Fluorescence diagnosis in actinic keratosis and squamous cell carcinoma.

BACKGROUND: As different tissue types have distinct capabilities to accumulate protoporphyrin IX, fluorescence diagnosis with aminolevulinic acid-induced porphyrins (FDAP) could be used to discriminate between different types of tissue. Previous results demonstrated higher fluorescence ratios in squamous cell carcinoma (SCC) compared with actinic keratoses (AKs). OBJECTIVES: The lesional : non-lesional fluorescence ratio of AKs was compared with the ratio of SCC. Other factors influencing macroscopic fluorescence were also assessed, including stratum corneum thickness, which has been demonstrated to account for heterogeneous fluorescence in psoriasis and in AKs. METHODS: After 1 week of keratolytic pretreatment, FDAP was performed in 13 patients with 36 lesions suspected for AK or SCC. Biopsies were taken for histopathological diagnosis and measurement of stratum corneum thickness. RESULTS: No significant differences were found in the fluorescence ratio (lesional : non-lesional skin) between AKs and SCCs, although macroscopic fluorescence was significantly higher in Bowen's disease and micro-invasive SCCs. CONCLUSIONS: There could be a potential applicability of FDAP to differentiate premalignant lesions with a tendency to progress into SCC and squamous cutaneous lesions already progressing into early invasive cancer from other squamous cutaneous (pre)malignancies. The amount of hyperkeratosis, invasiveness and degree of differentiation seem to be responsible for variations in fluorescence intensity.

Clinical and histological effects of blue light on normal skin.

INTRODUCTION: Phototherapy with visible light is gaining interest in dermatological practice. Theoretically, blue light could induce biological effects comparable to ultraviolet A (UVA) radiation. OBJECTIVES: To study the effects of blue light on normal skin in terms of photodamage, skin ageing and melanogenesis. METHODS: Eight healthy volunteers were included and irradiation with visible blue light was given on five consecutive days. Skin biopsies were analysed with respect to photodamage (p53, vacuolization, sunburn cells), skin ageing (elastosis, MMP-1) and melanogenesis (Melan-A). RESULTS: No inflammatory cells and sunburn cells were visible before or after irradiation. A significant increase in the perinuclear vacuolization of keratinocytes was demonstrated during treatment (P=0.02) with a tendency towards significance after cessation of treatment (P=0.09). No significant change in p53 expression was seen. Signs of elastosis and changes in MMP-1 expression were absent. Minimal clinical hyperpigmentation of the irradiated skin was confirmed histologically with a significant increase in Melan-A-positive cells (P=0.03). CONCLUSIONS: Visible blue light, as given in the present study, does not cause deoxyribonucleic acid damage or early photo-ageing. The biological effects of blue light on normal skin are transient melanogenesis and inexplicable vacuolization without resulting apoptosis. In conclusion, the (short-term) use of visible blue light in dermatological practice is safe.

Ultraviolet A phototherapy for sclerotic skin diseases: a systematic review.

BACKGROUND: Ultraviolet (UV) A-1 phototherapy is now available for a variety of skin diseases. Increasingly since 1995, there have been investigations of the efficacy of UVA-1 (340-400 nm) therapy for sclerotic skin diseases. Most studies undertaken treated patients who had localized scleroderma, but UVA-1 phototherapy is currently also used for other sclerotic skin conditions. OBJECTIVE: We sought to assess the efficacy, biological effects, and side effects of UVA-1 in a variety of sclerotic skin diseases (localized scleroderma, eosinophilic fasciitis, chronic graft-versus-host disease, lichen sclerosus et atrophicus, scleredema adultorum, necrobiosis lipoidica, POEMS disease, pansclerotic porphyria cutanea tarda, and drug-induced scleroderma-like disorders). METHODS: The authors searched for publications dated between January 1996 and November 2007 in the computerized bibliographic database, PubMed. PubMed was searched using medical subject heading terms and open searches to retrieve the latest reports. RESULTS: The evidence based on research concerning the effect of full-spectrum UVA (320-400 nm) and UVA-1 on these skin diseases is still growing, and appears promising. Up until now, good results are shown for all different doses (low, medium, and high) UVA-1 and UVA. There are insufficient data regarding use of high-dose UVA-1 and there are no comparative studies to make a clear assessment regarding the superiority of low-, medium-, or high-dose UVA-1 therapy. Although UVA-1 has various effects on, for instance, fibroblasts and inflammatory cells, the precise mode of action remains obscure. The main short-term side effects of UVA-1 therapy are erythema, pruritus, xerosis cutis, tanning, and recrudescence of herpes simplex infection. More studies are warranted to investigate the potential long-term risk of photoaging and skin cancer. Currently, UVA-1 is considered to be less carcinogenic than psoralen plus UVA (PUVA). LIMITATIONS: Because of the limited availability of randomized controlled trials and large cohort studies, it is difficult to draw firm conclusions on the long-term efficacy, optimum dose, and best treatment regimens for UVA-1 when administered to patients with sclerosing skin disorders. CONCLUSIONS: Full-spectrum UVA and UVA-1 phototherapy seem effective in the treatment of sclerotic skin diseases based on data retrieved from the literature. UVA-1 treatment can shorten the active period of localized scleroderma and pseudoscleroderma and prevent further disease progression, including contractures. Further investigations will be needed to determine any additional biological effects of UVA-1. Although long-term side effects are not yet known, UVA-1 might develop into a promising beneficial and well-tolerated treatment in the therapeutic armamentarium for sclerotic skin diseases. Long-term studies in large groups of patients are clearly needed.

Clinical implementation of 3D printing in the construction of patient specific bolus for electron beam radiotherapy for non-melanoma skin cancer.

BACKGROUND AND PURPOSE: Creating an individualized tissue equivalent material build-up (i.e. bolus) for electron beam radiation therapy is complex and highly labour-intensive. We implemented a new clinical workflow in which 3D printing technology is used to create the bolus. MATERIAL AND METHODS: A patient-specific bolus is designed in the treatment planning system (TPS) and a shell around it is created in the TPS. The shell is printed and subsequently filled with silicone rubber to make the bolus. Before clinical implementation we performed a planning study with 11 patients to evaluate the difference in tumour coverage between the designed 3D-print bolus and the clinically delivered plan with manually created bolus. For the first 15 clinical patients a second CT scan with the 3D-print bolus was performed to verify the geometrical accuracy. RESULTS: The planning study showed that the V85% of the CTV was on average 97% (3D-print) vs 88% (conventional). Geometric comparison of the 3D-print bolus to the originally contoured bolus showed a high similarity (DSC=0.89). The dose distributions on the second CT scan with the 3D print bolus in position showed only small differences in comparison to the original planning CT scan. CONCLUSIONS: The implemented workflow is feasible, patient friendly, safe, and results in high quality dose distributions. This new technique increases time efficiency.

The clinical efficacy of topical methyl-aminolevulinate photodynamic therapy in moderate to severe actinic keratoses of the face and scalp.

INTRODUCTION: Since actinic keratoses (AKs) often appear in areas with field cancerization, photodynamic therapy (PDT) may have significant advantages over the standard treatment options. OBJECTIVES: Clinical efficacy of PDT with topical methyl aminolevulinate (MAL-PDT) in field cancerization was evaluated with respect to the number of AKs and photodamage. METHODS: A total of 14 patients with 223 AKs on the face or scalp were treated with MAL-PDT. Two treatments with a 3-monthly interval were given. At baseline, before the second treatment and 3 months after the end of therapy, the number of AKs were counted and photodamage was assessed with respect to skin roughness, hyperpigmentation, hypopigmentation, scarring, atrophy, telangiectasia and wrinkling. RESULTS: Complete clearance was reached in patients with a moderate degree of actinic damage, whereas a severe degree of field cancerization demonstrated only partial clearance. The global score for photodamage improved significantly. After the follow-up period, none of the patients reaching clearance had developed relapsing or new AKs. CONCLUSIONS: MAL-PDT induces a high clearance rate of AKs, dependent on the degree of field cancerization, with a good improvement in photodamage and prevention of developing new AKs. Thus, more PDT sessions are needed in patients with a severe degree of field cancerization.

The effects of keratolytic pretreatment prior to fluorescence diagnosis and photodynamic therapy with aminolevulinic acid-induced porphyrins in psoriasis.

BACKGROUND: Psoriasis lesions accumulate protoporphyrin IX (PpIX) with a variable distribution within plaques due to variations in hyperkeratosis causing differences in penetration of cream or light. OBJECTIVES: To study the effects of different keratolytic pretreatments in PpIX-induced fluorescence diagnosis (FDAP) and during photodynamic therapy (PDT). METHODS: Two psoriasis plaques of 10 patients were treated with either topical retinoic acid or with a hydrocolloid dressing. The hydrocolloid dressing gave the best results. Subsequently, two different contralateral plaques of eight patients were pretreated with a hydrocolloid dressing or the standard pretreatment, salicylic acid in petrolatum, during the 6 weeks of PDT. Biopsies were investigated with respect to stratum corneum thickness, proliferation, differentiation and inflammation. RESULTS: Irritation and point bleedings were noticed after retinoic acid. A hydrocolloid dressing induced the best clinical improvement. Therefore, it was used as alternative pretreatment for psoriasis prior to PDT. We observed significant clinical and immunohistochemical improvement of psoriasis in the salicylic acid as well as the hydrocolloid dressing pretreated plaques. CONCLUSIONS: Salicylic acid in petrolatum and a hydrocolloid dressing prior to FDAP and PDT induce improvement of hyperkeratosis. Thus, a hydrocolloid dressing is a good alternative to the current keratolytic pretreatment regime.