Biomedical subjects

Georges Wagnières

Publications and source records attributed to Georges Wagnières.

10 recordsLinked to original sources

PubMed2006

Preclinical comparison of mTHPC and verteporfin for intracavitary photodynamic therapy of malignant pleural mesothelioma.

Efficacy and tumour selectivity of photodynamic therapy with two clinically approved sensitizers (mTHPC, verteporfin) were assessed for focal intracavitary photodynamic therapy (PDT) in rodents with malignant pleural mesothelioma (MPM) at recommended drug-light conditions and at escalating sensitizer dosages. MPM tumours were generated in 15 Fischer rats by subpleural mediastinal tumour cell injection followed after 5 days by intracavitary PDT with light delivery monitored by in situ dosimetry. Animals were intravenously sensitized either with mTHPC (0.1 mg/kg, n = 3; 0.2 mg/kg, n = 3) followed after 4 days by illumination with 20 J/cm(2) at 652 nm, or with verteporfin (0.6 mg/kg, n = 3; 1.2 mg/kg, n = 3) followed after 20 min by illumination with 100 J/cm(2) at 689 nm. Three untreated tumour-bearing animals served as controls. Histological evaluation of the treated tumour and of adjacent normal organs was performed 10 days after tumour implantation. The extent of PDT-induced tumour necrosis was compared to the non-necrosed area and expressed in percentage. A locally invasive growing MPM tumour (3.1 +/- 1 mm diameter) without spontaneous necrosis diameter was found in all animals. For both sensitizers, focal intracavitary PDT was well tolerated at drug-light conditions recommended for clinical applications. Mediastinal organs were spared for both sensitizers but verteporfin resulted in a higher extent of tumour necrosis (80%) than mTHPC (50%). Drug dose escalation revealed a higher extent of PDT-related tumour necrosis for both sensitizers (mTHPC 55%, verteporfin 88%), however, verteporfin-PDT was associated with a higher toxicity than mTHPC-PDT.

Animals↗

PubMed2005

Influence of the menstrual cycle on aminolevulinic acid induced protoporphyrin IX fluorescence in the endometrium: in vivo study.

BACKGROUND AND OBJECTIVES: In vitro studies indicated that compared to postmenopausal women, premenopausal women had increased aminolevulinic acid induced protoporphyrin IX (ALA-induced PpIX) fluorescence expression in the endometrium. The aim of this study was to evaluate menstrual cycle dependency of ALA-induced PpIX fluorescence in the endometrium in vivo. STUDY DESIGN/PATIENTS AND METHODS: Thirteen patients were included for in vivo spectrofluorometric measurements of ALA-induced PpIX in the endometrium and 51 patients for fluorescence hysteroscopy. Two milliliter of a 2% 5-ALA-solution at pH = 4.0 (ASAT AG/Zug, Switzerland) was topically administrated just before spectrofluorometry and 4 hours before hysteroscopy. Spectrofluorometry: Optical fiber based. Fluorescence hysteroscopy: STORZ-D-Light system (Storz, Tuttlingen, Germany). Histological classification of curettage and bioptic endometrial tissue stained with hematoxylin and eosin (H&E). RESULTS: Hysteroscopic and in vivo spectrofluorometric measurements showed an increase of ALA-induced PpIX fluorescence in the secretory and hyperplastic endometrium compared to proliferative and atrophic endometrium. CONCLUSIONS: The accuracy of fluorescence hysteroscopy and the success of the photodynamic endometrial ablation using ALA-induced PpIX may depend on the hormonal influence of the menstrual cycle. The mechanisms responsible for the increased ALA-induced PpIX fluorescence in the secretory versus proliferative phase of the menstrual cycle deserve further studies.

Adult↗

PubMed2004

Photodynamic endometrial ablation for the treatment of dysfunctional uterine bleeding: a preliminary report.

BACKGROUND AND OBJECTIVES: To evaluate feasibility and functional effects of photodynamic endometrial ablation (PEA) in patients. STUDY DESIGN/PATIENTS AND METHODS: A total of 15 PEAs has been performed in 11 patients using topically applied 5-aminolevulinic acid (ALA) solutions and a balloon-light diffuser (160 J/cm(2), 635 nm). Uterine bleeding intensity has been determined on a daily basis 3 months prior to and up to 6 months after endometrial ablation using an analogous scale scoring from 1 (spotting) to 6 U (severe bleeding). Statistical analysis by unpaired Student's t-test. RESULTS: The mean number of bleeding units per cycle (n = 44) was 35.7 prior to PEA. The decrease in bleeding units was significant for the months 1-3 (24.4 U per cycle; P = 0.03), but not for the months 4-6 (25.9 U; P = 0.11) following PEA. CONCLUSIONS: PEA is feasible and provides a significant short-term reduction of uterine bleeding.

Adult↗

PubMed2004

Time-dependent hexaminolaevulinate induced protoporphyrin IX distribution after topical application in patients with cervical intraepithelial neoplasia: A fluorescence microscopy study.

BACKGROUND AND OBJECTIVES: Compared to the conventional management of cervical intraepithelial neoplasia (CIN) the potential advantage of photodynamic therapy (PDT) for the treatment of cervical human papilloma virus (HPV)-related disease encompasses a minimal invasive procedure with reduced risk of profuse bleeding as a consequence of conization, and possibly more favorable long-term results avoiding cervical stenosis. At present little is known about the precise time-dependent distribution and histological localization of hexaminolaevulinate (HAL) induced protoporphyrin IX (PPIX) fluorescence in healthy tissue and in CIN. The aim of this study was to use ex vivo fluorescence microscopy to determine whether PPIX is selectively induced by neoplastic cells of the cervical epithelium at various times after topical application. STUDY DESIGN/MATERIALS AND METHODS: Cold cream containing 0.5% HAL was applied by means of cervical cap over various periods of time. We analyzed 52 healthy cervical mucosa and 84 CINs. RESULTS: At time delay 100 (+/-10) minutes, high epithelial fluorescence and a significant selectivity between epithelium and underlying lamina propria was found. By contrast, no significant difference between healthy and neoplastic tissues, or between low and high-grade epithelial dysplasia (P > or = 0.05), was observed at any time point. CONCLUSIONS: Application of HAL 0.5% cream to the cervix induced selective fluorescence in epithelial cells. The optimal ratio with a homogeneous PPIX distribution was obtained after 100 ( +/- 10) minutes cream application, which should be evaluated further for PDT.

Administration, Topical↗

PubMed2003

Photodynamic endometrial ablation: morphological study.

BACKGROUND AND OBJECTIVES: Endometriumablation provides an alternative treatment modality to hysterectomy for dysfunctional uterine bleeding (DUB). Its feasibility was demonstrated in animal studies. The purpose of this study was the evaluation of histological changes following photodynamic endometrial ablation in patients. STUDY DESIGN/MATERIALS AND METHODS: 5-Aminolevulinic acid (ALA) was topically applied in three premenopausal and one postmenopausal patient 4-6 hours before laser-illumination. ALA-concentration: 100-400 g/ml, NaOH-titration (pH 5.5). Volume applied, 1.5-2.0 ml; intrauterine balloon-lightdiffuser; wavelength, 635 nm; lightdose, 160 J/cm(2). Hysterectomy was performed 3-152 days after photodynamic ablation. Histological examination was carried out on endometrium sections stained with hematoxylin and eosin (H&E). RESULTS: Necrosis including the full thickness of the endometrium was found 3 days after photodynamic endometrial ablation. Specimens collected after 35 and 152 days did not exhibit fibrosis or adhesions. Foci of preserved endometrium were detected in all patients. CONCLUSIONS: Photodynamic endometrial ablation is selective and does not cause endometrial fibrosis or adhesions.

Adult↗

PubMed2003

In vivo autofluorescence imaging of early cancers in the human tracheobronchial tree with a spectrally optimized system.

The changes in the autofluorescence characteristics of the bronchial tissue is of crucial interest as a cancer diagnostic tool. Evidence exists that this native fluorescence or autofluorescence of bronchial tissues changes when they turn dysplastic and to carcinoma in situ. There is good agreement that the lesions display a decrease of autofluorescence in the green region of the spectrum under illumination with violet-light, and a relative increase in the red region of the spectrum is often reported. Imaging devices rely on this principle to detect early cancerous lesions in the bronchi. Based on a spectroscopic study, an industrial imaging prototype is developed to detect early cancerous lesions in collaboration with the firm Richard Wolf Endoskope GmbH, Germany. A preliminary clinical trial involving 20 patients with this spectrally optimized system shows that the autofluorescence can help to detect most lesions that would otherwise have remained invisible to an experienced endoscopist under white light illumination. A systematic off line analysis of the autofluorescence images pointed out that real-time decisional functions can be defined to reduce the number of false positive results. Using this method, a positive predictive value (PPV) of 75% is reached using autofluorescence only. Moreover, a PPV of 100% is obtained, when combining the white light (WL) mode and the autofluorescence (AF) mode, at the applied conditions. Furthermore, the sensitivity is estimated to be twice higher in the AF mode than in WL mode.

Aged↗

PubMed2003

Evaluation of the photosensitizer Tookad for photodynamic therapy on the Syrian golden hamster cheek pouch model: light dose, drug dose and drug-light interval effects.

We have evaluated the efficacy of the new photosensitizer (PS) Tookad in photodynamic therapy (PDT) in vivo. This PS is a palladium-bacteriopheophorbide presenting absorption peaks at 762 and 538 nm. The light dose, drug dose and drug injection-light irradiation interval (DLI), ranging between 100 and 300 J/cm2, 1 and 5 mg/kg and from 10 to 240 min, respectively, were varied, and the response to PDT was analyzed by staging the macroscopic response and by the histological examination of the sections of the irradiated cheek pouch. The level of PDT response, macroscopically and histologically, shows a strong dependence on the DLI, light dose and drug dose at the applied conditions in the normal hamster cheek pouch. A decay of the tissular response with increasing DLI is observed corresponding to a time of half-maximum response ranging from 10 to 120 min, depending on drug dose and light dose. The tissues affected at the lowest doses are predominantly the vascularized diffuse connective tissue situated between the inner and outer striated muscle (SM) layers as well as these muscle layers themselves. The highest response at the shortest DLI and the absence of a measurable response at DLI longer than 240 min at 300 J/cm2 and drug dose of 5 mg/kg are characteristics of a predominantly vascular effect of this PS. This observation suggests that Tookad could be effective in PDT of vascularized lesions or pathologies associated with the proliferation of neovessels.

Animals↗

PubMed2002

Photoeradication of Helicobacter pylori using 5-aminolevulinic acid: preliminary human studies.

BACKGROUND AND OBJECTIVES: Helicobacter pylori (HP) is an endemic pathogenic bacterium causing gastritis and gastroduodenal ulceration in humans and is linked to the development of gastric malignancies. These first human in vivo studies investigated the photoeradication of HP using laser and white light. STUDY DESIGN/MATERIALS AND METHODS: In 13 HP-positive volunteers, a zone of gastric antrum was irradiated with laser (410 nm, 50 J/cm(2)) or endoscopic white light (10 J/cm(2)) 45 minutes after oral 5-aminolevulinic acid (5-ALA) 20 mg/kg. HP-eradication was assessed by biopsy urease test and HP-culture from irradiated and control zones 5 minutes, 4 and 48 hours post-irradiation. RESULTS: A maximum eradication effect was achieved at 4 hours post-irradiation when 85% of biopsies in the monochromatic and 66% in the white light exposed zones, and 58 and 33% in the respective control zones were HP-negative. CONCLUSIONS: HP numbers were greatly reduced following exposure to 5-ALA and either laser or white light in vivo. Photoeradication appears feasible, but further light dosimetry and the development of convenient application methods is required.

Adult↗

PubMedDate not supplied

On the role of iron and one of its chelating agents in the production of protoporphyrin IX generated by 5-aminolevulinic acid and its hexyl ester derivative tested on an epidermal equivalent of human skin.

Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) or its derivatives as precursors of protoporphyrin IX (PPIX) is routinely used in dermatology for the treatment of various pathologies. However, this methodology suffers to some extent from a limited efficacy. Therefore, the main goal of this study was to investigate the modulation and pharmacokinetics of PPIX buildup after a 5 h incubation with ALA (1.5 mM) and one of its derivatives, the hexyl ester of ALA (h-ALA) (1.5 mM), on the human epidermal equivalent Epidex. PPIX production was modulated with (L+) ascorbic acid iron (II) salt (LAI) or the iron (II)-specific chelating agent deferoxamine (DFO). PPIX fluorescence from the Epidex layers was measured up to 150 h after the precursor administration using a microspectrofluorometer (lambda(ex): 400 +/- 20 nm; lambda(det): 635 nm). The maximum PPIX fluorescence intensity induced by h-ALA was about 1.7 x larger than that induced by ALA. The addition of DFO resulted in a more than 50% increase in PPIX fluorescence for both precursors. The decay half life measured for PPIX fluorescence is 30 and 42.5 h, respectively, for ALA and h-ALA. These half lives are doubled when the samples contain DFO. In the samples with the highest fluorescence intensity, a modified fluorescence spectrum was observed after 10 h, with the emergence of a peak at 590 nm, which is attributed to zinc protoporphyrin IX (Zn PPIX).

Aminolevulinic Acid↗

PubMedDate not supplied

Blue-violet excited autofluorescence spectroscopy and imaging of normal and cancerous human bronchial tissue after formalin fixation.

Autofluorescence (AF) imaging is a powerful tool for the detection of (pre-)neoplastic lesions in the bronchi. Several endoscopic imaging systems exploit the spectral and intensity contrast of AF between healthy and (pre-)neoplastic bronchial tissues, yet, the mechanisms underlying these contrasts are poorly understood. In this report, the effect of formalin fixation on the human bronchi AF, hence on the contrast, was studied by spectrofluorometric point measurements and DAFE (Diagnostic AutoFluorescence Endoscopy) broad field imaging. Generally, formalin-fixed samples have higher AF intensity than in vivo, whereas the emission spectral shape is similar. Additionally, the spectrofluorometric data showed a moderate decrease of the AF intensity on (pre-)neoplastic lesions relative to the healthy bronchial samples. However, this decrease was lower than that reported from in vivo measurements. Neither spectral measurements nor imaging revealed spectral contrast between healthy bronchial tissue and (pre-)neoplastic lesions in formalin. These results indicate that epithelial thickening and blood supply in the adjacent lamina propria are likely to play a key role in the generation of the AF contrast in bronchial tissues. Our results show that the AF contrast in bronchial tissues was significantly affected by standard, 10% buffered, formalin fixation. Therefore, these samples are not suited to AF contrast studies.

Bronchi↗