology features that a pathologist looks for during histological examination. We report on the first stages of a clinical study currently under way at the Middlesex Hospital an University College London, designed to test the ESS method for identification of dysplasia in Barrett's oesophagus. Preliminary results using elastic-scattering spectroscopy during endoscopic examination show that this technique has potential as a real-time test for in vivo detection of dysplasia or early cancer within Barrett's mucosa, or at least as a guide to assist in locating optimum sites for biopsy. Initial data sets are encouraging and the randomly chosen testing and training sets give specificities and sensitivities comparable to the accuracy of histology. It is evident that the ESS technique is proving to be convenient for the physicians given its speed and compatibility with endoscopic equipment. It is intended to begin prospective trials in the next few months to assess the systems suitability for general clinical practice.
Elastic scattering or spectroscopy offers the possibility of distinguishing between cancerous and non-cancerous tissue in suspicious breast lumps with a relatively simple optical measurement. The measurement of the relative reflection of light has previously been shown to be sensitive to both the size and distribution of intra and inter-cellular structures as well as absorption from chromophores present in the tissue. Coupling a white light source and spectrometer to optic fibres makes it possible to construct probes that can be inserted through the skin or used during the operation or on excised tissue such as the sentinel node. This `optical biopsy' is correlated with a conventional histopathological specimen obtained at the same point. Spectra have been obtained from a large number of patients with benign and malignant lesions. Some of the differences that appear in these spectra have been identified and these are discussed. To a relatively high degree of sensitivity and specificity it is shown to be possible to distinguish between malignant tumours, benign lesions and normal tissue.
Barrett's oesophagus is an increasingly common pre-cancerous condition, which occurs in patients suffering from acid reflux into their gullet. Biopsies must be taken from patients diagnosed with this condition regularly to pick up signs of pre-cancerous changes. Elastic scattering spectroscopy offers the possibility of distinguishing between benign and pre-cancerous changes in the lower oesophagus with a relatively simple optical measurement. This optical biopsy is correlated with a conventional histopathological specimen obtained at the same point. It is shown that to a relatively high degree of sensitivity and specificity it is possible to distinguish between pre-malignant patches, benign lesions and normal tissue.
Interstitial Laser Photocoagulation (ILP) is a method of destroying lesions in the center of solid organs without the need for open surgery. Under image guidance, up to four needles are inserted percutaneously into the tumor through which thin optic fibers are passed into the target lesion. Low power laser light from a semiconductor laser is delivered to gently coagulate the tissue. This dead tissue is subsequently resorbed by the body's normal healing processes. Follow up is achieved with ultrasound imaging. One study is described for assessing ILP for benign fibroadenomas. Fibroadenomas were treated to assess how laser treated breast tissue healed in the long term and we have shown that the necrosed tissue is resorbed without complications over a period of months. Nevertheless, by following treated fibroadenomas (up to 35mm diameter) with ultrasound measurement at 3, 6 and 12 months, in 14 patients, only one lesion was still detectable 12 months after ILP. In appropriate cases, ILP could be an attractive option, as it leaves no scars and should not change the shape or size of the breast. If the present studies are successful, the plan is for a multi-center trial of minimally invasive, thermal ablation of breast cancers.
Barrett's oesophagus is a metaplstic condition resulting from acid reflux that affects a small but significant percentage of the population. Detection of pre-malignant changes within this tissue may allow for preemptive treatment against oesophageal cancer. Optical biopsies using elastic scattering spectroscopy are being investigated as a possible in-situ diagnostic technique.
Elastic scattering or diffuse reflectance spectroscopy offers the possibility of distinguishing between cancerous and non- cancerous tissue in the breast with a relatively simple optical measurement. The measurement of the relative reflection of light has previously been shown to be sensitive to both the size and distribution of intra and inter-cellular structures as well as absorption from chromophores, which are present in the tissue. Coupling a white light source and spectrometer to optic fibers makes it possible to construct probes that can be inserted percutaneously or used intra- operatively to take in-vivo spectra from breast tissue or ex- vivo spectra from excised sentinel nodes. This 'optical biopsy' is correlated with a conventional histopathological specimen obtained at the same point. Spectra are reported from a large number of patients with benign and malignant lesions. Some of the differences that appear in these spectra are outlined and the uses and limitations of this technique for in-vivo diagnosis are discussed. It is shown that to a relatively high degree of sensitivity and specificity it is possible to distinguish between malignant tumors, benign lesions and normal tissue.
Elastic scattering or diffuse reflectance spectroscopy offers the possibility of distinguishing between normal and neoplastic tissue with a relatively simple optical measurement. The measurement of the reflection of light has previously been shown to be sensitive to the size and distribution of both intra and inter-cellular structures as well as absorption from chromatophores which are present in the tissue. By coupling a white light source and spectrometer to optic fibers it is possible to construct probes which can be inserted precutaneously or intra- operatively into breast tissue or which can pass down the channel of an endoscope and take in-vivo spectra of diseased and normal tissue in the Gastro-Intestinal tract. Spectra are reported from a large number of patients with a variety of benign, metaplastic, dysplastic and cancerous conditions. Some differences that have been observed in these spectra are discussed and the merits and disadvantages of 'optical biopsy' as an in-vivo diagnostic tool are examined. It is shown that to a relatively high degree of sensitivity and specificity it is possible to distinguish cancerous from normal tissue in a number of cases. The methods of distinguishing spectra and some possible modalities for their improvement are discussed.