Clinical evaluation of a short illumination duration (1 hour) when performing photodynamic therapy of actinic keratosis using the Dermaris light source.

BACKGROUND: Photodynamic therapy (PDT) using daylight as the photoactivating light source (DL-PDT) is an effective treatment for actinic keratosis (AK). Among the artificial daylight sources, the Dermaris (Surgiris, Croix, France) is specially designed for SDL-PDT (simulated daylight PDT) of AK. To perform the PDT session, a long duration (2.5 h) and low-intensity light exposure (2.9 mw/cm²) is used. This long duration is considered as a major limitation by both the patient and the dermatologist. OBJECTIVES: The paper aims to report the clinical outcomes of SDL-PDT using the Dermaris in patients treated for AK lesions of the scalp at our medical dermatology center using only one hour low-intensity light exposure. METHODS: Thirty patients (19 males, 11 females), mean age: 72.8 ± 9.3, with phototype 1 (11 patients), with phototype 2(17 patients) and phototype 3 (2 patients), with grade I-II AK of the scalp were treated with a drug-light interval (DLI) of 10 min and a light exposure of 1 h. The cure rate of AK lesions at six months after the treatment was determined. Erythema, crusts, discomfort and during or/and post the treatment were also evaluated. RESULTS: In total, 293 AK were treated. Six months following treatment, the cure rate of patients was 93%. Pain score reported after the first PDT session was from 0 to 1 on a visual analogue scale (VAS) ranging from 0 to 10. Erythema was observed in 28 patients and lasted 3 days, crusts were seen in 19 patients. Discomfort was as mild or less in more than 97% of patients. CONCLUSIONS: the shortening of the exposure time to one hour does not modify the efficacy of the SDL-PDT using the Dermaris. This observation is in agreement with recent published data demonstrating that PDT can be performed successfully with half the illumination time used in daylight PDT today. Besides, this clinical study confirmed that SDL-PDT is an effective and nearly painless treatment with minimal side effects for patients with AK lesions of the scalp.

[Flap harvest training on a new ultrarealistic simulation model: In-training operator feedback about a pulsating reperfused and reventilated cadaver Simlife®]. / Prélèvement des lambeaux sur sujet anatomique et nouveau modèle de simulation ultra-réaliste : retour d'expérience d'un opérateur en formation sur corps reperfusé pulsatile et reventilé Simlife®.

INTRODUCTION: The anatomical subject is still a key element to learn complex procedures in plastic surgery. We present here the evaluation of an in-training operator on a SIMLIFE® model, hyper realistic model consisting in human bodies donated to science equipped with pulsating recirculation and reventilation device. MATERIAL AND METHODS: From February 2019 to October 2019, 8 forearm flaps with radial proximal pedicle were harvested by the learner on a SIMLIFE® model. Conditions were as close as possible to the operating room : asepsy, sterile draping, assistant and instrumentation including electrocoagulation. RESULTS: The procedure was decomposed in 13 distinct steps. Mean total surgery time was 90,5±11,62minutes. There was only one case of arterial pedicle lesion resulting in major blood leak. Bleeding was measured by fake blood loss from the SIMLIFE® console. Mean intraoperatoy bleeding was 171±108 milliliters. We review pros and cons of this new technology particulary suited for complex plastic and reconstructive surgery training. CONCLUSION: Using SIMLIFE® technology we have a new mean to train for complex procedures in plastic and reconstructive surgery. This new technology could be applied to numerous other surgical procedures. Broader applications are still limited by cost and cadaver use legislation.

Real-life evaluation of the treatment of actinic keratoses by textile photodynamic therapy (FLUXMEDICARE® device).

INTRODUCTION: Actinic keratoses (AK) are a common precancerous skin condition in dermatology practice. Photodynamic therapy (PDT) with ALA or MAL is an effective but painful treatment of fields of cancerization particularly when conventional illumination sources and irradiation rates are used. Two prior studies showed that illumination with textile PDT was not inferior to conventional PDT. FLUXMEDICARE® (FLX-PDT) is the first medical device marketed with textile based lighting . We performeda real-life study to evaluate efficacy and tolerance of this device. METHODS: We carried out a single-center retrospective study. We collected data from patients treated with FLX-PDT with MAL for AKs localized on scalp and temples between November 2018 and November 2019. The primary endpoint was complete clearance rate (CR) at 3 months-follow up. RESULTS: Data of 39 patients were reviewed in the study, with a total of 417 AKs. The CR rate was 72.6 % (95 %CI 67.9-77.0) at 3 months-follow up and 67.5 % (95 %CI 61.2-73.3) at 6 months-follow up. The median pain felt during the session was 0 and there wasn't erythema after the session for 64.1 %. CONCLUSION: Our real-life study confirms efficacy and safety of textile PDT by FLUXMEDICARE device in the treatment of scalp and temples AKs, with excellent tolerance and minimal pain reported.

The conventional protocol vs. a protocol including illumination with a fabric-based biophotonic device (the Phosistos protocol) in photodynamic therapy for actinic keratosis: a randomized, controlled, noninferiority clinical study.

BACKGROUND: Topical photodynamic therapy (PDT) using methyl aminolaevulinate is a noninvasive treatment option suitable to treat clinical and subclinical actinic keratosis (AK) over a large area (field cancerization). The most widely used, conventional protocol in Europe includes illumination with a red-light lamp. This illumination commonly causes pain, and patients often cannot complete the treatment. OBJECTIVES: The aims of this paper are twofold. The first aim is to introduce a novel protocol, the Phosistos protocol (P-PDT), which includes illumination with a fabric-based biophotonic device. The second and major aim is to assess the noninferiority, in terms of efficacy for PDT of AK, of P-PDT compared with the conventional protocol (C-PDT). METHODS: A randomized, controlled, multicentre, intraindividual clinical study was conducted. Forty-six patients with grade I-II AK of the forehead and scalp were treated with P-PDT on one area (280 AK lesions) and with C-PDT on the contralateral area (280 AK lesions). The primary end point was the lesion complete response (CR) rate at 3 months, with an absolute noninferiority margin of -10%. Secondary end points included pain scores, incidence of adverse effects and cosmetic outcome. RESULTS: Three months following treatment, the lesion CR rate of P-PDT was noninferior to that of C-PDT (79·3% vs. 80·7%, respectively; absolute difference -1·6%; one-sided 95% confidence interval -4·5% to infinity). The noninferiority of P-PDT to C-PDT in terms of the lesion CR rate remained at the 6-month follow-up (94·2% vs. 94·9%, respectively; absolute difference -0·6%; one-sided 95% confidence interval -2·7% to infinity). Moreover, the pain score at the end of illumination was significantly lower for P-PDT than for C-PDT (mean ± SD 0·3 ± 0·6 vs. 7·4 ± 2·3; P < 0·001). CONCLUSIONS: P-PDT is noninferior to C-PDT in terms of efficacy for treating AK of the forehead and scalp and resulted in much lower pain scores and fewer adverse effects. What's already known about this topic? Topical photodynamic therapy using methyl aminolaevulinate is effective for treating actinic keratosis. In Europe, the conventional protocol involves illumination with a red-light lamp. Unfortunately, pain is often experienced by patients undergoing this protocol. An alternative protocol that uses daylight illumination has recently been shown to be as effective as the conventional protocol while being nearly painless. However, this alternative protocol can be conducted only in suitable weather conditions. What does this study add? The Phosistos protocol is demonstrated to be as effective as the conventional protocol, nearly as painless as the daylight protocols and suitable year round for treatment of actinic keratosis.

Photodynamic therapy for atherosclerosis. The potential of indocyanine green.

AIM: The aim of this article is to summarize and review the use of photodynamic therapy for the treatment of atherosclerotic plaque and the prevention of intimal hyperplasia. Different photosensitizers are discussed and more specifically the role of indocyanine green as a potential photosensitizer. METHODS: Literature search with focus on the use of photodynamic therapy in atherosclerosis, the mechanism of action and the different photosensitizers for photodynamic therapy. RESULTS: In-vitro and in-vivo studies confirm the possibilities of using photodynamic therapy for the treatment of atherosclerosis and the prevention of restenosis. Insufficient specificity in the accumulation of photosensitizer and thus phototoxicity, remains an important problem. Indocyanine green is a photosensitizer with features in favor of photodynamic therapy. Results obtained so far of photodynamic therapy with indocyanine green point towards the potential of indocyanine green as a photosensitizer in photodynamic therapy for atherosclerosis. CONCLUSION: Photodynamic therapy is a promising tool for treating atherosclerosis. Many of the studied photosensitizers have toxic effects. Indocyanine green might be a good photosensitizer for the use of photodynamic therapy in atherosclerosis. These data justify further research to the use of indocyanine green as a photosensitizer in the treatment of atherosclerotic plaque both de novo or in restenotic lesions.

Photodynamic therapy for actinic keratosis of the forehead and scalp: a randomized, controlled, phase II clinical study evaluating the noninferiority of a new protocol involving irradiation with a light-emitting, fabric-based device (the Flexitheralight protocol) compared with the conventional protocol involving irradiation with the Aktilite CL 128 lamp.

BACKGROUND: Photodynamic therapy (PDT) is an effective treatment for actinic keratosis (AK), particularly for patients with large areas of field cancerization. Among the approved protocols in Europe, the most widely used requires irradiation with the Aktilite CL 128 lamp. However, pain during irradiation and the suboptimal adaptability of the lamp relative to the treatment area are two limiting factors of this protocol. To overcome these limits, a new protocol (referred to as the Flexitheralight protocol) involving irradiation with a light-emitting, fabric-based device was developed. OBJECTIVES: This paper aims to assess the noninferiority, in terms of PDT efficacy for treating AK, of the Flexitheralight protocol compared with the conventional protocol, which requires irradiation with the Aktilite CL 128 lamp. METHODS: A monocentric, randomized, controlled, phase II clinical study was performed. Twenty-five patients with grade I-II AKs of the forehead and scalp were treated with methyl aminolaevulinate PDT in two symmetrical areas. One area was treated with the conventional protocol (n = 154 AKs), whereas the other area was treated with the Flexitheralight protocol (n = 156 AKs). The primary end-point was the lesion complete response (CR) rate at 3 months (an absolute noninferiority margin of -10% was used). The secondary end-points included patient-reported pain at the end of the irradiation. RESULTS: At 3 months, the lesion CR rate with the Flexitheralight protocol was noninferior to that obtained with the conventional protocol (66·0% vs. 59·1%, respectively; absolute difference, 6·9%; 95% confidence interval -0·6% to 14·5%). Patient-reported pain was significantly lower with the Flexitheralight protocol than with the conventional protocol (mean ± SD: 0·4 ± 0·6 vs. 5·0 ± 2·6; P < 0·0001). CONCLUSIONS: The Flexitheralight protocol is noninferior in terms of efficacy and superior in terms of tolerability to the conventional protocol for treating AKs of the forehead and scalp.

[Microscopic peritoneal metastases of epithelial ovarian cancers. Clinical relevance, diagnostic and therapeutic tools]. / Métastases péritonéales microscopiques des cancers épithéliaux de l'ovaire. Pertinence clinique, outils diagnostiques et thérapeutiques.

Understanding the biology and progression mechanisms of peritoneal metastases in ovarian epithelial cancers (EOC) is important because peritoneal carcinomatosis is present or will occur during surveillance of a majority of patients. Despite the clinical remission achieved after complete macroscopic cytoreductive surgery and platinum-based chemotherapy, 60% of patients will develop peritoneal recurrence. This suggests that microscopic lesions, which are not eradicated by surgery may be present and may participate in the mechanisms leading to peritoneal recurrence. This paper discusses current available data on microscopic peritoneal metastases, their diagnosis and their treatment. We reviewed all publications dealing with microscopic peritoneal metastases of EOC between 1980 and 2017. The most recent and most relevant publications dealing with the treatment modalities of these metastases were selected. Peritoneal and epiploic microscopic localizations would occur in 1.2 to 15.1% of cases at early-stage and are not treated during conventional surgery. They could represent a potential therapeutic target. Local treatments (intraperitoneal chemotherapy, photodynamic therapy, fluorescence-guided surgery) seem to be necessary in addition to surgery and chemotherapy and may help reduce the risk of peritoneal recurrence. The place of these treatments in the management of EOC remains to be defined by subsequent researches.

Is Salvage of Recently Infected Breast Implant After Breast Augmentation or Reconstruction Possible? An Experimental Study.

INTRODUCTION: The reinsertion of an infected implant when peri-prosthetic infection occurs early after breast augmentation or breast reconstruction remains controversial. In this experimental study, the authors tried to remove bacteria, and their biofilm, from the colonized surface of breast prostheses, without damaging their integrity. MATERIALS AND METHODS: A total of 112 shell samples of silicone breast prostheses, smooth (SPSS) and textured (TPSS), were colonized by S. epidermidis (SE) or S. aureus (SA) strains, all able to produce biofilms. After 15 days, all the samples were removed from the contaminated culture broth and constituted 4 groups of 20 contaminated samples: SPSS/SE (group I), SPSS/SA (group II), TPSS/SE (group III), TPSS/SE (group IV). In another group-group SEM-, 16 colonized samples were used for documentation with scanning electron microscopy (SEM). The remaining 16 samples were used to test the limits of detection of the sterility test. All samples of groups I-IV and 8 samples of group SEM were « washed ¼ with a smooth brush in a povidone-iodine bath and rinsed with saline solution. A subset of the washed samples was sent for SEM and the others were immersed in sterile broth and were incubated at 35 °C for 3 weeks (groups I-IV). RESULTS: Fifteen days after contamination, all the samples in groups I-IV were colonized. In the SEM group, SEM images attested to the presence of bacteria in biofilm attached to the shells. After cleaning, SEM did not reveal any bacteria and there was no visible alteration in the outer structure of the shell. Sterility tests performed after decontamination in groups I-IV remained negative for all the samples. CONCLUSION: Breast prostheses recently contaminated with Staphylococci, frequently involved in peri-prosthetic breast implant infection and capable of producing biofilms, can be efficiently decontaminated by the procedure used in this study. Our decontamination procedure did not alter the surface structure of the prostheses. This decontamination procedure could allow reinsertion of an infected implant when peri-prosthetic infection occurs early after breast augmentation or breast reconstruction and when a salvage procedure is indicated. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

[Intraperitoneal photodynamic therapy for peritoneal metastasis of epithelial ovarian cancer. Limits and future prospects]. / Traitement des métastases péritonéales des cancers épithéliaux de l'ovaire par thérapie photodynamique. Limites et perspectives.

High peritoneal recurrence rate in advanced epithelial ovarian cancer after complete macroscopic cytoreductive surgery and platinum-based chemotherapy, raises the issue of peritoneal microscopic disease management and requires the development of additional locoregional treatment strategies. Photodynamic therapy is an effective treatment already applied in other medical and surgical indications. After administration of a photosensitizer which accumulates in cancer cells, illumination with a light of adequate wavelength may induce photochemical reaction between photosensitizer and tissue oxygen which lead to reactive oxygen species production and cytotoxic phenomenon. Photodynamic therapy's ability to treat superficial lesions disseminated on large area makes it an excellent candidate to insure destruction of microscopic peritoneal metastases in addition to macroscopic cytoreductive surgery in order to decrease peritoneal recurrence rate. Development of intraperitoneal photodynamic therapy has been limited by its poor tolerance related to the lack of specificity of photosensitizers and the location of the metastases in proximity to adjacent intraperitoneal organs. Our aim is to review clinical data concerning intraperitoneal photodynamic therapy and epithelial ovarian cancer to identify the limits of this strategy and to provide solutions which may be applied to solve these barriers and enable safe and effective treatment. Targeted photosensitizers and innovative illumination solutions are mandatory to continue research in this field and to consider the feasibility of clinical trials.

[Specific folic-acid targeted photosensitizer. The first step toward intraperitoneal photodynamic therapy for epithelial ovarian cancer]. / Photosensibilisateur spécifique pour la thérapie photodynamique ciblée des métastases péritonéales des cancers ovariens.

OBJECTIVE: Epithelial ovarian cancer (EOC) management remains association of debulking surgery in combination with platinum-based chemotherapy. Sixty percent of women with EOC considered in remission will develop recurrent disease. An option to improve the completion of cytoreductive surgery may be the use of photodynamic therapy to induce necrosis of peritoneal metastases. A limit of this technique was the toxicity induced by the lack of specificity of old-generation photosensitizer (PS) for tumor tissue if the light could not be specifically applied. To solve this problem, a solution is the design of selective PS. Folate receptor is a promising target for EOC targeted therapy. We present preclinical results concerning properties of a folic-acid targeted photosensitizer. METHOD: Preclinical studies have been performed in vitro on murine and human cell lines of EOC and in vivo with a preclinical model of peritoneal carcinomatosis (Fisher F344 rat/NuTu-19 cell line). They aimed to precise the ability of PS to target specifically tumor tissue, to emit specific fluorescence, and to obtain cell death. RESULTS: Tissue quantification of the PS showed specific incorporation of the folate-targeted PS within tumor tissue. Specificity for ovarian cancer metastases is better than previously reported with others photosensitizers (tumor-to-normal tissue ratio 9.6). We could detect specific fluorescence in vitro and in vivo on peritoneal metastases. Folic-acid targeted PDT allows to obtain human EOC cells death. CONCLUSION: Specific PS may allow the development of efficient and safe intraperitoneal PDT procedure, which could play a role in the prevention of EOC peritoneal recurrences.

Gland and Zonal Segmentation of Prostate on T2W MR Images.

For many years, prostate segmentation on MR images concerned only the extraction of the entire gland. Currently, in the focal treatment era, there is a continuously increasing need for the separation of the different parts of the organ. In this paper, we propose an automatic segmentation method based on the use of T2W images and atlas images to segment the prostate and to isolate the peripheral and transition zones. The algorithm consists of two stages. First, the target image is registered with each zonal atlas image then the segmentation is obtained by the application of an evidential C-Means clustering. The method was evaluated on a representative and multi-centric image base and yielded mean Dice accuracy values of 0.81, 0.70, and 0.62 for the prostate, the transition zone, and peripheral zone, respectively.

Computer-aided analysis of prostate multiparametric MR images: an unsupervised fusion-based approach.

OBJECTIVE: The aim of this study is to provide an automatic framework for computer-aided analysis of multiparametric magnetic resonance (mp-MR) images of prostate. METHOD: We introduce a novel method for the unsupervised analysis of the images. An evidential C-means classifier was adapted for use with a segmentation scheme to address multisource data and to manage conflicts and redundancy. RESULTS: Experiments were conducted using data from 15 patients. The evaluation protocol consisted in evaluating the method abilities to classify prostate tissues, showing the same behaviour on the mp-MR images, into homogeneous classes. As the actual diagnosis was available, thanks to the correlation with histopathological findings, the assessment focused on the ability to segment cancer foci. The method exhibited global sensitivity and specificity of 70 and 88 %, respectively. CONCLUSION: The preliminary results obtained by these initial experiments showed that the method can be applied in clinical routine practice to help making decision especially for practitioners with limited experience in prostate MRI analysis.

[Establishment of a keloid model by transplanting human keloid onto the backs of nude mice]. / Mise au point d'un modèle animal original de cicatrice chéloïde.

Keloid scar is a proliferative healing dysfunction formed by an excessive build-up of collagen fibers on the dermis. It is responsible of aesthetic and functional disabilities. There is no ideal treatment and recurrence occurs very often. Keloid scars occur only to human, that's why animal model needs to be made to study this pathology and new treatments. Few models have been described using human keloid scars implanted into subcutaneous tissue of nude mice or rat. To allow study of topical and laser treatment we have developed a new animal model using human keloid scar fragment with epidermal and dermal tissue implanted into back of nude mice like a full thickness skin graft. Keloid fragments from five donors have been grafted onto 40 nudes mice. Macroscopic and microscopic studies have been made at day 28, 56, 84 and 112. We observed integration of the fragments in all cases. Hyalinized collagen bundles were observed in all implant biopsies confirming the stability of the keloid architecture within 112 days. This model is easily reproducible and allows the study of topical treatment and laser due to the accessibility of the keloid.

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.

Iron overload of hematological origin: validation of a screening procedure for cardiac overload by MRI in routine clinical practice.

PURPOSE: Screening for cardiac iron overload is generally done by magnetic resonance imaging (MRI) and demonstrated by a shortening of the myocardial T2* below 20 ms at 1.5 Tesla. This measurement was validated with a specific sequence and the CMRTools(®) calculation software (reference technique). The objective of this study was to validate the use of sequences and software programs that are available in routine clinical practice to screen for iron overload. MATERIAL AND METHODS: First, a phantom of 11 tubes with a T2* between 4 and 33 ms was tested at three sites that had MRI machines of different brands. Second, the myocardial T2* values of 75 patients were measured in routine clinical practice using two methods. The first method used the reference sequence specially installed in the machines associated with the CMRTool software. The second method used the standard acquisition sequences available in the machines followed by calculation on a computer spreadsheet. RESULTS: In the phantom, the mean of the differences in T2* between each machine was 0.6 ms. Thirteen patients had a lowered T2* value with the reference technique. Three cases were poorly classified using the routine technique and corresponded with false positives of low overload (T2* between 18 and 20 ms). CONCLUSION: Screening for myocardial iron overload can be done by MRI by using sequences and calculation software available in routine clinical practice during the same examination as the one for the evaluation of hepatic iron overload.