Experimental evaluation of possible side effects of intra-operative photodynamic therapy on rabbit blood vessels and nerves.

Abstract

Tumours of the head and neck show a high local tumour recurrence rate ranging between 7 and 30% despite combined treatment modalities. To improve these data, photodynamic therapy (PDT) might be used as an additional treatment besides surgery and radio-chemotherapy. Intra-operative PDT has been proposed to "sterilise" the tumour bed after surgical tumour resection in order to kill any remaining tumour cells which are responsible for local tumour recurrences. Often, during head and neck surgery, large blood vessels and important nerve structures are exposed and could potentially be harmed by intra-operative PDT. Despite the fact that mTHPC is the most commonly used photosensitiser for head and neck tumours, there are no data on potential detrimental side effects of intra-operative PDT onto these vital structures. The purpose of this study was to use a maximal treatment protocol in rabbit observing possible damage to the blood vessels and nerve structures and thus judge the most severe event that could happen in patients. In rabbits the large blood vessels and nerve structures at the neck and at the groin area were surgically exposed and treated by mTHPC-mediated intra-operative PDT. Various treatment parameters (drug-light interval, light dosage, follow up interval) were modified in order to find the critical treatment parameters which might cause maximum tissue effects. The intention was to define the most severe clinical complications which could be expected from mTHPC mediated intra-operative PDT. The most severe tissue reactions were found at a drug dosage of 0.3 mg/kg, a drug-light interval of 24 hours and a light dosage of 20 J/cm(2). Complete necrosis was found for the muscles, fat and connective tissue within the entire treatment field. Blood vessels demonstrated severe oedema, media-hyperplasia or loosening of the endothelial layer leading to various degrees of local thrombosis but no break down of the vessel wall or any rupture was noted. Most nerves were altered by a 75% demyelisation but this did not result in any clinical symptoms. Our results have shown that mTHPC mediated intra-operative PDT used with a maximal treatment protocol (very high doses and very short drug-light intervals) has significant histological impact onto all tissue structures, but did not show any clinical symptoms in rabbits. mTHPC mediated intra-operative PDT seems to be a promising and a safe treatment option which could complement existing treatment modalities in order to improve total survival rate of tumour patients.