Abstract
Optical technologies using laser spectroscopy and imaging offer the ability to non-invasively diagnose and monitor early cancers in-vivo. For many precancers and early cancers the current standard of care relies on histopathological assessment of directed biopsies in order to obtain a final diagnosis. With optical technologies, optical biopsy based diagnosis can be achieved in real time, using automated techniques, insitu. Fluorescence imaging and spectroscopy is an emerging optical technology that offers particular promise for the diagnosis of disease, in part because of a large number of endogenous biological fluorophores. Some of the more common tissue fluorophores include the aromatic amino acids (trytophan, tyrosine and phenylalanine), the cofactor reduced nicotinamide adenine dinucleotide (NADH), flavins, porphyrins, collagen and elastin. Autofluorescence and drug induced fluorescence imaging and spectroscopy offer a means of assessing both the structural and the biochemical progression of the disease, hence, interest in its use to detect precancers has been increasing. Clinical studies at the NCC have achieved promising results in the bladder, oral cavity and cervix using exogenous porphyrin and perylene quinonoid based fluorescent markers.
It is conceivable in the near future that highly sensitive endoscopic and non-endoscopic tumour detection methods can be successfully complemented by online staging and grading, thus finally fully justifying the term ‘optical biopsy’.
In vivo confocal endomicroscopy is a non-invasive method in digital imaging of hollow organs that enables visible detection of abnormal cells on the surface and sub-surface of any hollow organ. The development of a such a method for both macroscopic and microscopic assessment was posible with a recent invention of the Optiscan fibre confocal endomicroscope by the FDA in 2002. Real time image acquisition and digistisation of optical biopsies allows for further image processing to enable derivation of menaingful real time information of the inspected site
This technique would be immensely useful in the determination of tumour margins and tumour staging during surgery. Fibre-optic fluorescence endoscopic confocal imaging technology could potentially be applied to a number of oragns systems to detect eraly disease or predisposing conditond causing premaliganat changes
Photodynamic Therapy (PDT) has been defined as the combined effect of light and a photosensitising drug to produce biological damage of therapeutic value, under conditions where either the light or the drug alone have little effect. Most PDT drugs are closely related to naturally occurring compounds and therefore have very low toxicity Whilst the concept itself is not new, developments in laser and fibreoptic technology have permitted the drug and light to be brought together within tissue in such a way as to be clinically useful. This has also been facilitated by the fact that several other ‘second generation’ compounds now in clinical trials, concentrate in certain hyperproliferative tissues relative to the surrounding healthy tissue, thus giving a favourable therapeutic ratio.
Benefits of PDT include the relative lack of trauma and pain for patients. Even where normal tissue damage does occur around the target tissue, a remarkably effective natural healing process when compared with apparently equivalent injury produced by other modalities. PDT also offers the possibility of repeat treatment, without apparent limitation. Compared to conventional chemotherapy, surgery or radiotherapy, the side-effects of PDT are minimal and largely consist of a period of skin photosensitivity, as the excess drug is excreted from the body over a period of hours to days. However, even this drawback will become unimportant as the next generation photosensitisers gain regulatory approval for widespread clinical use, since several of these exhibit much shorter optimal tissue accumulation times and excretion times. Indeed, more rapid treatment offers the possibility of PDT becoming an outpatient modality, at least for some indications.
In the past decade several thousand cancer patients have received PDT worldwide although the majority have not been part of a prospective clinical trials. It has been extremely difficult to compare results because different photosensitizers, light sources and treatment parameters have been used. Furthermore, comparison of these reports with standard cancer modalities is limited by the paucity of either long-term follow –up data or histological confirmation of complete response. The coming year will undoubtedly see a substantial expansion in the range of indications for this novel for of therapy for both oncological and non-oncological conditions.
