Sonmar 5-Aminolaevulimic acid (ALA)-induced porphyrin photosensitisation is an attractive option for photodynamic therapy (PDT)

S_mary Photodynamic therapy (PDT) has the potential to destroy small tumours with safe healing of adjacent normal tissue. This study looks at the effects of PDT on the normal pancreas and adjacent tissues in hamsters using the photosensitiser meso-tetrahydroxyphenylchlorin (mTHPC). Pharmacokinetic studies used fluorescence microscopy on sections of pancreas, stomach and duodenum 1 h to 6 days after mTHPC. Highest levels of sensitiser were seen in the gastric and duodenal mucosa and in the acinar pancreas after 2-4 days. For PDT, light at 652 nm was delivered by placing a 0.2 mm diameter bare-ended fibre against the tissue. An energy of 50 J was used 2 or 4 days after 0.1 or 0.3 mg kg-l mTHPC and animals killed I to 7 days later.Maximum necrosis was seen 3 days after PDT with lesions up to 4 mm in pancreas, 4.5 mm in duodenum and 2.5 mm in stomach. By fractionating the light dose, the lesion size could be increased by 30%. The main complication was free or sealed duodenal perforation (avoided by shielding the duodenum). Partial, reversible bile duct obstruction was seen occasionally. There was no macroscopic damage to the bile ducts or major blood vessels. Apart from the duodenum, all lesions healed safely. In this animal model, only the duodenum was at risk of serious, irreversible damage. Treatment is likely to be safer in the much thicker human duodenum. mTHPC is a powerful photosensitiser and suitable for fiurther study for tumours in the region of the pancreas although care is required near the duodenum.Keywords: photodynamic therapy; pancreas; duodenum; stomach; bile duct Photodynamic therapy (PDT) involves the local activation of a preadministered photosensitiser by light of a wavelength matched to the absorption characteristics of the photosensitiser. The activated photosensitiser gives rise to the production of cytotoxic singlet oxygen (Weishaupt, 1976). In many publications it has been shown that it is relatively easy to destroy small volumes of a wide variety of tumours with PDT (Li et al., 1990. However, what matters to a patient is whether the entire tumour volume can be destroyed without unacceptable damage to adjacent normal tissues. This means that it is essential to understand what happens in the region where tumour is invading normal areas.Until now little work has been done on this aspect (Bown, 1990). Although much of the interest in PDT has centred around the possibility of selective destruction of tumours, this aspect is almost always over emphasised, and truly selective destruction of cancers is virtually impossible (Barr et al., 1990. Many normal tissues heal mainly by regeneration after PDT, but for tissues like muscle, there is only partial restoration of function (Chevretton et al., 1992). A previous report (Schroder et al., 1988) showed that PDT will produce necrosis in a chemically induced pancreatic cancer in hamsters using dihaematoporphyrin ether (DHE) but at the price of duodenal perforation. The most studied photosensitiser, haematoporphyrin derivative (HpD) and purified fraction...

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Photosensitizing properties of hypericin are well known, and the chicken chorioallantoic membrane has previously been used to test photodynamic effects of hypericin and other substances. In our study the photodynamic effect of hypericin in the ex ovo quail chorioallantoic membrane model was evaluated. Steady-state and time-resolved fluorescence spectroscopy of hypericin solution in PEG-400 and its mixture in PBS was performed to assess and characterize the process of aggregation and disaggregation of hypericin during the drug formulation preparation. A therapeutical formulation (2 µg/g of embryo weight) was topically applied on CAM into the silicone ring. Hypericin was excited by diode laser with wavelength 405 nm, fluence rate 140 mW/cm2, and fluence 16.8 J/cm2. Hypericin in 100% PEG-400 exhibits typical fluorescence spectra with a maximum of about 600 nm, while hypericin 10% PEG-400 formulation exhibits almost no fluorescence. Time resolved spectra analysis showed fluorescence decay of hypericin in 100% PEG-400 solution with a mean lifetime of 5.1 ns and in 10% PEG 4.1 ns. Damage of quail chorioallantoic membrane vasculature after photodynamic therapy ranged from hemorrhage and vanishing of capillary vessels to thrombosis, lysis, and hemorrhage of larger vessels.The presented findings suggest that quail embryos can be used as a suitable model to test the effect of hypericin and other photodynamic compounds.

Adenocarcinoma of the stomach is the 2nd most common cancer worldwide. The 5-year survival rates after curative surgical resection decline from 60–90% in stage I, to 30–50% in stage II and finally drop to only to 10–25% for patients in stage III of this disease. Surgical treatment is the only therapeutic modality that has a potentially curative effect. According to certain criteria, early gastric cancer limited to the mucosa or submucosa is indicated for endoscopic mucosal resection. In advanced gastric cancer with surgical approach, the questions of type of resection, extent of lymph node dissection and indication for splenectomy do arise. R0 resection represented with macroscopic- and microscopic-free resection margins is the ultimate goal for a surgeon. Chemotherapy is the treatment of choice in stage IV for unresectable disease. According to numerous randomized controlled trials, adjuvant chemotherapy versus chemoradiotherapy have been accepted for stages Ib–IIIb of this disease. Combination chemotherapy seems to be more effective than monotherapy. Neoadjuvant chemotherapy is administered with the aim to downstage a locally advanced tumor prior to attempting curative resection. New therapeutic possibilities include agents like angiogenesis inhibitors, human epidermal growth factor receptor family inhibitors and inhibitors of small molecules (tyrosine kinase inhibitors). Survival rates in resectable gastric cancer are influenced mainly by the depth of invasion through the gastric wall and by the presence or absence of regional lymph node involvement. Positive margins in resected patients are associated with very poor prognosis.