Mucosal ablation using photodynamic therapy for the treatment of dysplasia: an experimental study in the normal rat stomach.
Surgery is the only effective treatment for dysplasia in the gastrointestinal tract with considerable associated morbidity and mortality and is difficult to justify without confirmed malignancy. Photodynamic therapy (PDT) produces localised necrosis, which can be limited to the mucosa. This study examined the mechanical properties of the normal rat stomach after PDT. The aim of this study was to measure the bursting pressure of PDT lesions in the stomach and to assess gastric emptying after producing circumferential mucosal necrosis at the pylorus by PDT. Two photosensitising agents were used--5-aminolaevulinic acid (ALA), and aluminium disulphonated phthalocyanine (A1S2Pc). Normal rats were sensitised and PDT lesions created in the stomach with red light. The bursting pressure was measured and compared with that in thermal control lesions. In further experiments, circumferential mucosal necrosis was produced at the pylorus, and animals observed for subsequent eating and weight gain. It was found that gastric bursting pressure was reduced after thermal injury, but not at any time after PDT (with A1S2Pc, but not ALA, adhesive omental reinforcement was required to maintain the gastric wall strength at one week). For the pyloric lesions, gastric emptying was permanently impaired using A1S2Pc, but with low dose ALA (20 mg/kg) had returned to normal by three days. With ALA, but not A1S2Pc, necrosis could be limited to the mucosa. In conclusion, using ALA, selective ablation of the gastric mucosa is possible, which does not reduce the strength of the stomach and only temporarily delays gastric emptying. PDT is a promising technique for the circumferential ablation of dysplastic mucosa.
Loh
C S
CS
Gastroenterology Unit, Aintree Hospital NHS Trust, Liverpool.
MacRobert
A J
AJ
Buonaccorsi
G
G
Krasner
N
N
Bown
S G
SG
D000622:Aminolevulinic Acid / Q000494:pharmacology; D000818:Animals; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D007211:Indoles / Q000494:pharmacology; D009336:Necrosis; D009942:Organometallic Compounds / Q000494:pharmacology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D012421:Rupture
D007211:Indoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; C064331:aluminum phthalocyanine disulfonate; D000622:Aminolevulinic Acid