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Papers by Stephen Bown

Reviews in Gynaecological Practice, 2004

ABSTRACT The conventional surgical treatment for women with symptomatic uterine fibroids is a hys... more ABSTRACT The conventional surgical treatment for women with symptomatic uterine fibroids is a hysterectomy. Hysterectomy guarantees the removal of all uterine fibroids without a risk of recurrence. It also guarantees the cure of symptoms such as menorrhagia and pressure effects and has been shown to be associated with a high degree of patient satisfaction and improved quality of life scores. However, in addition to women who desire fertility, there are a growing number of women who have completed their family who do not wish to undergo a hysterectomy. Uterine conserving surgical methods include myomectomy or fibroid shrinkage either by embolisation/laparoscopic clipping of both uterine arteries or myolysis.This article reviews the surgical alternatives to hysterectomy and analyses the data that is currently available with each method. Laparoscopic interstitial laser photocoagulation of uterine fibroids is a relatively new modality of treatment and is carried out in our centre. Results of this method are presented and discussed in this article.Myomectomy is associated with significant morbidity and difficulty in long term management because of high recurrence rates. Surgical alternatives to myomectomy are still limited to large series in a few centres with a special interest in the procedure developed. Well designed long term studies are required to properly evaluate the efficacy and feasibility of each procedure in normal practice and its effect on infertility.

Proceedings of SPIE - The International Society for Optical Engineering

Comparison of holmium:YSGG versus Nd:YAG in an artificial circulation model. [Proceedings of SPIE... more Comparison of holmium:YSGG versus Nd:YAG in an artificial circulation model. [Proceedings of SPIE 1642, 120 (1992)]. Roy N. Lawrence, Jonathan A. Michaels, Stephen G. Bown. Abstract. The effects of pulsed Holmium:Yttrium ...

Gastroenterology

An unselected consecutive series of 826 patients admitted for acute upper gastrointestinal bleedi... more An unselected consecutive series of 826 patients admitted for acute upper gastrointestinal bleeding underwent urgent endoscopy. Peptic ulcers were found in 402 (49%). Of the 329 ulcer craters that could be fully examined, visible vessels were identified in 156 (47%), other stigmata of recent hemorrhage in 66, and no stigmata of recent hemorrhage in 107. One hundred twenty-nine patients with stigmata of recent hemorrhage (93 of whom had visible vessels) randomly allocated to no endoscopic treatment were observed for evidence of further bleeding. Fifty-four of the 93 patients (58%) with visible vessels rebled, compared with 2 of 36 (6%) with other stigmata of recent hemorrhage. No patient without stigmata of recent hemorrhage rebled. Twenty-seven patients in whom a visible vessel in a gastric ulcer was identified at endoscopy underwent urgent partial gastrectomy because of recurrent bleeding. The vessel identified at endoscopy was found in 26 of 27 resection specimens (96%). The arterial vessel wall protruded above the surface of the ulcer crater in 10 specimens, and clot in continuity with a breach in the vessel wall protruded in a further 10 specimens. Postoperative angiography, when technically possible, showed that the breached artery ran across the base of the ulcer in all of these specimens. Pathological changes were common in the bleeding artery and included arteritis in 24 of 29 (83%) eroded arteries found in these specimens, with aneurysmal dilatation in 14 of 27 (52%) bleeding points that could be fully examined. The ulcer had penetrated to serosa in 13 specimens (45%). The bleeding artery had a mean external diameter of 0.7 mm with a range of 0.1-1.8 mm. This study provides new information about the nature of the bleeding vessel in gastric ulcers, and some of this information is relevant in planning studies of endoscopic therapy for bleeding peptic ulcers. It validates the endoscopic identification of a visible vessel, and confirms that such identification has a high predictive value for the development of recurrent hemorrhage.

Gastroenterology

The drawbacks of monopolar electrocoagulation in the control of gastrointestinal bleeding include... more The drawbacks of monopolar electrocoagulation in the control of gastrointestinal bleeding include tissue adherence, unpredictable energy deposition, and a high incidence of tissue damage. Introduction of a conductive interfacial film of liquid between the monopolar electrode and the bleeding point during electrocoagulation may overcome these drawbacks. A prospective, controlled study was undertaken to evaluate the efficacy and safety of a monopolar electrode in liquid and dry modes when used to coagulate experimental canine bleeding ulcers. All experiments were done in open fashion via a gastrotomy with hand-held electrodes. An analog computer, which could be connected between a standard electrosurgical generator and the electrode, was designed and built to monitor and control the energy delivered to the tissue. Both liquid and dry electrodes were highly effective in stopping bleeding. The liquid electrode was found to be superior to the dry electrode in that tissue adherence was eliminated and energy deposition was more predictable, varying less with angle of incidence. The liquid electrode caused less macroscopic serosal damage and less full-thickness histologic damage if the total energy or number of pulses was limited; however, both caused microscopic full-thickness damage in one-half of the experimental ulcers treated, although no perforations occurred.

Photodiagnosis and Photodynamic Therapy, 2011

administration of 5-aminolevulinic acid (ALA). Porphyrin levels in urine were determined for norm... more administration of 5-aminolevulinic acid (ALA). Porphyrin levels in urine were determined for normal and tumor-bearing mice administered with ALA. Both uroporphyrin (UP) and coproporphyrin (CP) levels in urine at 3 h after ALA administration were significantly higher in tumor-bearing than in normal mice. Some porphyrin isomers differed in distribution between normal and tumor-bearing mice. Since no porphyrin level differences were observed without ALA administration, abnormal porphyrin metabolism in tumor cells could influence the porphyrin levels and isomer distributions. These data suggest that porphyrin-based cancer screening may be made possible with ALA administration.

Advances in experimental medicine and biology, 2003

Photodynamic therapy (PDT) is a treatment for various malignant and benign lesions using light-ac... more Photodynamic therapy (PDT) is a treatment for various malignant and benign lesions using light-activated photosensitising drugs in the presence of molecular oxygen. PDT causes tissue damage by a combination of processes involving the production of reactive oxygen ...

Photodiagnosis and Photodynamic Therapy, 2011

Poster Abstracts 187 species (ROS). Depending on the type of cells, photosensitizer and light dos... more Poster Abstracts 187 species (ROS). Depending on the type of cells, photosensitizer and light doses, PDT has been shown to induce cell apoptosis, necrosis and autophagy. PDT is also known to activate cell survival pathways. The final PDT outcome is dependent on the interplay between PDT-induced cell death and survival signals. One of the most important cell survival signals is mediated through phosphatidylinositol 3-kinase (PI3K) pathway. This study focused on understanding the effects of PDT on PI3K pathway and how the interaction between PDT and PI3K pathway inhibition affects cell death and survival.

Optical Biopsy, 1994

ABSTRACT

Scandinavian journal of gastroenterology, Jan 8, 2015

Photodynamic therapy (PDT) and radiofrequency ablation (RFA) are effective non-surgical options f... more Photodynamic therapy (PDT) and radiofrequency ablation (RFA) are effective non-surgical options for the treatment of Barrett's esophagus (BE) associated neoplasia. Development of subsquamous intestinal metaplasia after successful PDT and/or RFA is a recognized phenomenon; however, the occurrence of neoplasia arising from buried glands is a rare complication. This is a prospective case series of patients treated with PDT and/or RFA from 1999 to 2014 at University College London Hospital for neoplasia associated with BE, whose outcomes were analyzed retrospectively. Prior to any ablative therapy any visible nodularity was removed with endoscopic mucosal resection (EMR). After successful PDT and/or HALO RFA treatment, defined as a complete reversal of dysplasia and metaplasia, patients underwent endoscopic follow up using the Seattle protocol. A total of 288 patients were treated, 91 with PDT between 1999 and 2010, 173 with RFA between 2007 and 2014, and 24 with both PDT and RFA fo...

5th International Photodynamic Association Biennial Meeting, 1994

Five-aminolaevulinic acid (ALA) induced protoporphyrin IX (PpIX) has proven to be a useful photos... more Five-aminolaevulinic acid (ALA) induced protoporphyrin IX (PpIX) has proven to be a useful photosensitizer for photodynamic therapy (PDT). In living cells, the conversion of PpIX to photoinactive haem is catalyzed by ferrochelatase in the presence of tissue iron and inhibition of this final committed step results in increased accumulation of PpIX. The in vivo effect of a new iron chelator, 1,2-diethyl-3-hydroxypyridin-4-one (CP94), on the buildup of PpIX in different bladder layers was evaluated. In CP94 treated rats, 5 - 7 hours after intravesical instillation of ALA solution, the fluorescence intensity of PpIX in the urothelium was doubled whilst in the muscle layer it remained low at a similar level to those seen without the iron chelator. With CP94, further reduction of skin photosensitization is possible as a similar photodynamic effect on the bladder could be achieved at lower ALA concentration. The addition of CP94 seems an effective and convenient way to potentiate ALA induced PpIX tissue selectivity.

Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XX, 2011

The diagnosis and treatment of pancreaticobiliary malignancy is of major interest to our group. B... more The diagnosis and treatment of pancreaticobiliary malignancy is of major interest to our group. Building on prior work, we undertook a phase I study of verteporfin photodynamic therapy in patients with locally advanced, unresectable, pancreatic cancer. We also initiated an optical diagnostic study using elastic scattering spectroscopy (ESS) of the normal-appearing periampullary duodenal mucosa in vivo to investigate the hypothesis

Gut, 1997

A major drawback of laser endoscopy in the palliation of malignant dysphagia is the need for repe... more A major drawback of laser endoscopy in the palliation of malignant dysphagia is the need for repeated treatments. This study was designed to test whether external beam radiotherapy would reduce the necessity for repeated laser therapy. Sixty seven patients with inoperable oesophageal or gastric cardia cancers and satisfactory swallowing after initial laser recanalisation were randomised to palliative external beam radiotherapy (30 Gy in 10 fractions) or no radiotherapy. All patients underwent a 'check' endoscopy five weeks after initial recanalisation and were subsequently reendoscoped only for recurrent dysphagia, which occurred in 59 patients. Dysphagia was relieved equally well in both groups and the improvement was maintained with further endoscopic treatment. The initial dysphagia controlled interval and the duration between procedures required to maintain lifelong palliation (treatment interval) increased from five to nine weeks (median) in the radiotherapy group (p &l...

British journal of cancer, Jan 6, 2005

Photochemical internalisation (PCI) is a technique for releasing biologically active macromolecul... more Photochemical internalisation (PCI) is a technique for releasing biologically active macromolecules from endocytic vesicles by light activation of a photosensitiser localised in the same vesicles of targeted cells. This study investigated the PCI of the toxin gelonin as a way of enhancing the effect of photodynamic therapy (PDT) on a human malignant fibrous histiocytoma transplanted into nude mice using the photosensitiser disulphonated aluminium phthalocyanine (AlPcS(2a)). Pharmacokinetic studies after intraperitoneal administration showed that the serum level of AlPcS(2a) fitted a biexponential model (half-lives of 1.8 and 26.7 h). The tumour concentration was roughly constant up to 48 h, although fluorescence microscopy showed that the drug location was initially mainly vascular, but became intracellular by 48 h. To compare PDT with PCI, 48 h after intraperitoneal injection of 10 mg kg(-1) AlPcS(2a), and 6 h after direct intratumour injection of 50 microg gelonin (PCI) or a simil...

International journal of gastrointestinal cancer, 2005

The prognosis of patients with pancreatic and biliary tract cancer treated with conventional ther... more The prognosis of patients with pancreatic and biliary tract cancer treated with conventional therapies such as stent insertion or chemotherapy is often poor, and new approaches are urgently needed. Surgery is the only curative treatment but is appropriate in less than 20% of cases, and even then it is associated with a 5-yr survival of less than 30% in selected series. Photodynamic therapy represents a novel treatment for pancreaticobiliary malignancy. It is a way of producing localized tissue necrosis with light, most conveniently from a low-power, red laser, after prior administration of a photosensitizing agent, thereby initiating a non-thermal cytotoxic effect and tissue necrosis. This review outlines the mechanisms of action of photodynamic therapy including direct cell death, vascular injury, and immune system activation, and summarizes the results of preclinical and clinical studies of photodynamic therapy for pancreaticobiliary malignancy.

British journal of cancer, Jan 16, 2004

Photodynamic therapy (PDT) requires a photosensitising drug, light and oxygen. While it is known ... more 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...

Optical Fibers in Medicine IV, 1989

ABSTRACT A new ball-tip fibre optic device has been assessed for the purpose of laser angioplasty... more ABSTRACT A new ball-tip fibre optic device has been assessed for the purpose of laser angioplasty. A pulsed Neodymium-YAG laser producing 100 p.s pulses at a repetition rate of 10 Hz was used to ablate human cadaver arterial tissue using approximately 500 mJ per pulse at a wavelength of 1064 nm or 300 mJ at a wavelength of 1.3 μm. Both wavelengths are capable of ablating atheroma with little histological evidence of surrounding thermal damage. Crater depths of about 5 μm per Joule were produced using 1064 nm with normal tissue exposed under saline. Crater depth increases by about 50% when exposures are carried out under blood and when diseased arterial tissue is exposed the crater depth is almost doubled. Depth of ablation with a wavelength of 1.3 μm is 3 to 4 times greater than with 1064 nm for the same exposure and a similar increased response is seen for diseased tissue or in the presence of blood. Further experiments at 1064 nm have shown that the ball-tip device has advantages over bare fibre or sapphire tipped devices in the recanalisation of occluded femoral vessels in an artificial circulation.

Reviews in Gynaecological Practice, 2004

ABSTRACT The conventional surgical treatment for women with symptomatic uterine fibroids is a hys... more ABSTRACT The conventional surgical treatment for women with symptomatic uterine fibroids is a hysterectomy. Hysterectomy guarantees the removal of all uterine fibroids without a risk of recurrence. It also guarantees the cure of symptoms such as menorrhagia and pressure effects and has been shown to be associated with a high degree of patient satisfaction and improved quality of life scores. However, in addition to women who desire fertility, there are a growing number of women who have completed their family who do not wish to undergo a hysterectomy. Uterine conserving surgical methods include myomectomy or fibroid shrinkage either by embolisation/laparoscopic clipping of both uterine arteries or myolysis.This article reviews the surgical alternatives to hysterectomy and analyses the data that is currently available with each method. Laparoscopic interstitial laser photocoagulation of uterine fibroids is a relatively new modality of treatment and is carried out in our centre. Results of this method are presented and discussed in this article.Myomectomy is associated with significant morbidity and difficulty in long term management because of high recurrence rates. Surgical alternatives to myomectomy are still limited to large series in a few centres with a special interest in the procedure developed. Well designed long term studies are required to properly evaluate the efficacy and feasibility of each procedure in normal practice and its effect on infertility.

Proceedings of SPIE - The International Society for Optical Engineering

Comparison of holmium:YSGG versus Nd:YAG in an artificial circulation model. [Proceedings of SPIE... more Comparison of holmium:YSGG versus Nd:YAG in an artificial circulation model. [Proceedings of SPIE 1642, 120 (1992)]. Roy N. Lawrence, Jonathan A. Michaels, Stephen G. Bown. Abstract. The effects of pulsed Holmium:Yttrium ...

Gastroenterology

An unselected consecutive series of 826 patients admitted for acute upper gastrointestinal bleedi... more An unselected consecutive series of 826 patients admitted for acute upper gastrointestinal bleeding underwent urgent endoscopy. Peptic ulcers were found in 402 (49%). Of the 329 ulcer craters that could be fully examined, visible vessels were identified in 156 (47%), other stigmata of recent hemorrhage in 66, and no stigmata of recent hemorrhage in 107. One hundred twenty-nine patients with stigmata of recent hemorrhage (93 of whom had visible vessels) randomly allocated to no endoscopic treatment were observed for evidence of further bleeding. Fifty-four of the 93 patients (58%) with visible vessels rebled, compared with 2 of 36 (6%) with other stigmata of recent hemorrhage. No patient without stigmata of recent hemorrhage rebled. Twenty-seven patients in whom a visible vessel in a gastric ulcer was identified at endoscopy underwent urgent partial gastrectomy because of recurrent bleeding. The vessel identified at endoscopy was found in 26 of 27 resection specimens (96%). The arterial vessel wall protruded above the surface of the ulcer crater in 10 specimens, and clot in continuity with a breach in the vessel wall protruded in a further 10 specimens. Postoperative angiography, when technically possible, showed that the breached artery ran across the base of the ulcer in all of these specimens. Pathological changes were common in the bleeding artery and included arteritis in 24 of 29 (83%) eroded arteries found in these specimens, with aneurysmal dilatation in 14 of 27 (52%) bleeding points that could be fully examined. The ulcer had penetrated to serosa in 13 specimens (45%). The bleeding artery had a mean external diameter of 0.7 mm with a range of 0.1-1.8 mm. This study provides new information about the nature of the bleeding vessel in gastric ulcers, and some of this information is relevant in planning studies of endoscopic therapy for bleeding peptic ulcers. It validates the endoscopic identification of a visible vessel, and confirms that such identification has a high predictive value for the development of recurrent hemorrhage.

Gastroenterology

The drawbacks of monopolar electrocoagulation in the control of gastrointestinal bleeding include... more The drawbacks of monopolar electrocoagulation in the control of gastrointestinal bleeding include tissue adherence, unpredictable energy deposition, and a high incidence of tissue damage. Introduction of a conductive interfacial film of liquid between the monopolar electrode and the bleeding point during electrocoagulation may overcome these drawbacks. A prospective, controlled study was undertaken to evaluate the efficacy and safety of a monopolar electrode in liquid and dry modes when used to coagulate experimental canine bleeding ulcers. All experiments were done in open fashion via a gastrotomy with hand-held electrodes. An analog computer, which could be connected between a standard electrosurgical generator and the electrode, was designed and built to monitor and control the energy delivered to the tissue. Both liquid and dry electrodes were highly effective in stopping bleeding. The liquid electrode was found to be superior to the dry electrode in that tissue adherence was eliminated and energy deposition was more predictable, varying less with angle of incidence. The liquid electrode caused less macroscopic serosal damage and less full-thickness histologic damage if the total energy or number of pulses was limited; however, both caused microscopic full-thickness damage in one-half of the experimental ulcers treated, although no perforations occurred.

Photodiagnosis and Photodynamic Therapy, 2011

administration of 5-aminolevulinic acid (ALA). Porphyrin levels in urine were determined for norm... more administration of 5-aminolevulinic acid (ALA). Porphyrin levels in urine were determined for normal and tumor-bearing mice administered with ALA. Both uroporphyrin (UP) and coproporphyrin (CP) levels in urine at 3 h after ALA administration were significantly higher in tumor-bearing than in normal mice. Some porphyrin isomers differed in distribution between normal and tumor-bearing mice. Since no porphyrin level differences were observed without ALA administration, abnormal porphyrin metabolism in tumor cells could influence the porphyrin levels and isomer distributions. These data suggest that porphyrin-based cancer screening may be made possible with ALA administration.

Advances in experimental medicine and biology, 2003

Photodynamic therapy (PDT) is a treatment for various malignant and benign lesions using light-ac... more Photodynamic therapy (PDT) is a treatment for various malignant and benign lesions using light-activated photosensitising drugs in the presence of molecular oxygen. PDT causes tissue damage by a combination of processes involving the production of reactive oxygen ...

Photodiagnosis and Photodynamic Therapy, 2011

Poster Abstracts 187 species (ROS). Depending on the type of cells, photosensitizer and light dos... more Poster Abstracts 187 species (ROS). Depending on the type of cells, photosensitizer and light doses, PDT has been shown to induce cell apoptosis, necrosis and autophagy. PDT is also known to activate cell survival pathways. The final PDT outcome is dependent on the interplay between PDT-induced cell death and survival signals. One of the most important cell survival signals is mediated through phosphatidylinositol 3-kinase (PI3K) pathway. This study focused on understanding the effects of PDT on PI3K pathway and how the interaction between PDT and PI3K pathway inhibition affects cell death and survival.

Optical Biopsy, 1994

ABSTRACT

Scandinavian journal of gastroenterology, Jan 8, 2015

Photodynamic therapy (PDT) and radiofrequency ablation (RFA) are effective non-surgical options f... more Photodynamic therapy (PDT) and radiofrequency ablation (RFA) are effective non-surgical options for the treatment of Barrett's esophagus (BE) associated neoplasia. Development of subsquamous intestinal metaplasia after successful PDT and/or RFA is a recognized phenomenon; however, the occurrence of neoplasia arising from buried glands is a rare complication. This is a prospective case series of patients treated with PDT and/or RFA from 1999 to 2014 at University College London Hospital for neoplasia associated with BE, whose outcomes were analyzed retrospectively. Prior to any ablative therapy any visible nodularity was removed with endoscopic mucosal resection (EMR). After successful PDT and/or HALO RFA treatment, defined as a complete reversal of dysplasia and metaplasia, patients underwent endoscopic follow up using the Seattle protocol. A total of 288 patients were treated, 91 with PDT between 1999 and 2010, 173 with RFA between 2007 and 2014, and 24 with both PDT and RFA fo...

5th International Photodynamic Association Biennial Meeting, 1994

Five-aminolaevulinic acid (ALA) induced protoporphyrin IX (PpIX) has proven to be a useful photos... more Five-aminolaevulinic acid (ALA) induced protoporphyrin IX (PpIX) has proven to be a useful photosensitizer for photodynamic therapy (PDT). In living cells, the conversion of PpIX to photoinactive haem is catalyzed by ferrochelatase in the presence of tissue iron and inhibition of this final committed step results in increased accumulation of PpIX. The in vivo effect of a new iron chelator, 1,2-diethyl-3-hydroxypyridin-4-one (CP94), on the buildup of PpIX in different bladder layers was evaluated. In CP94 treated rats, 5 - 7 hours after intravesical instillation of ALA solution, the fluorescence intensity of PpIX in the urothelium was doubled whilst in the muscle layer it remained low at a similar level to those seen without the iron chelator. With CP94, further reduction of skin photosensitization is possible as a similar photodynamic effect on the bladder could be achieved at lower ALA concentration. The addition of CP94 seems an effective and convenient way to potentiate ALA induced PpIX tissue selectivity.

Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XX, 2011

The diagnosis and treatment of pancreaticobiliary malignancy is of major interest to our group. B... more The diagnosis and treatment of pancreaticobiliary malignancy is of major interest to our group. Building on prior work, we undertook a phase I study of verteporfin photodynamic therapy in patients with locally advanced, unresectable, pancreatic cancer. We also initiated an optical diagnostic study using elastic scattering spectroscopy (ESS) of the normal-appearing periampullary duodenal mucosa in vivo to investigate the hypothesis

Gut, 1997

A major drawback of laser endoscopy in the palliation of malignant dysphagia is the need for repe... more A major drawback of laser endoscopy in the palliation of malignant dysphagia is the need for repeated treatments. This study was designed to test whether external beam radiotherapy would reduce the necessity for repeated laser therapy. Sixty seven patients with inoperable oesophageal or gastric cardia cancers and satisfactory swallowing after initial laser recanalisation were randomised to palliative external beam radiotherapy (30 Gy in 10 fractions) or no radiotherapy. All patients underwent a 'check' endoscopy five weeks after initial recanalisation and were subsequently reendoscoped only for recurrent dysphagia, which occurred in 59 patients. Dysphagia was relieved equally well in both groups and the improvement was maintained with further endoscopic treatment. The initial dysphagia controlled interval and the duration between procedures required to maintain lifelong palliation (treatment interval) increased from five to nine weeks (median) in the radiotherapy group (p &l...

British journal of cancer, Jan 6, 2005

Photochemical internalisation (PCI) is a technique for releasing biologically active macromolecul... more Photochemical internalisation (PCI) is a technique for releasing biologically active macromolecules from endocytic vesicles by light activation of a photosensitiser localised in the same vesicles of targeted cells. This study investigated the PCI of the toxin gelonin as a way of enhancing the effect of photodynamic therapy (PDT) on a human malignant fibrous histiocytoma transplanted into nude mice using the photosensitiser disulphonated aluminium phthalocyanine (AlPcS(2a)). Pharmacokinetic studies after intraperitoneal administration showed that the serum level of AlPcS(2a) fitted a biexponential model (half-lives of 1.8 and 26.7 h). The tumour concentration was roughly constant up to 48 h, although fluorescence microscopy showed that the drug location was initially mainly vascular, but became intracellular by 48 h. To compare PDT with PCI, 48 h after intraperitoneal injection of 10 mg kg(-1) AlPcS(2a), and 6 h after direct intratumour injection of 50 microg gelonin (PCI) or a simil...

International journal of gastrointestinal cancer, 2005

The prognosis of patients with pancreatic and biliary tract cancer treated with conventional ther... more The prognosis of patients with pancreatic and biliary tract cancer treated with conventional therapies such as stent insertion or chemotherapy is often poor, and new approaches are urgently needed. Surgery is the only curative treatment but is appropriate in less than 20% of cases, and even then it is associated with a 5-yr survival of less than 30% in selected series. Photodynamic therapy represents a novel treatment for pancreaticobiliary malignancy. It is a way of producing localized tissue necrosis with light, most conveniently from a low-power, red laser, after prior administration of a photosensitizing agent, thereby initiating a non-thermal cytotoxic effect and tissue necrosis. This review outlines the mechanisms of action of photodynamic therapy including direct cell death, vascular injury, and immune system activation, and summarizes the results of preclinical and clinical studies of photodynamic therapy for pancreaticobiliary malignancy.

British journal of cancer, Jan 16, 2004

Photodynamic therapy (PDT) requires a photosensitising drug, light and oxygen. While it is known ... more 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...

Optical Fibers in Medicine IV, 1989

ABSTRACT A new ball-tip fibre optic device has been assessed for the purpose of laser angioplasty... more ABSTRACT A new ball-tip fibre optic device has been assessed for the purpose of laser angioplasty. A pulsed Neodymium-YAG laser producing 100 p.s pulses at a repetition rate of 10 Hz was used to ablate human cadaver arterial tissue using approximately 500 mJ per pulse at a wavelength of 1064 nm or 300 mJ at a wavelength of 1.3 μm. Both wavelengths are capable of ablating atheroma with little histological evidence of surrounding thermal damage. Crater depths of about 5 μm per Joule were produced using 1064 nm with normal tissue exposed under saline. Crater depth increases by about 50% when exposures are carried out under blood and when diseased arterial tissue is exposed the crater depth is almost doubled. Depth of ablation with a wavelength of 1.3 μm is 3 to 4 times greater than with 1064 nm for the same exposure and a similar increased response is seen for diseased tissue or in the presence of blood. Further experiments at 1064 nm have shown that the ball-tip device has advantages over bare fibre or sapphire tipped devices in the recanalisation of occluded femoral vessels in an artificial circulation.