THE CONTRASTING MECHANISMS OF COLONIC COLLAGEN DAMAGE BETWEEN PHOTODYNAMIC THERAPY and THERMAL INJURY

Barr, Hugh; Tralau, C. J.; Boulos, PB; MacRobert, AJ; Tilly, Rita; Bown, Stephen G.

doi:10.1111/j.1751-1097.1987.tb04850.x

Cited by 124 publications

(60 citation statements)

References 9 publications

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“…The most likely explanation is that both the submucosa and the muscle layer of the hamster duodenum are extremely thin (0.06-0.3 mm) which would make them more vulnerable than the stomach. Earlier work has shown that the main mechanical strength of the colon after PDT damage comes from collagen in the submucosa (Barr et al, 1987), and the same is likely to be true in the duodenum. One Thus PDT with mTHiPC in the normal hamster can produce necrosis in normal pancreas, biliary tree, stomach and duodenum, but the only organ in which this necrosis produces serious complications that do not resolve spontaneously is the duodenum.…”

Section: Dis Assimentioning

confidence: 95%

Distribution and photodynamic effects of meso-tetrahydroxyphenylchlorin (mTHPC) in the pancreas and adjacent tissues in the Syrian golden hamster

Mlkvý¹,

Messmann²,

Pauer³

et al. 1996

Br J Cancer

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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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Section: Dis Assimentioning

confidence: 95%

Distribution and photodynamic effects of meso-tetrahydroxyphenylchlorin (mTHPC) in the pancreas and adjacent tissues in the Syrian golden hamster

Mlkvý¹,

Messmann²,

Pauer³

et al. 1996

Br J Cancer

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“…Most tissues have many component parts, but these can be divided broadly into living, functional cells and an underlying scaffold of components like collagen and elastin that are produced by living cells and provide mechanical strength and integrity to an organ, but are not actually living cells. As there is no increase in tissue temperature during PDT, there is little effect on these nonliving connective tissues; as a consequence, the mechanical integrity of hollow organs can be maintained, even if the living cells in all layers of the wall of organs like the gastrointestinal tract or major arteries have been killed [6,7]. In organs like the skin and mouth, this maintenance of the underlying connective tissue encourages healing by regrowth of normal cells on the preserved scaffold, so reducing the risk of scarring.…”

Section: The Biological Effects Of Photodynamic Therapymentioning

confidence: 99%

“…By contrast, local destruction of tissue with heat destroys the connective tissue, which can put the mechanical integrity of hollow organs at risk [6]. …”

Section: The Biological Effects Of Photodynamic Therapymentioning

confidence: 99%

Photodynamic therapy for photochemists

Bown

2013

Phil. Trans. R. Soc. A.

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One contribution of 18 to a Discussion Meeting Issue 'Photoactivatable metal complexes: from theory to applications in biotechnology and medicine' . Photodynamic therapy (PDT) is an evolving technique for localized control of diseased tissue with light after prior administration of a photosensitizing agent and in the presence of oxygen. The biological effect is quite different from surgery, radiotherapy and chemotherapy. With no temperature change during treatment, connective tissues like collagen are largely unaffected, so maintaining the mechanical integrity of hollow organs. PDT is of particular value for precancer and early cancers of the skin (not melanomas) and mouth as the cosmetic and functional results are so good. Another key indication is for small areas of cancer that are unsuitable for or have persisted or recurred after conventional management. It can be applied in areas already exposed to the maximum safe dose of radiotherapy. Outside cancer, in ophthalmology, it is established for agerelated macular degeneration, and has considerable potential in arterial disease for preventing restenosis after balloon angioplasty and in the treatment of infectious diseases, where the responsible organisms are accessible to both the photosensitizer and light. New developments on the horizon include techniques for increasing the selectivity for cancers, such as coupling photosensitizers to antibodies, and for stimulating immunological responses, but many further pre-clinical and clinical studies are needed to establish PDT's role in routine clinical practice.

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“…It involves administration of a photosensitising drug followed by delivery of light of an appropriate wavelength to the target area to produce tissue destruction by photochemical mechanisms (Foote, 1976). In a range of organs it has been shown to destroy glandular tissue (normal or neoplastic) with little effect on connective tissue, and healing mainly by regeneration rather than scarring (Barr et al, 1987). This makes it an attractive option for treating localised prostate cancer, since it has the potential to destroy malignant tissue in the prostate in situ with safe healing of necrosis in normal and neoplastic areas without destroying the connective tissue structure of the gland.…”

mentioning

confidence: 99%

Interstitial and transurethral photodynamic therapy of the canine prostate using meso-tetra-(m-hydroxyphenyl) chlorin

et al. 1996

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Photodynamic therapy (PDT) produces localised necrosis with light after prior administration of a photosensitising drug. Although the technique is promising for small tumours of hollow organs, little work has been done on solid organs like the prostate. We studied the tissue biodistribution and photodynamic effects of meso-tetra-(m-hydroxyphenyl) chlorin (mTHPC), a potent second-generation photosensitiser, on normal canine prostate in vivo. Using quantitative fluorescence microscopy, the highest concentration of mTHPC in the prostate was seen 24-72 hr after intravenous administration. For PDT, red light (650 nm) was delivered to the prostate by laser fibres inserted via the transurethral or transperineal route under transrectal ultrasound guidance. PDT lesions up to 40 mm in diameter (using 4 fibre sites) were produced, characterised by swelling, inflammatory response and extensive glandular destruction. There was persistent glandular atrophy at 90 days, but no disruption of the main stroma and no change in the ultimate size or shape of the gland. Urethral damage sometimes caused temporary urinary retention, but this resolved by 7 days, and no animal became incontinent. Occasional small lesions were seen in the rectum, but these healed without sequelae and there were no fistulae. Since cancer and normal prostate are likely to respond similarly, PDT has considerable promise for treating cancer confined to the gland as large areas of glandular tissue can be necrosed with safe healing. Because the structural integrity of the gland is maintained, PDT is unlikely to be of value in the management of benign prostatic hypertrophy.o 1996 Wiley-Li,m, Inc.

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THE CONTRASTING MECHANISMS OF COLONIC COLLAGEN DAMAGE BETWEEN PHOTODYNAMIC THERAPY and THERMAL INJURY

Cited by 124 publications

References 9 publications

Distribution and photodynamic effects of meso-tetrahydroxyphenylchlorin (mTHPC) in the pancreas and adjacent tissues in the Syrian golden hamster

Distribution and photodynamic effects of meso-tetrahydroxyphenylchlorin (mTHPC) in the pancreas and adjacent tissues in the Syrian golden hamster

Photodynamic therapy for photochemists

Interstitial and transurethral photodynamic therapy of the canine prostate using meso-tetra-(m-hydroxyphenyl) chlorin

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