An image guided treatment platform for prostate cancer photodynamic therapy.

This study describes a multimodality images based platform to drive photodynamic therapies of prostate cancer using WST 11 TOOKAD Soluble drug. The platform integrates a pre-treatment planning tool based on magnetic resonance imaging and a per-treatment guidance tool based on transrectal ultrasound images. Evaluation of the platform on clinical data showed that prediction of the therapy outcome was possible with an accuracy of 90 %.

Efficiency of 5-ALA mediated photodynamic therapy on hypoxic prostate cancer: a preclinical study on the Dunning R3327-AT2 rat tumor model.

OBJECTIVES: To evaluate photodynamic therapy (PDT) using 5-ALA-induced protoporphyrin IX (PPIX) in an in vivo hypoxic tumor model and its monitoring using MRI. MATERIAL AND METHODS: Dunning R3327-AT2 tumors were grafted in the neck of Copenhagen rats. PDT using 150 mg 5-ALA/kg i.v. was performed by focal interstitial illumination of the photosensitized tumor (λ=633 nm; fluence=100 J/cm(2)). MRI at baseline and 2 days after treatment (T1, T2 and dynamic gadolinium enhanced sequences) were performed. Necrosis volumes were determined on post-procedure MRI. Tumors were resected 2 days post-PDT and obtained necrosis was determined histopathologically. Intra-tumoral PPIX distribution was evaluated using confocal microscopy and tissue porphyrin quantification. RESULTS: Twenty rats were treated divided into three groups: continuous (n=7), fractionated illumination (n=7), and a control group receiving only light or only ALA or neither (n=6). Baseline MRI confirmed the hypoxic character of tumors. Necrosis volumes determined on posttreatment MRI were not reproducible and presented with important geometric and volumetric variability. Average necrosis volumes of 0.39 cc (0-0.874 cc) in the continuous group, 0.24 cc (0.107-0.436 cc) in the fractionated group and 0.012 cc (0-0.071 cc) in the control group were observed. Intra-tumoral PPIX distribution was heterogeneous and PPIX quantification revealed low intra-tumoral concentration. CONCLUSION: Necrosis volumes induced by 5-ALA-mediated PDT were highly variable and non reproducible, probably because of lack of intra-tissular oxygen. Photosensitizer was poorly represented inside the tumor and its distribution was heterogeneous. Our study suggests that 5-ALA-mediated PDT might not be the best management option for hypoxic prostatic adenocarcinoma.

An anatomically realistic and adaptable prostate phantom for laser thermotherapy treatment planning.

PURPOSE: To construct a phantom for prostate cancer laser based thermotherapy treatment planning and simulation. METHODS: A realistic and adaptable prostate phantom was designed. It exhibits the following properties: valid and complete description of the prostate anatomy, material with similar optical properties of prostate tissues and compatibility with clinical imaging protocols mainly multiparametric magnetic resonance (MR) and transrectal ultrasound imaging (TRUS). RESULTS: Preliminary experiments with the phantom using an interstitial laser treatment protocol allowed obtaining results similar to those obtained on preclinical model. CONCLUSIONS: These results proved that this phantom could allow a real simulation of laser therapy procedure: target definition and fibers' placement optimization using MR imaging, treatment delivery, and finally treatment monitoring using TRUS imaging.

Terapia fotodinámica (PDT) en piel y estética: procedimiento, materiales y método en base a nuestra experiencia / Photodinamic therapy in skin and aesthetics: procedure, matherials and method based on our experience

La terapia fotodinámica (PTD) es un procedimiento cada vez más utilizado para tratar diversas afecciones dermatológicas y dermatoestéticas. Su aplicación obtiene buenos resultados en casos de carcinoma basocelular, enfermedad de Bowen, queratosis actínica, acné, rosácea y fotoenvejecimiento cutáneo. Los fotosensibilizantes y las fuentes de luz que se pueden utilizar son cada vez más variados, pero aún existe poco consenso en su metodología de aplicación, sistemas de irradiación y dosificaciones. En este artículo describimos los materiales y métodos disponibles en la actualidad y discutimos algunos detalles que, en base a nuestra experiencia, permiten mejorar los resultados. Presentamos también 5 casos clínicos ilustrativos de diferentes patologías (AU)

Photo Dynamic Therapy (PTD) is an increasingly used technique in Dermatology and Dermocosmetics. PDT has a wide range of medical applications for the treatment of extended cutaneous cancer, offering also very good results in the treatment of basal cell carcinoma, Bowen's disease, actinic keratosis, acne, rosacea and in cutaneous rejuvenation. The sensitizers and light sources used for photoactivation are also more and more varied but there is still no consensus regarding methods and energy dosage. This study describes material and methods which are currently available and discusses a few details, that based on our own experience, can improve results. Five illustrative cases of different conditions are presented (AU)

How best to halt and/or revert UV-induced skin ageing: strategies, facts and fiction.

Once considered mainly a cosmetic issue, photoageing research has long moved to the forefront of investigative dermatology. Besides obvious market pressures, increasing insight into the mechanistic overlap between UV-induced skin cancer and UV-induced skin ageing has contributed to this development. Also, as strategies that work to antagonize intrinsic skin ageing/senescence may also be exploited against photoageing (and vice versa!), it has become an important skin research challenge to dissect both the differences and the overlap mechanisms between these interwined, yet distinct phenomena. Finally, the current surge in putative 'antiageing' products, devices, and strategies - too many of which boldly promise to fight and/or repair the perils that come along with a lifetime spent in the sun in the absence of convincing evidence of efficacy - makes it particularly pertinent to critically review the available evidence to support often made antiageing claims. The current CONTROVERSIES feature, therefore, aimed to provide both guidance through, and critical voices in, the antiageing circus. Here, a panel of experts defines relevant key problems, points the uninaugurated to intriguing aspects of photoageing that one may not have considered before, highlights promising strategies for how best to halt and/or revert it, and spiritedly debates some controversially discussed approaches.

[Transpupillary thermotherapy and age-related macular degeneration]. / Thermothérapie transpupillaire et dégénérescence maculaire liée à l'âge.

Transpupillary thermotherapy (TTT) has been proposed over the last a few years for the treatment of subfoveal occult choroidal neovessels resulting from age-related degeneration (AMD) when they are symptomatic and associated with exudation. Several pilot studies have shown how this technique can decrease or slow down the progression of exudation related to choroidal neovessels. Based on these pilot studies, a randomized study (TTT4CNV) is in progress to evaluate the efficacy of TTT. While the inclusion of the patients in this study has come to an end, the therapeutic context of AMD has recently been changed with a permit to market Visudyn for photodynamic therapy (PDT) for some types of subfoveal occult choroidal neovessels. Moreover, the clinical studies in progress on photodynamic therapy and antiangiogenic drugs now make it possible to consider combined treatments possibly including TTT. This paper aims to provide a report on the current place and potential of TTT within the therapeutics available or soon available for subfoveal occult choroidal neovessels of AMD.

Treatment of leg telangiectases with a 532 nm KTP laser in multipulse mode.

BACKGROUND: The multiple mode emission emphasizes the efficacy of the KTP laser. OBJECTIVE: To evaluate the efficacy of a 532 nm KTP laser emitting in multipulse mode for the treatment of superficial 0.5-1 mm leg telangiectases. METHODS: A 532 nm KTP laser was used in a nonuniform pulse sequence or multipulse mode emission (three stacked pulses of 100 msec, 30 msec, 30 msec, and a delay between pulses of 250 msec), a fluence of 60 J/cm2, and a 0.75 mm collimated spot. No cooling was used. Fourteen female patients (average age 46 years, range 27-57 years), phototypes I-IV were examined with Doppler ultrasound to ensure their big veins were competent. A topography of the telangiectatic network was reported on a tracing plastic frame before each session and 6 weeks after the last one. These frames were digitized and the number of vessels (before and 6 weeks after each session) was determined using imaging software. Side effects, pain, and patient satisfaction were noted. RESULTS: Moderate pain, immediate erythema and edema, sometimes light scabbing, temporary hypopigmentation rarely, and no matting were observed. After one treatment, vessel clearing was 53% (P <.001). It increased to 78% (P <.001) 6 weeks after two treatments, to 85% (P <.05) 6 weeks after three treatments, and to 93% (NS) 6 weeks after four treatments. CONCLUSION: This nonuniform pulse sequence or multipulse mode emission emphasizes the efficacy of the KTP laser in this study. It provides a safe and effective treatment that achieved an important reduction of red leg veins telangiectases from 0.5 to 1 mm in diameter, with very few side effects.

Heat shock protein hyperexpression on chorioretinal layers after transpupillary thermotherapy.

PURPOSE: To assess a biological effect induced by temperature elevation during transpupillary thermotherapy (TTT). METHODS: Six pigmented rabbits were anesthetized, and TTT was performed on the right eye using an 810-nm diode laser installed on a slit lamp (spot size, 1.3 mm; duration, 60 seconds; power, 92-150 mW). A series of laser pulses were aimed at the posterior pole of the retina. The left eyes were used as the control. Twenty-four hours after laser irradiation, a histologic study was performed on the chorioretinal layers. Tissue samples were fixed in formalin and embedded in paraffin. A monoclonal antibody was used to detect heat shock protein (Hsp)70 immunoreactivity, followed by a biotinylated goat anti-mouse antibody, revealed by the avidin-biotin complex and the 3-amino-9-ethyl-carbazole (AEC) chromogen. Retinal structures were further identified by hematoxylin erythrosin saffron (HES) coloration. RESULTS: The photocoagulation threshold was found to be at the 150-mW laser power. Under this threshold, Hsp70 immunostaining was the strongest at the 127-mW power, with staining of some choroidal cells, including capillary endothelial cells. No Hsp70 immunoreactivity was observed on the retina. At the 107-mW power, Hsp70 reactivity was observed only in occasional choroidal cells. At the 98-mW power, only mild, diffuse Hsp70 immunoreactivity was observed in the choroid. At the 92-mW power, as in nonirradiated eyes, no Hsp70 immunoreactivity was detected. CONCLUSIONS: Subthreshold transpupillary 810-nm laser irradiation induces choroidal Hsp hyperexpression. This confirms that choroidal Hsp hyperexpression can be induced during TTT, as has been recently hypothesized by several investigators.

[Choroidal heat shock overexpression in transpupillary thermotherapy: preliminary results]. / Hyperexpression choroïdienne de Heat Shock Proteins au cours de la thermothérapie transpupillaire: résultats préliminaires.

PURPOSE: To assess retinochoroidal overexpression of heat shock proteins (HSP-70) induced by a transpupillary laser irradiation below the photocoagulation threshold. METHODS: Four pigmented rabbits were anesthetized and TTT was performed on the right eye using a 810nm diode laser (Iridis, Quantel-Medical, France) adapted on slit lamp (spot size: 1.3 mm, duration: 60 seconds; power 92-150 mW). Series of laser impacts were aimed at the posterior pole of the retina. Left eyes were used as control. Twenty-four hours after laser irradiation, a histological study was done on chorioretinal layers. Tissue samples were fixed in formalin and embedded in paraffin. A monoclonal antibody was used to detect HSP-70 immunoreactivity (mouse IgGl, SPA-810, Stress Gen, Canada), followed by a biotinylated goat antimouse antibody (Dako, Denmark), revealed by the avidin-biotin complex (Vectastain kit, Vector, USA) and the AEC chromogen. Retinal structures were further identified by HES coloration. RESULTS: The photocoagulation threshold was obtained for laser power at 150 mW. Under this threshold, HSP-70 immunostaining was the strongest for power 127 mW with a staining of some choroidal cells, including capillary endothelial cells. No HSP-70 immunoreactivity was observed on the retina. For the laser power 107 mW, HSP-70 reactivity was observed only in occasional choroidal cells. For the laser power 92 mW, as for nonirradiated eyes, no HSP-70 immunoreactivity was detected. CONCLUSIONS: Transpupillary 810 nm laser irradiation under the photocoagulation threshold induces choroidal HSP overexpression. This study concludes that choroidal HSP overexpression can be induced during TTT.

Inhaled nitric oxide modulates leukocyte kinetics in the mesenteric venules of endotoxemic rats.

OBJECTIVE: to determine whether inhaled nitric oxide (NO) would alter leukocyte kinetics in the septic microvasculature. DESIGN: Randomized, controlled trial. SETTING: Experimental laboratory. SUBJECTS: Male Sprague Dawley rats. INTERVENTIONS: Rats were treated with either saline or endotoxin (10 mg/kg, iv) and then allowed to breathe either air or air plus NO (10 ppm). MEASUREMENTS AND MAIN RESULTS: After a 4-hr period, rolling, firm adhesion, and emigration of leukocytes and endothelial dysfunction were monitored in mesenteric venules by using intravital videomicroscopy. Compared with controls, endotoxemic rats exhibited a profound influx in mesenteric venule rolling leukocytes (55+/-17 vs. 70+/-19 leukocytes/min; p < .05), associated with a reduction of leukocyte rolling velocity (83+/-14 vs. 34+/-3 microm/sec; p < .05). In endotoxemic rats, venular endothelium leukocyte firm adhesion (1.15+/-0.32 vs. 4.08+/-0.96 leukocytes/ 100 microm; p < .05) and emigration (0.84+/-0.47 vs. 4.23+/-1.2 leukocytes/100 microm; p < .05) increased compared with controls. Inhaled NO had no effect on leukocyte kinetics in control rats. Inhaled NO significantly attenuated endotoxin-induced venular endothelium leukocyte adhesion (4.08+/-0.96 vs. 1.86+/-0.76 leukocytes/100 microm; p < .05) and emigration (4.23+/-1.2 vs. 1.68+/-0.72 leukocytes/100 microm; p < .05). Compared with control rats, macromolecular (FITC-dextran) vascular leakage, expressed as the perivenular/intravenular fluorescence intensity ratio, increased in endotoxemic rats (0.56+/-0.02 vs. 0.81+/-0.05; p < .01). Endotoxin-induced macromolecular vascular leakage increases were partially prevented by inhaled NO (0.66+/-0.01 vs. 0.56+/-0.02; p < .05). CONCLUSION: These observations suggest that inhaled NO reduces leukocyte adhesion and the degree of vascular permeability dysfunction in mesenteric venule of endotoxemic rats.