European Gastroenterology & Hepatology Review, 2006;1:17-19
Although considered a novel form of therapy, photodynamic therapy (PDT) is based on natural and universal photobiological reactions. Basic photodestructive and photosynthetic reactions started to evolve over 2,700 million years ago within bacteria. The exploitation of the fundamental process of photodestruction can eradicate diseased tissue with great precision.
The aim of PDT in the oesophagus is the targeted local destruction of abnormal cancerous or precancerous tissue. It is a minimally invasive therapy, with the advantage that the normal architecture and some normal tissue can be preserved. The technique relies on the generation or the administration of a photosensitiser, which localises within the dysplastic or cancerous tissue. At certain times after administration, there exists a concentration differential of 2:1 to 3:1 between the cancer and normal structures. Selective tumour destruction can be achieved if the photosensitiser is administered under certain dosage conditions. This is at present not fully exploited in clinical situations.1 In addition, very precise targeting of the light delivery at endoscopy to the area of disease produces a highly localised effect. There is clear attraction of this dual selectivity to minimise non-essential damage. PDT requires a photosensitiser, light, oxygen and a substrate to interact with and destroy. Generally, a synthetic photosensitiser is administered intravenously, with a period of time (48 to 72 hours) allowed for its preferential retention or accumulation in the tissue prior to activation with appropriate wavelength light, usually from a laser. Photosensitisers accumulate in rapidly growing tissue, blood vessels and the supporting tissue that grows with malignant tumours. A period of general photosensitivity will occur with most agents. All photosensitisers have a specific action spectrum (thewavelengths of light that are absorbed to produce an effect). On the delivery of light, the photosensitiser is excited to a higher state. It then transfers this light energy to another molecule, usually oxygen, to produce toxic, highly reactive species that destroy tissue. A critical threshold level of toxic photoproduct is required because the cells have developed mechanisms to withstand this oxidative damage. Once these defences are overwhelmed, the cell is fatally wounded and necrosis or apoptosis is inevitable.
It is possible to generate a photosensitiser within the cells by exploiting the natural porphyrin biosynthesis pathway. If 5-aminolaevulinic acid (5-ALA, a precursor of haemoglobin) is administered in excess, the result is an intracellular accumulation of the endogenous photosensitiser protoporphyrin IX (PpIX). The level of systemic photosensitisation is minimised to a few hours and the 5-ALA can be administered orally, dissolved in fruit juice.
A major disadvantage appears to be that the depth of necrosis is very limited and eradication of tumours deeper than 2mm may be difficult. Early studies in the oesophagus indicated that necrosis does occur, but eradication of macroscopic tumours was difficult.2–4 This critical limitation may be usefully exploited if therapy is designed to eradicate highgrade dysplasia in Barrett’s oesophagus. The depth of damage is much greater for the systemically administered photosensitisers.
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