Naiyan Huang

Analyse clinique de 1 949 angiomes plans traités par thérapie photodynamique vasculaire (Gu's PDT)

Resume Introduction Les techniques lasers utilisees actuellement ne permettent que tres difficilement d’obtenir un blanchiment complet des angiomes plans. Le recours a la therapie photodynamique vasculaire (GUs PDT) pourrait offrir une alternative therapeutique efficace. Malades et methode Mille trois cent quatre-vingt-cinq malades atteints de 1 949 angiomes plans ont ete traites par cette technique. Le traitement etait realise apres injection intraveineuse d’Hematoporphyrine derivee (HpD) ou bien d’Hematoporphyrin Monomethyl Ether (HMME) a une dose de 3-7 mg/kg. Immediatement apres injection, la lesion vasculaire etait irradiee avec un spot de 2 a 8 cm. Plusieurs longueurs d’ondes ont ete utilisees, typiquement de 488 a 578 nm avec des irradiances de 50 a 100 mW/cm 2 . Les fluences appliquees ont ainsi varie de 90 a 540 J/cm 2 . Resultats Ce traitement s’est montre efficace sur 99,7 p. 100 des 1 949 lesions traitees apres une seule seance. Le blanchiment etait cependant variable : pour 128 lesions (6,6 p. 100), un blanchiment total a pu etre obtenu. Pour 746 lesions (38,3 p. 100), le resultat etait bon (blanchiment > 75 p. 100), modere pour 923 lesions (47,4 p. 100) et faible pour 145 lesions (7,4 p. 100). Enfin, pour sept lesions (0,3 p. 100) aucune amelioration n’a pu etre notee. L’analyse clinique des resultats montre que les angiomes plans de couleur rose repondent beaucoup mieux a la therapie photodynamique vasculaire (GUs PDT) que les angiomes violets. Conclusion Cette nouvelle technique est efficace, detruit selectivement les lesions vasculaires et n’a pratiquement aucun risque cicatriciel.

Twenty Years of Clinical Experience with a New Modality of Vascular‐Targeted Photodynamic Therapy for Port Wine Stains

BACKGROUND Port wine stains (PWS) are congenital capillary malformations of the skin and are difficult to treat without scarring. Since January 1991, our group has performed a new modality of vascular‐targeted photodynamic therapy (PDT) for PWS treatment. OBJECTIVE To summarize our clinical experiences with vascular‐targeted PDT for PWS at Chinese PLA General Hospital. METHODS AND MATERIALS Our group has collected and reviewed retrospective clinical research data of vascular‐targeted PDT for treating PWS since January 1991. RESULTS Clinical studies showed that vascular‐targeted PDT is an effective treatment for all types of PWS. Repetitive treatment sessions were usually needed to obtain a better cosmetic effect. No recurrence was seen in patients followed up for longer than 19 years. There were no significant side effects or adverse reactions. CONCLUSION This new PDT is an effective, safe, and noninvasive modality with no recurrence for PWS, although the protocol for PDT requires further optimization. The authors have indicated no significant interest with commercial supporters.

Imaging port wine stains by fiber optical coherence tomography

We develop a fiber optical coherence tomography (OCT) system in the clinical utility of imaging port wine stains (PWS). We use our OCT system on 41 patients with PWS to document the difference between PWS skin and contralateral normal skin. The system, which operates at 4 frames with axial and transverse resolutions of 10 and 9 mum, respectively, in the skin tissue, can clearly distinguish the dilated dermal blood vessels from normal tissue. We present OCT images of patients with PWS and normal human skin. We obtain the structural parameters, including epidermal thickness and diameter and depth of dilated blood vessels. We demonstrate that OCT may be a useful tool for the noninvasive imaging of PWS. It may help determine the photosensitizer dose and laser parameters in photodynamic therapy for treating port wine stains.

Monitoring Microcirculation Changes in Port Wine Stains During Vascular Targeted Photodynamic Therapy by Laser Speckle Imaging

This study was conducted to test laser speckle perfusion imaging (LSPI) for imaging microcirculation and monitoring microcirculatory changes of port wine stains (PWS) during vascular targeted photodynamic therapy (V‐PDT). Before and 5 min after V‐PDT, PWS lesions and the corresponding contralateral healthy skins of 24 PWS patients were scanned, whereas seven PWS patients were scanned throughout V‐PDT. V‐PDT was conducted immediately after intravenous injection of photocarcinorin (4–5 mg kg−1). A 532 nm laser was used for irradiation (power density: 80–100 mW cm−2, exposure time: 20–50 min). Before V‐PDT, all 24 PWS patients demonstrated a significant difference in perfusion between the PWS lesion and the contralateral healthy control skin (1132 ± 724 and 619 ± 478 PU, respectively, P < 0.01). Five minutes after V‐PDT, the mean perfusion value of the 24 PWS lesions was 1246 ± 754 PU. There was no significant difference compared to the perfusion before V‐PDT (P > 0.05). During V‐PDT, the perfusion of seven PWS patients increased rapidly after initiation of V‐PDT, reached a maximum within 10 min, lasted for several minutes, and slowly returned to a relatively lower level at the end of V‐PDT. On the basis of these results, LSPI is capable of imaging PWS microvasculature and monitoring microvascular reactivity to V‐PDT.

In vitro and in vivo antitumor activity of a novel hypocrellin B derivative for photodynamic therapy

BACKGROUND Photodynamic therapy (PDT) is an approved therapeutic procedure that exerts cytotoxic activity toward tumor cells by irradiating photosensitizers with light exposure to produce reactive oxygen species (ROS). An ideal photosensitizer is a crucial element to PDT. In the current study, we evaluated the photodynamic activity of a novel photosensitizer, the derivative of hypocrellin B (HB), 17-(3-amino-1-pentanesulfonic acid)-substituted hypocrellin B Schiff-base (PENSHB), both in vitro and in vivo. METHODS Physicochemical characteristics of the novel photosensitizer were compared with that of its parent HB. The intracellular distribution of photosensitizers and mitochondrial membrane potential were detected with laser scanning confocal microscopy. The pathway of cell death was analyzed by flow cytometry. The release of proapoptotic proteins was evaluated by Western blot. S180 tumor model was used to evaluate the antitumor effects of PENHB-mediated PDT. RESULTS Compared with its parent HB, water solubility of the derivative was improved enormously (6.6 mg/ml vs. 4.6 μg/ml), rendering its intravenous injection feasible without auxiliary solvent. The derivative had better PDT effect than HB in vitro under similar dark cytotoxicity. Moreover, PENSHB-mediated PDT was able to induce mitochondrial inner membrane permeabilisation, cytochrome c release, caspase-3 activation and subsequent apoptotic death. In vivo study showed that more than half of tumor bearing mice were cured by PENSHB-mediated PDT. CONCLUSIONS In vitro and in vivo studies suggest that PENSHB is an effective photosensitizer for PDT to tumors. Therefore, PENSHB as a novel photosensitizer has a good prospect of clinical application.

Choosing optimal wavelength for photodynamic therapy of port wine stains by mathematic simulation

Many laser wavelengths have been used in photodynamic therapy (PDT) for port wine stains (PWS). However, how these wavelengths result in different PDT outcomes has not been clearly illuminated. This study is designed to analyze which wavelengths would be the most advantageous for use in PDT for PWS. The singlet oxygen yield in PDT-treated PWS skin under different wavelengths at the same photosensitizer dosage was simulated and the following three situations were simulated and compared: 1. PDT efficiency of 488, 532, 510, 578, and 630 nm laser irradiation at clinical dosage (100 mW∕cm(2), 40 min); 2. PDT efficiency of different wavelength for PWS with hyperpigmentation after previous PDT; 3. PDT efficiency of different wavelengths for PWS, in which only deeply located ectatic vessels remained. The results showed that singlet oxygen yield is the highest at 510 nm, it is similar at 532 nm and 488 nm, and very low at 578 nm and 630 nm. This result is identical to the state in clinic. According to this theoretical study, the optimal wavelength for PDT in the treatment of PWS should near the absorption peaks of photosensitizer and where absorption from native chromophores (haemoglobin and melanin) is diminished.

Imaging of skin microvessels with optical coherence tomography: potential uses in port wine stains.

The knowledge of vascular structures of port wine stains (PWSs) may be useful to select treatment doses and improve therapeutic efficacy. Biopsies are impractical to implement, therefore, it is necessary to develop non-invasive techniques for morphological evaluation. This study aimed to evaluate the application of a novel optical coherence tomography (OCT) system to characterize the vascular structures of PWSs. First, OCT images were obtained from the skin of healthy rabbit ears and compared with the histopathological images. Second, OCT was used to document the differences between PWS lesions and contralateral normal skin; the size and depth of the vascular structures of two clinical types of PWSs were measured and statistically analyzed. The dermal blood vessels of healthy rabbit ears were clearly distinguished from other tissue. There was no statistical difference between the vascular diameter or depth measured by OCT images and histopathological sections (P>0.05). The OCT images of the PWSs could be distinguished from normal skin. There was no statistical difference in the depth of vessels between the purple-type and the proliferative-type PWSs (P>0.05), while there was statistical difference in the diameter of vessels between them (P<0.01). Therefore, OCT is a promising, real-time, in vivo and non-invasive tool with which to characterize the vascular structures of PWSs.

Influence of drug-light-interval on photodynamic therapy of port wine stains—Simulation and validation of mathematic models

OBJECTIVES We established mathematical models of photodynamic therapy (PDT) on port wine stains (PWS) to observe the effect of drug-light-interval (DLI) and optimize light dose. MATERIALS AND METHODS The mathematical simulations included determining (1) the distribution of laser light by Monte Carlo model, (2) the change of photosensitizer concentration in PWS vessels by a pharmacokinetics equation, (3) the change of photosensitizer distribution in tissue outside the vessels by a diffuse equation and photobleaching equation, and (4) the change of tissue oxygen concentration by the Ficks law with a consideration of the oxygen consumption during PDT. The concentration of singlet oxygen in the tissue model was calculated by the finite difference method. To validate those models, a PWS lesion of the same patient was divided into two areas and subjected to different DLIs and treated with different energy density. The color of lesion was assessed 8-12 weeks later. RESULTS The simulation indicated the singlet oxygen concentration of the second treatment area (DLI=40 min) was lower than that of the first treatment area (DLI=0 min). However, it would be increased to a level similar to that of the first treatment area if the light irradiation time of the second treatment area was prolonged from 40 min to 55 min. Clinical results were consistent with the results predicted by the mathematical models. CONCLUSIONS The mathematical models established in this study are helpful to optimize clinical protocol.

New optional photodynamic therapy laser wavelength for infantile port wine stains: 457 nm

To expand the optional laser wavelengths of photodynamic therapy (PDT) for port wine stain (PWS), the feasibility of applying a 457 nm laser to the PDT for infantile PWS was analyzed by mathematical simulation and was validated by clinical experiment. Singlet oxygen yield of 457 nm PDT or 532 nm PDT in an infantile PWS model and an adult PWS model was theoretically simulated. Fifteen PWS patients (14 infants and 1 adult) with 40 spots were treated with 457 nm (20 spots) and 532 nm (20 spots), respectively, in two PDT courses. Simulation results showed that under the same power density and irradiation time, singlet oxygen yield of 457 nm PDT and 532 nm PDT are similar in infantile PWS vessels. Yet, in adult PWS vessels, singlet oxygen yield of 457 nm PDT is lower than 532 nm PDT. Clinical outcomes showed that no statistic difference existed between 457 nm PDT and 532 nm PDT for infantile PWS. The result of this study suggested that 457 nm wavelength laser has the potential to be applied in PDT for infantile PWS.

Photodynamic therapy for port wine stains assisted by a novel robotic system

Port wine stains (PWS) is a vascular malformation consisting of dilated capillaries in the superficial dermis. Photodynamic therapy (PDT) is an effective approach in the treatment of PWS. However, the procedure of treatment is a low efficient and hard work, as the doctor need to hold laser fiber to irradiate for 20 min to 50 min per lesion. So an assisted novel robotic system was developed to instead part of doctors work. The robotic system consisted of 7 degrees of freedom, in which there were 5 passive joints and 2 active joints. Binocular surveillance system was used as guidance for the robot. Clinical trial compared 20 patients (38 lesions) treated by the robotic system with another 20 patients (38 lesions) treated by a doctor. The patients in both groups were injected intravenously with photosensitizer (PSD-007, 4-5mg/kg) and irradiated with 532 nm laser (100mW/cm2, 120-300J/cm2) immediately. Both groups had same good therapeutic results. The robotic system is helpful in the PWS-PDT and hopefully would become a part of PWS therapy machine in the future.