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S G Bown

Publications and source records attributed to S G Bown.

At least 19 recordsLinked to original sources
PubMed2006

Elastic scattering spectroscopy accurately detects high grade dysplasia and cancer in Barrett's oesophagus.

BACKGROUND AND AIMS: Endoscopic surveillance of Barrett's oesophagus currently relies on multiple random biopsies. This approach is time consuming, has a poor diagnostic yield, and significant interobserver variability. Elastic scattering spectroscopy is a real time in vivo optical technique which detects changes in the physical properties of cells. The aim of this study was to assess the potential for elastic scattering to detect high grade dysplasia or cancer within Barrett's oesophagus. METHODS: Elastic scattering spectroscopy measurements collected in vivo were matched with histological specimens taken from identical sites within Barrett's oesophagus. All biopsies were reviewed by three gastrointestinal pathologists and defined as either "low risk" (non-dysplastic or low grade dysplasia) or "high risk" (high grade dysplasia or cancer). Two different statistical approaches (leave one out and block validation) were used to validate the model. RESULTS: A total of 181 matched biopsy sites from 81 patients, where histopathological consensus was reached, were analysed. There was good pathologist agreement in differentiating high grade dysplasia and cancer from other pathology (kappa = 0.72). Elastic scattering spectroscopy detected high risk sites with 92% sensitivity and 60% specificity and differentiated high risk sites from inflammation with a sensitivity and specificity of 79%. If used to target biopsies during endoscopy, the number of low risk biopsies taken would decrease by 60% with minimal loss of accuracy. A negative spectroscopy result would exclude high grade dysplasia or cancer with an accuracy of >99.5%. CONCLUSIONS: These preliminary results show that elastic scattering spectroscopy has the potential to target conventional biopsies in Barrett's surveillance saving significant endoscopist and pathologist time with consequent financial savings. This technique now requires validation in prospective studies.

Adenocarcinoma↗
PubMed2006

Photodynamic therapy using meso tetra hydroxy phenyl chlorin (mTHPC) in early prostate cancer.

BACKGROUND AND OBJECTIVES: Prostate cancer is increasing in incidence, but current treatments including surgery and radiotherapy have significant side effects. This pilot study was designed to assess the potential of photodynamic therapy (PDT) using meso tetra hydroxy phenyl chlorin (mTHPC) for organ confined prostate cancer. STUDY DESIGN/PATIENTS AND METHODS: Six men with organ confined prostate cancer were photosensitised with mTHPC (0.15 mg/kg). Between 2 and 5 days later, red light (652 nm) was delivered to areas of biopsy proven cancer via fibres inserted through transperineal needles (50-100 J per site). RESULTS: After 8 of 10 PDT sessions, the prostate specific antigen (PSA) fell by up to 67%. Early MRI scans showed oedema and patchy necrosis, which resolved over 2 months. Biopsies of treated areas revealed necrosis and fibrosis at 1-2 months. CONCLUSIONS: PDT for primary prostate cancer appears safe and can reduce PSA levels. As this was a phase I study, no attempt was made to treat the whole prostate; this or targeted tumour ablation could be attempted in a phase II study with an increased number of fibres. This technique merits further investigation in early prostate cancer.

Aged↗
PubMed2004

Correlation of real-time haemoglobin oxygen saturation monitoring during photodynamic therapy with microvascular effects and tissue necrosis in normal rat liver.

Photodynamic therapy (PDT) requires a photosensitising drug, light and oxygen. While it is known that the haemoglobin oxygen saturation (HbSat) can be altered by PDT, little has been done to correlate this with microvascular changes and the final biological effect. This report describes such studies on the normal liver of rats sensitised with aluminium disulphonated phthalocyanine. In total, 50 J of light at 670 nm, continuous or fractionated at 25 or 100 mW, was applied with a single laser fibre touching the liver surface. HbSat was monitored continuously 1.5-5.0 mm from the laser fibre using visible light reflectance spectroscopy (VLRS). Vascular shutdown was assessed by fluorescein angiography 2-40 min after light delivery. Necrosis was measured at post mortem 3 days after PDT. In all treatment groups at a 1.5 mm separation, HbSat fell to zero with little recovery after light delivery. At 2.5 mm, HbSat also decreased during light delivery, except with fractionated light, but then recovered. The greatest recovery of fluorescein perfusion after PDT was seen using 25 mW, suggesting an ischaemia/reperfusion injury. Necrosis was more extensive after low power and fractionated light than with 100 mW, continuous illumination. We conclude that VLRS is a useful technique for monitoring HbSat, although the correlation between HbSat, fluorescein exclusion and necrosis varied markedly with the light delivery regimen used.

Animals↗
PubMed2004

Interstitial photodynamic therapy as salvage treatment for recurrent head and neck cancer.

Interstitial photodynamic therapy (IPDT) is a technique for applying photodynamic therapy (PDT) to internal tumours using light delivered via fibres inserted percutaneously. This phase I-II study assessed the safety and efficacy of IPDT for patients with persistent or recurrent head and neck cancer unsuitable for further treatment with surgery, radiotherapy or chemotherapy, recruited for 'last hope' salvage treatment. Patients were sensitised with 0.15 mg kg(-1) mTHPC (meso-tetrahydroxyphenyl chlorin) 4 days prior to light delivery from fibres inserted directly into the target tumour (20 J per site at 652 nm) under image guidance. In all, 45 patients were treated. Nine achieved a complete response. Five are alive and free of disease 10-60 months later. Symptomatic relief (mainly for bleeding, pain or tumour debulking) was achieved in a further 24. The median survival (Kaplan-Meier) was 16 months for the 33 responders, but only 2 months for the 12 nonresponders. The only serious complication was a carotid blow out 2 weeks after PDT. No loss of function was detected in nerves encased by treated tumours. Interstitial photodynamic therapy provides worthwhile palliation with few complications and occasional long-term survivors for otherwise untreatable advanced head and neck cancers. It is a treatment option worth adding to those available to integrated head and neck oncology teams.

Adolescent↗
PubMed2004

Nd:YAG laser induces long-term remission in transfusion-dependent patients with watermelon stomach.

Watermelon stomach (gastric antral vascular ectasia) is a rare cause of gastric bleeding which can render patients transfusion-dependent. Laser therapy can be used to stop bleeding but the long-term success of this approach is not well described. We present a retrospective analysis of 24 consecutive transfusion-dependent patients who were treated in a national referral centre with Nd:YAG laser over an 18 year period. Laser therapy stopped all bleeding in 20 patients (83%) after a median of two sessions. Median follow up was 55 months (range 9-127). Patients remained transfusion free for a median of 16 months and a second course of treatment succeeded in all those who re-bled. One gastric perforation occurred early in the series and two patients developed pyloric stenosis which was successfully treated with balloon pyloric dilatation. Oestrogens were not used in these patients. Our experience shows that long-term remission from blood transfusion is seen in most patients treated with Nd:YAG laser. If bleeding recurs, further laser treatment is usually successful.

Adult↗
PubMed2002

The role of reperfusion injury in photodynamic therapy with 5-aminolaevulinic acid--a study on normal rat colon.

Reperfusion injury can occur when blood flow is restored after a transient period of ischaemia. The resulting cascade of reactive oxygen species damages tissue. This mechanism may contribute to the tissue damage produced by 5-aminolaevulinic acid-induced photodynamic therapy, if this treatment temporarily depletes oxygen in an area that is subsequently reoxygenated. This was investigated in the normal colon of female Wistar rats. All animals received 200 mg kg(-1) 5-aminolaevulinic acid intravenously 2 h prior to 25 J (100 mW) of 628 nm light, which was delivered continuously or fractionated (5 J/150 second dark interval/20 J). Animals were recovered following surgery, killed 3 days later and the photodynamic therapy lesion measured macroscopically. The effects of reperfusion injury were removed from the experiments either through the administration of free radical scavengers (superoxide dismutase (10 mg kg(-1)) and catalase (7.5 mg kg(-1)) in combination) or allopurinol (an inhibitor of xanthine oxidase (50 mg kg(-1))). Prior administration of the free radical scavengers and allopurinol abolished the macroscopic damage produced by 5-aminolaevulinic acid photodynamic therapy in this model, regardless of the light regime employed. As the specific inhibitor of xanthine oxidase (allopurinol) protected against photodynamic therapy damage, it is concluded that reperfusion injury is involved in the mechanism of photodynamic therapy in the rat colon.

Allopurinol↗
PubMed2002

Optimisation of illumination for photodynamic therapy with mTHPC on normal colon and a transplantable tumour in rats.

Recent reports suggest that the effect of photodynamic therapy (PDT) can be enhanced by fractionating the light dose or reducing the light fluence rate. We assessed these options on two tissues in rats (normal colon and a transplanted fibrosarcoma) using the photosensitiser meta-tetrahydroxyphenylchlorin (mTHPC). Animals were sensitised with 0.3 mg/kg mTHPC, 3 days prior to illumination with red light (652 nm) using a single fibre touching the target tissue and killed 1-3 days later for quantitative measurement of the extent of PDT necrosis. Results were similar for both tissues, although the differences between illumination regimens were less marked in tumour tissue. Using continuous illumination and a fixed low energy in colon, the extent of necrosis was up to almost three times larger with 5 mW than with 100 mW, although the maximum attainable necrosis was independent of power. The long treatment time using 5 mW could be halved without loss of effect by increasing the power during treatment. Dividing the light into two equal fractions at 100 mW increased the lesion size by up to 20% in colon (independent of the timing of the dark interval), but by only 10% in tumour and had no effect at 20 mW. Previous studies using 5-aminolaevulinic acid (ALA) showed a much larger effect of fractionation that was critically dependent on the timing of the dark interval. We postulate that enhancement of PDT by fractionation is due to improved oxygen supply to the treated area which may be due to reversal of temporary vascular occlusion (more likely with ALA) or less rapid photochemical consumption of oxygen (more likely with mTHPC). At lower fluence rates, the oxygen consumption rate is not fast enough to be improved by fractionation. We conclude that fractionated or low power light delivery can enhance PDT with mTHPC. Although the effects are not large, this may be of value for interstitial treatment of solid tumours when multiple sites are treated simultaneously.

Animals↗
PubMed2002

Laser augmented by brachytherapy versus laser alone in the palliation of adenocarcinoma of the oesophagus and cardia: a randomised study.

BACKGROUND: Many patients with advanced malignant dysphagia are not suitable for definitive treatment. The best option for palliation of dysphagia varies between patients. This paper looks at a simple technique for enhancing laser recanalisation. AIM: To assess the value of adjunctive brachytherapy in prolonging palliation of malignant dysphagia by endoscopic laser therapy. PATIENTS: Twenty two patients with advanced malignant dysphagia due to adenocarcinoma of the oesophagus or gastric cardia, unsuitable for surgery or radical chemoradiotherapy. METHODS: Patients able to eat a soft diet after laser recanalisation were randomised to no further therapy or a single treatment with brachytherapy (10 Gy). Results were judged on the quality and duration of dysphagia palliation, need for subsequent intervention, complications, and survival. RESULTS: The median dysphagia score for all patients two weeks after initial treatment was 1 (some solids). The median dysphagia palliated interval from the end of initial treatment to recurrent dysphagia or death increased from five weeks (control group) to 19 weeks (brachytherapy group). Three patients had some odynophagia for up to six weeks after brachytherapy. There was no other treatment related morbidity or mortality. Further intervention was required in 10 of 11 control patients (median five further procedures) compared with 7/11 brachytherapy patients (median two further procedures). There was no difference in survival (median 20 weeks (control), 26 weeks (brachytherapy)). CONCLUSIONS: Laser therapy followed by brachytherapy is a safe, straightforward, and effective option for palliating advanced malignant dysphagia, which is complementary to stent insertion.

Adenocarcinoma↗
PubMed2002

Photodynamic therapy for cancer of the pancreas.

BACKGROUND: Few pancreatic cancers are suitable for surgery and few respond to chemoradiation. Photodynamic therapy produces local necrosis of tissue with light after prior administration of a photosensitising agent, and in experimental studies can be tolerated by the pancreas and surrounding normal tissue. AIMS: To undertake a phase I study of photodynamic therapy for cancer of the pancreas. PATIENTS: Sixteen patients with inoperable adenocarcinomas (2.5-6 cm in diameter) localised to the region of the head of the pancreas were studied. All presented with obstructive jaundice which was relieved by biliary stenting prior to further treatment. METHODS: Patients were photosensitised with 0.15 mg/kg meso-tetrahydroxyphenyl chlorin intravenously. Three days later, light was delivered to the cancer percutaneously using fibres positioned under computerised tomographic guidance. Three had subsequent chemotherapy. RESULTS: All patients had substantial tumour necrosis on scans after treatment. Fourteen of 16 left hospital within 10 days. Eleven had a Karnofsky performance status of 100 prior to treatment. In 10 it returned to 100 at one month. Two patients with tumour involving the gastroduodenal artery had significant gastrointestinal bleeds (controlled without surgery). Three patients developed duodenal obstruction during follow up that may have been related to treatment. There was no treatment related mortality. The median survival time after photodynamic therapy was 9.5 months (range 4-30). Seven of 16 patients (44%) were alive one year after photodynamic therapy. CONCLUSIONS: Photodynamic therapy can produce necrosis in pancreatic cancers with an acceptable morbidity although care is required for tumours invading the duodenal wall or involving the gastroduodenal artery. Further studies are indicated to assess its influence on the course of the disease, alone or in combination with chemoradiation.

Adenocarcinoma↗
PubMed2001

Interstitial laser photocoagulation and interstitial photodynamic therapy of normal lung parenchyma in the pig.

Interstitial laser photocoagulation (ILP) and interstitial photodynamic therapy (PDT) involve delivery of light to lesions in solid organs using thin fibres passed through needles inserted percutaneously under image guidance. In ILP, the laser energy heats the tissue, whereas in PDT it activates a previously administered photosensitising agent. This study looks at their potential for treating localised, small, peripheral lung cancers in patients unsuitable for surgery. Experiments were undertaken on nine normal pigs, up to four fibres being inserted into the lung parenchyma percutaneously under X-ray guidance (ILP: 2-3 W, 1000 q/fibre, from 805 nm diode laser, PDT, 100-200 J/fibre from 652 nm diode laser at 50-100 W, 3 days after 0.15 mg/kg mTHPC). Animals were killed from 3 days to 3 months later and the treated areas examined macroscopically and microscopically. Both techniques were well tolerated, producing well-defined, localised lesions, typically 3.5 x 2 x 2 cm using four fibres. Histology showed thermal coagulative necrosis after ILP and haemorrhagic necrosis after PDT. Early small haematomas and late cavitation were sometimes seen after ILP, but not after PDT. PDT lesions healed with preservation of larger arteries and bronchi in the treated area. A few small pneumothoraces were seen which resolved spontaneously, probably related to the chest wall puncture. It was concluded that ILP and PDT lesions of a size large enough to cover a small tumour can be made safely in the lung parenchyma, although healing was better after PDT. Pilot clinical studies with both techniques are now justified on carefully selected patients.

Animals↗
PubMed2000

Reduction in the response to coronary and iliac artery injury with photodynamic therapy using 5-aminolaevulinic acid.

OBJECTIVE: Photodynamic therapy (PDT) uses red light (non-thermal, non-ionising) to activate a previously administered photosensitizing drug. This inhibits neointimal hyperplasia in injured arteries in small animals where it appears safe and well tolerated. Our aim was to develop a method for percutaneous application of PDT to iliac and coronary arteries in a large animal model and investigate its influence on the remodeling and intimal hyperplastic response to balloon injury. METHODS: Studies were undertaken on 13 juvenile Large White-Landrace crossbred pigs (15-20 kg). After intravenous administration of the photosensitizing agent 5-amino laevulinic acid (ALA), the arterial tree was accessed via the left common carotid artery and balloon injuries made by over-distension in both common iliacs (thirteen animals) and one or two main coronary arteries (eight animals). Half the injured sites were then illuminated with red laser light transmitted via the catheter. Animals were culled 28 days later and tissue harvested for histomorphometry. RESULTS: Compared with control injured vessels, PDT treated, balloon injured coronary arteries had a larger lumen (1.4 vs. 0.8 mm2, P = 0.002), larger area within the external elastic lamina (2.8 vs. 2.2 mm2, P = 0.006) and smaller area of neointimal hyperplasia (0.4 vs. 0.7 mm2, P = 0.06), 28 days after intervention. Less neointimal hyperplasia and the absence of negative remodeling resulted in the lumen of PDT-treated, injured segments being the same as that of adjacent reference segments (1.5 vs. 1.6 mm2). Similar trends, but with smaller differences, were seen in the iliac vessels. CONCLUSIONS: Intra-arterial, trans-catheter PDT favourably influences the arterial response to balloon injury in both the coronary and peripheral circulations. This technique offers a promising new approach to restenosis after endovascular procedures.

Aminolevulinic Acid↗
PubMed2000

Oxygen monitoring during 5-aminolaevulinic acid induced photodynamic therapy in normal rat colon. Comparison of continuous and fractionated light regimes.

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). Attempts have been made to enhance this treatment modality without increasing the administered dose of ALA. One way to do this is through light dose fractionation, where the irradiation is interrupted at a particular point for a short period of time. This can produce up to three times more necrosis than with the same light dose delivered without a break. An oxygen microelectrode was employed to study the effect of continuous and fractionated light regimes on the level of oxygen in the colon of normal Wistar rats during ALA PDT. A rapid decline in pO2 occurred close to the irradiation fibre as soon as the light dose commenced. With the fractionated regime, a partial recovery in pO2 was observed during the dark interval which was reversed soon after the second light fraction commenced. We have shown that the level of tissue oxygen at the treatment site is affected differently when the light dose is fractionated, than when continuous illumination is employed. This factor may at least partially explain the difference in outcome of these two treatment regimes. Further, oxygen measurements might prove to be a useful way of monitoring PDT treatments if they can predict whether tissue is likely to be viable following treatment.

Aminolevulinic Acid↗
PubMed2000

Photodynamic therapy of rat bladder and urethra: evaluation of urinary and reproductive function after inducing protoporphyrin IX with 5-aminolaevulinic acid.

OBJECTIVE: To assess the urinary and reproductive function of rats after inducing protoporphyrin IX with 5-aminolaevulinic acid (ALA) and subsequent intraurethral photodynamic therapy (PDT). Materials and methods Twelve female Wistar rats were given ALA orally or intravesically (four each), followed by intraurethral PDT through a 10-mm cylindrical fibre at 100 mW for 500 s (argon laser, 632 nm). Urinary frequency, the number of gestations and histological changes were then evaluated and compared with a group of eight control rats. RESULTS: There was only a slight increase in urinary frequency during the first 2 weeks after PDT in the group given oral ALA, while the same degree of urinary frequency was evident for up to 4 weeks in those given intravesical ALA. Despite the occurrence of urinary incontinence from undefined causes in two rats, reproductive function remained unchanged. There was no histological evidence of damage to the reproductive system adjacent to the bladder. CONCLUSIONS: PDT of the urethra with ALA is relatively safe and carries few risks of inducing permanent urological complications.

Administration, Intravesical↗
PubMed2000

Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results.

We report on the first stages of a clinical study designed to test elastic-scattering spectroscopy, mediated by fiberoptic probes, for three specific clinical applications in breast-tissue diagnosis: (1) a transdermal-needle (interstitial) measurement for instant diagnosis with minimal invasiveness similar to fine-needle aspiration but with sensitivity to a larger tissue volume, (2) a hand-held diagnostic probe for use in assessing tumor/resection margins during open surgery, and (3) use of the same probe for real-time assessment of the "sentinel" node during surgery to determine the presence or absence of tumor (metastatic). Preliminary results from in vivo measurements on 31 women are encouraging. Optical spectra were measured on 72 histology sites in breast tissue, and 54 histology sites in sentinel nodes. Two different artificial intelligence methods of spectral classification were studied. Artificial neural networks yielded sensitivities of 69% and 58%, and specificities of 85% and 93%, for breast tissue and sentinel nodes, respectively. Hierarchical cluster analysis yielded sensitivities of 67% and 91%, and specificities of 79% and 77%, for breast tissue and sentinel nodes, respectively. These values are expected to improve as the data sets continue to grow and more sophisticated data preprocessing is employed. The study will enroll up to 400 patients over the next two years.

Adenocarcinoma↗
PubMed2000

Interstitial laser photocoagulation for the treatment of osteoid osteoma.

We report the results of a prospective study of 23 patients in which interstitial laser photocoagulation (ILP) was used to treat an osteoid osteoma. ILP is a technique in which tumour tissue is destroyed by direct heating using low-power laser light energy delivered by thin (400 microm) optical fibres which are introduced percutaneously into the tumour under image guidance. Pain was evaluated before operation and at the latest follow-up using a visual analogue scale with 0 denoting no pain and 10 the worst pain imaginable. The mean follow-up was for 15 months. The results showed that the mean pain score decreased from 7.5 before operation to 0.95 at the latest follow-up. Fourteen patients had no pain and eight had minor discomfort, not requiring analgesia. One patient required a second procedure because placement of the fibre had not been accurate enough and one developed recurrent symptoms eight months after treatment. All patients were satisfied with the operation because of the rapid resolution of pain, the minimally invasive nature of the procedure, and the fact that there was no postoperative restriction of activity.

Adolescent↗