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S G Bown

Publications and source records attributed to S G Bown.

At least 37 records · Page 2Linked to original sources
PubMed2000

The biology of photodynamic therapy in the gastrointestinal tract.

This article reviews current knowledge on the biology of photodynamic therapy on normal and diseased tissues in the gastrointestinal tract. There is little effect on connective tissue, so the mechanical integrity of the luminal gut is well preserved, even with full thickness damage. This makes photodynamic therapy suitable for treating small tumors, but strictures may occur after circumferential treatment of conditions like Barrett's esophagus unless a muscle-sparing photosensitizing agent is used. Animal studies show that the pancreas and surrounding tissues can tolerate photodynamic therapy, justifying pilot clinical trials on percutaneous, interstitial photodynamic therapy for localized, inoperable pancreatic cancers.

Animals↗
PubMed2000

Optical biopsy systems for the diagnosis and monitoring of superficial cancer and precancer.

Histopathology is the gold standard in the diagnosis of cancer and dysplasia. Screening for the disease in high-risk populations(6,15) and choosing the correct site for biopsy have implications for the choice of follow-up intervals and therapy. Sully & Field(12) suggest that molecular genetic analysis, such as the polymerase chain reaction, for detecting progressive loss of heterozygosity, may be a more accurate predictor of the clinical course of oral cancer. This technique is now semi-automated and compares favourably with the time taken for histopathology (commonly 1-2 weeks). Recent developments suggest that the fluorescent and spectroscopic features may distinguish diseased from healthy tissue, and below follows an introduction for the clinician to this fascinating and complex field. It is possible to obtain a diagnosis in real-time and, with the appropriate use of photochemicals and image enhancement, it may be possible to treat and monitor the effects of treatment in real-time.

Biopsy↗
PubMed1999

Clinical study of adjuvant photodynamic therapy to reduce restenosis following femoral angioplasty.

BACKGROUND: Photodynamic therapy (PDT) reduces neointimal hyperplasia and negative remodelling following balloon injury in small and large animal models. This clinical study investigated the role of adjuvant PDT following femoral percutaneous transluminal angioplasty (PTA). METHODS: Eight PTAs in seven patients (two women) with a median age of 70 (range 59-86) years were performed with adjuvant PDT. All patients had previously undergone conventional angioplasty at the same site which resulted in symptomatic restenosis or occlusion between 2 and 6 months. Each was sensitized with oral 5-aminolaevulinic acid 60 mg/kg, 5-7 h before the procedure. Following a second femoral angioplasty, up to 50 J/cm2 red light (635 nm) was delivered to the angioplasty site via a laser fibre within the angioplasty balloon. Patients were kept in subdued light overnight and discharged the following day. Outcome was assessed by duplex imaging at 24 h, 1, 3 and 6 months and by intravenous digital subtraction angiography at 6 months. A peak systolic velocity ratio (PSVR) of more than 2.0 at the angioplasty site was taken to represent restenosis. RESULTS: All patients tolerated the procedure well without adverse complications or death. All were rendered asymptomatic which was sustained throughout the study interval. All vessels remained patent and no lesion attained the duplex definition of restenosis. Median (interquartile range) PSVR across stenotic segments was 4.7 (3.7-5.7) before angioplasty, 1.1 (0.9-1.3) at 24 h and 1.4 (1.0-1.8) at 6 months after intervention (P = 0.04 compared with preoperative value). CONCLUSION: This pilot study suggests that endovascular PDT is safe and may reduce restenosis follow- ing angioplasty. The data justify a randomized controlled trial.

Aged↗
PubMed1999

Near-infrared optical properties of ex vivo human uterus determined by the Monte Carlo inversion technique.

The optical properties, absorption (mua) and reduced scattering coefficient (mu's), of ex vivo human myometrium and leiomyoma (fibroid) have been determined by the Monte Carlo inversion technique over the wavelength range 600-1000 nm. This region is currently of interest for new, minimal-access, surgical laser procedures such as photodynamic therapy (PDT) for abnormalities of the uterus, and interstitial laser photocoagulation (ILP) for the thermal ablation of fibroids. In the region 630-675 nm (corresponding to PDT), the optical coefficients of myometrium are mua = 0.041+/-0.012 mm(-1) and mu's = 1.37+/-0.19 mm(-1). For the wavelength range 800-1000 nm (associated with infrared lasers for ILP), the optical coefficients of fibroid were found to be mua = 0.020+/-0.003 mm(-1) and mu's = 0.56+/-0.03 mm(-1). Overall, the optical properties of fibroid were found to be lower than myometrium, and this was attributed to the differences in both anatomy and vascularity. The results show that PDT for ablation of the uterine endometrium is most unlikely to affect any tissues beyond the myometrium, and that the region around 800 nm is the most effective for ablation of fibroids using ILP as the penetration depth of light is greatest at this wavelength.

Adult↗
PubMed1999

New photosensitizers for photodynamic therapy in gastroenterology.

Most applications of photodynamic therapy (PDT) in gastroenterology to date have used porfimer sodium as the photosensitizing agent. For destroying small lesions in the wall of the gastrointestinal tract in inoperable patients, it has proved to be most effective, but attempts to achieve circumferential mucosal ablation, as in the treatment of Barrett's esophagus, have led to a high incidence of strictures, and all patients have cutaneous photosensitivity, which can last up to three months. Two new photosensitizers are of particular interest to gastroenterologists. PDT with metatetrahydroxyphenyl chlorin produces a similar biological effect as PDT with porfimer sodium, but the light doses required are much smaller, and cutaneous photosensitivity lasts only two to three weeks. Further, it can be used with percutaneous light delivery to destroy localized pancreatic cancers. The photosensitizing agent 5-amino levulinic acid, converted in vivo into the photoactive derivative protoporphyrin IX, sensitizes the mucosa much more than the underlying layers. This makes it feasible to destroy areas of abnormal mucosa without damaging the underlying muscle and is, therefore, better for treating Barrett's esophagus. Detailed clinical studies are required to establish the real role of PDT with the use of these and other new photosensitizers.

Aminolevulinic Acid↗
PubMed1999

Fine-needle interstitial photodynamic therapy of the lung parenchyma: photosensitizer distribution and morphologic effects of treatment.

STUDY OBJECTIVE: To look at the effect of interstitial photodynamic therapy (PDT) in normal lung parenchyma to assess its potential for treating localized, peripheral lung tumors. DESIGN: Studies were performed on normal Wistar rats using the photosensitizer meso-tetrahydroxyphenyl chlorine. Drug distribution was measured by fluorescence microscopy on tissue sections. Light was delivered to the lungs via a single fiber inserted percutaneously under x-ray control and the PDT effect studied in animals killed at times up to 6 months later. RESULTS: Fluorescence studies showed that the drug was initially distributed throughout the lung, but was later predominantly in the vasculature, bronchi, and macrophages. PDT produced sharply defined zones of hemorrhagic necrosis up to 12 mm in diameter that healed with regeneration of bronchial epithelium and local fibrosis. Different histologic effects were seen between drug light intervals of 1 and 3 days. Treatment was well tolerated, there was a low incidence of pneumothorax, and as long as the fiber tip was within the lung parenchyma, there was no damage to adjacent tissues. CONCLUSION: Interstitial PDT produces zones of necrosis in normal lung that heal safely by a percutaneous technique without affecting adjacent areas of untreated lung. If the lesion size can be increased by using multiple fibers, this could be a promising new technique for treating localized, peripheral lung cancers in patients who are unfit for surgery.

Animals↗
PubMed1999

Light dose fractionation to enhance photodynamic therapy using 5-aminolevulinic acid in the normal rat colon.

5-Aminolevulinic acid (ALA) is an attractive photosensitizing agent for photodynamic therapy (PDT) as its photoactive derivative, protoporphyrin IX, is metabolized within 1-2 days, eliminating prolonged skin photosensitivity. However, at the maximum dose patients can tolerate by mouth, 60 mg/kg, only superficial effects are seen. This paper extends earlier studies on enhancing the effect by light fractionation. Experiments in the normal rat colon looked at the area of necrosis around a single light delivery fiber 3 days after PDT with a range of light-dose fractionation regimes. All animals were given 200 mg/kg ALA intravenously 2 h prior to light delivery (100 mW at 635 nm) and each interruption in illumination was for 150 s. The area of PDT necrosis (total dose 25 J) could be increased by a factor of 3 with a single interval after 5 J, compared with continuous illumination. Alternatively, with this single break, the total light dose could be reduced by 60% to achieve the same area of necrosis as with continuous illumination. This simple modification to PDT with ALA could markedly reduce current treatment times as well as increasing clinical efficacy.

Aminolevulinic Acid↗
PubMed1998

Spatial measurement of oxygen levels during photodynamic therapy using time-resolved optical spectroscopy.

Tissue oxygenation is one of the key dosimetric factors involved in the application of photodynamic therapy (PDT). However, quantitative studies of oxygenation levels at and surrounding the treatment site have been lacking both before, during and after treatment. With the recent development of sensitive, non-invasive, optical spectroscopic techniques based on oxygen-dependent phosphorescence quenching of probe compounds, oxygenation levels can now be measured quantitatively at selected sites with spatial resolution on the millimeter scale. We present results using the phosphorescent compound, palladium meso-tetra(carboxyphenyl)porphine, for measurement of in vivo microvascular oxygen tensions in rat liver during PDT. Time-resolved phosphorescence detection was carried out using fibre-optic sensoring, and oxygen tensions were determined from the phosphorescence lifetimes using Stern-Volmer analysis. During PDT treatment using 5-aminolaevulinic (ALA) acid-induced protoporphyrin IX (PPIX) with a 50 mg/kg ALA dose, oxygen levels near the irradiation fibre placed on the surface of the liver showed a significant decrease by a factor of ten from 20 to 2 torr after an energy dose of 60 J using 100 mW at 635 nm. Areas farther from the treatment site which were exposed to lower light doses exhibited lower reductions in oxygen levels. This spectroscopic technique is a highly sensitive means of investigating tissue oxygenation during and after treatment, and should help not only to advance the understanding of hypoxia and microvascular damage in the PDT mechanism but also contribute to improving the dosimetry of PDT.

Aminolevulinic Acid↗
PubMed1998

Intra-arterial photodynamic therapy using 5-ALA in a swine model.

OBJECTIVES: To test the hypothesis that intravascular light could be delivered via a balloon catheter for arterial photodynamic therapy (PDT). DESIGN: Pig non-injury model. MATERIALS: Clinical catheter equipment. METHODS: Large White pigs (15-20 micrograms) were photosensitised with 5-aminolaevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) at a concentration of 120 mg/kg. Arterial biopsies were taken at intervals between 30 mins and 24 h and frozen sections analysed using a CCD camera to give a temporal profile of fluorescence in each arterial layer. PDT was given to normal arterial segments via a 4 mm transparent PTA balloon inflated so as to occlude flow, but not distend the artery. Animals were culled at 3 and 14 days and the above segments harvested. RESULTS: Fluorescence peaked in the adventitia, intima and medial layers at 1.5, 4 and 6 h respectively. PDT at all time points produced VSMC depletion compared with controls. The degree of depletion mirrored the fluorescence profile of PpIX. CONCLUSIONS: PDT can be delivered via a standard PTA balloon with a transparent channel. This depletes the VSMC population within the arterial wall without complications. Intra-arterial PDT is therefore a potential therapy to reduce the incidence of restenosis post-angioplasty.

Aminolevulinic Acid↗
PubMed1998

Enhancement of 5-aminolaevulinic acid-induced photodynamic therapy in normal rat colon using hydroxypyridinone iron-chelating agents.

Currently, the clinical use of 5-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PPIX) for photodynamic therapy (PDT) is limited by the maximum tolerated oral ALA dose (60 mg kg(-1)). This study investigates whether hydroxypyridinone iron-chelating agents can be used to enhance the tissue levels of PPIX, without increasing the administered dose of ALA. Quantitative charge-coupled device (CCD) fluorescence microscopy was employed to study PPIX fluorescence pharmacokinetics in the colon of normal Wistar rats. The iron chelator, CP94, when administered with ALA was found to produce double the PPIX fluorescence in the colonic mucosa, compared with the same dose of ALA given alone and to be more effective than the other iron chelator studied, CP20. Microspectrofluorimetric studies demonstrated that PPIX was the predominant porphyrin species present. PDT studies conducted on the colonic mucosa showed that the simultaneous administration of 100 mg kg(-1) CP94 i.v. and 50 mg kg(-1) ALA i.v. produced an area of necrosis three times larger than similar parameters without the iron-chelating agent with the same light dose. It is possible, therefore, to increase the amount of necrosis produced by ALA-induced PDT substantially, without increasing the administered dose of ALA, through the simultaneous administration of the iron-chelating agent, CP94.

Aminolevulinic Acid↗
PubMed1998

Interstitial laser photocoagulation of normal lung parenchyma in rats.

BACKGROUND: Management of peripheral lung tumours may be risky in patients with poor lung function or in the elderly. A new possibility is interstitial laser photocoagulation (ILP) in which tumours are gently coagulated using thin laser fibres placed percutaneously under radiological guidance. This could have a useful palliative role in selected patients, but to be safe the effects on normal lung parenchyma must first be understood. This paper describes the creation and healing of ILP lesions in the normal rat lung. METHODS: ILP was performed using single laser fibres placed percutaneously in the left lung of normal rats under general anaesthetic with radiological guidance (laser power 1-3 W at 805 nm, treatment time 250-1000 s). The lesion size and healing were studied in rats killed at times from three days to six months after treatment, the bursting pressure was measured, and any complications noted. RESULTS: Zones of necrosis up to 12 mm in diameter were produced, the size depending on the laser power and treatment time. Histological examination showed typical thermal effects with complete healing with fibrosis by two months. The effect was very localised with remarkably little effect on the structure and function of the rest of the lung. Adverse effects in the lung parenchyma only occurred if the ILP lesion involved the hilar vessels or the oesophagus, causing pulmonary congestion and perforation, respectively. Pneumothorax was seen in 6% of cases. CONCLUSIONS: ILP with a single fibre can produce a localised zone of necrosis in normal lung parenchyma which heals safely and which has little effect on the rest of the lung. Further study of this technique using multiple fibres in a larger animal model is warranted to see if it is feasible and safe to produce a large enough volume of necrosis to be of value in the treatment of small peripheral lung tumours in patients who are unsuitable for surgery or palliative radiotherapy.

Animals↗
PubMed1998

Photodynamic therapy for gastrointestinal tumors using three photosensitizers--ALA induced PPIX, Photofrin and MTHPC. A pilot study.

Photodynamic therapy (PDT) produces localized necrosis with light after prior administration of a photosensitizing drug. As PDT lesions in the gastrointestinal tract heal well, the technique is suitable for repeated endoscopic use. In this study we used PDT to treat benign and malignant gastrointestinal tumors in esophagus, duodenum and rectum in 22 patients, who refused or were not suitable for surgery. Patients were sensitized with 0.15 mg/kg of body weight with mesotetrahydroxyphenylchlorin i.v. m-THPc (2 patients), with 2.0 mg/kg Photofrin i.v. (4 patients) or 60 mg/kg 5-aminolevulinic acid orally ALA (which is converted in vivo to active derivate protoporphyrin IX-PRIX) in fractionated doses (16 patients). Laser treatment was performed 2 days after Photofrin, 2 and 4 days after mTHPc and 4 hours after ALA, using a metal vapour laser (628 nm, 50-150 J/cm2 for ALA and Photofrin, 650 nm and 10-15 J/cm2 for mTHPc). Using ALA, the necrosis was only superficial (up to 1.8 mm depth). Four patients treated with Photofrin showed deeper necrosis, in one case of 8 mm colon cancer complete response, in three cases 1-1.5 cm adenomatous polyps involving the ampulla Vateri 50% longer term reduction in size-seen endoscopically. Two patients with rectal villous adenomas treated with mTHPc showed 60-80% reduction in size (observed endoscopically) within few days after PDT, with better effects for treatment carried out 4 rather than 2 days after the sensitization. In all patients the healing was without any complications. Photofrin and mTHPc work better, but cause cutaneous photosensitivity lasting 12 and 5 weeks, respectively. Better results with ALA are possible when using higher drug doses or modified light dosimetry. PDT is a promising treatment for small localized tumors in patients unsuitable for surgery, but further work is required to optimize the treatment conditions.

Adult↗
PubMed1997

Photodynamic therapy using mTHPC for malignant disease in the oral cavity.

Photodynamic therapy (PDT) produces local tumor necrosis, on activation of a previously administered sensitizer with non-thermal light of an appropriate wavelength. It is attractive for treating tumors of the mouth as tissue healing is particularly good. We describe the use of the photosensitizing agent meta tetrahydroxyphenyl chlorin (mTHPC, Foscan) for PDT of oral cancer, including patients with field cancerization. Nineteen patients with histologically confirmed oral cancer (8 with field change disease) and one with severe dysplasia, were sensitised with mTHPC intravenously. Activation was carried out 72-96 hr later with laser light at 652 nm using a range of light doses. The results were assessed clinically and histologically. Multiple biopsies were taken during the ulcerative stages to look at the effects of PDT and after healing to assess the overall treatment result. All single lesions up to stage T3 cleared after one PDT treatment (total of 6 patients). Three out of 6 T4 tumours were also cleared. Lesions in patients with field change disease did less well, only 9 of 14 T1 and T2s clearing, including 4 that required extra treatments with a higher light dose. Most healed very well, but tongue tethering was seen in 1 patient and another had necrosis in normal areas due to light scattering within the mouth. PDT using mTHPC is a promising new treatment for patients with oral cancer.

Adult↗
PubMed1997

Interstitial photodynamic therapy in the canine prostate with disulfonated aluminum phthalocyanine and 5-aminolevulinic acid-induced protoporphyrin IX.

BACKGROUND: Photodynamic therapy (PDT) is an experimental approach for treating prostate cancer localized to the gland that does not involve surgery or irradiation. Second-generation photosensitizers 5-aminolevulinic acid (ALA) and aluminum disulfonated phthalocyanine (AlS2Pc) were studied in the normal canine prostate. METHODS: Tissue biodistribution of photosensitizers on serial biopsies was examined using fluorescence microscopy. Photodynamic therapy was done by delivering red light interstitially at 100 mW through fibers placed under transrectal ultrasound guidance. RESULTS: Peak levels of AlS2Pc appeared at 5-24 hr and at 3 hr for ALA. Macroscopic PDT lesions were up to 12 mm in diameter using AlS2Pc, but only 1-2 mm with ALA. Light at 300 mW caused thermal lesions. At 28 days, damaged glands remained atrophic, but the interlobular supporting stroma was well-preserved. Urethral lesions healed by 28 days without functional impairment. CONCLUSIONS: Although the results with ALA were disappointing, PDT using AlS2Pc looks like a promising modality for treatment of localized prostate cancer.

Aminolevulinic Acid↗
PubMed1997

Photodynamic therapy: an effective, but non-selective treatment for superficial cancers of the oral cavity.

It has often been claimed that photodynamic therapy (PDT) produces selective destruction of small cancers without affecting the adjacent normal tissue. The objective of our work was to treat small cancers of the oral cavity with PDT and subsequently excise the treated areas for histological studies of tumour and adjacent normal tissue exposed to the same light dose. Eleven patients with histologically proven T1NO oral squamous-cell carcinomas were treated with PDT, using Photofrin as a sensitiser. The tumours plus a surrounding cuff of normal tissue were exposed to 50 J/cm2 non-thermal laser light at 630 nm delivered by surface illumination and the treated areas subsequently excised. Histological staining and image analysis were used to determine the nature and extent of injury. No macroscopic distinction was evident between tumour and normal tissue exposed to light. Histologically, replacement of superficial epithelium, tumour and connective tissue with a fibrinous necrotic slough was seen. There was also loss of endothelium from small vessels, with haemorrhage and thrombosis. Preservation of subepithelial collagen and elastin was demonstrated with EVG staining. No evidence of selective tumour necrosis was found. Although depth of injury was variable, full thickness mucosal necrosis occurred in all cases.

Carcinoma, Squamous Cell↗
PubMed1997

5-Aminolevulinic acid (ALA)-induced protoporphyrin IX fluorescence and photodynamic effects in the rat bladder: an in vivo study comparing oral and intravesical ALA administration.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) for sensitization is a promising treatment for carcinoma in situ and diffuse premalignant changes of the bladder. We studied the biodistribution of PpIX in a range of tissues with oral and intravesical routes of administration of ALA and compared the photodynamic effects on bladder and skin. STUDY DESIGN/MATERIALS AND METHODS: Normal Wistar rats were given oral or intravesical ALA and PpIX levels in the liver, kidney, skin, and bladder measured by fluorescence microscopy on tissue sections. At the time of maximum PpIX levels, the bladder and skin on the back were illuminated with light at 630 nm and the PDT effects compared. RESULTS: PpIX fluorescence in the urothelium after 200 mg/kg given intravesically was comparable to that found after 100 mg/kg orally. The ratio of PpIX levels between the urothelium and the underlying muscle was the same for both routes of administration, although there appeared to be more selectivity of urothelial PDT necrosis after intravesical administration. Skin photosensitization was greater after oral ALA, the epidermal PpIX level being three times higher than after intravesical administration for comparable urothelial levels and the PDT effect being more marked. CONCLUSIONS: Intravesical instillation is preferable to oral administration of ALA for PDT ablation of the urothelium of the rat bladder without damage to the underlying tissue layers and for minimizing skin photosensitivity. The technique is now ready for clinical trials.

Administration, Intravesical↗