Clinical, histopathological and immunohistochemical assessment of human skin field cancerization before and after photodynamic therapy

Szeimies, R.–M.; Torezan, Luís; Niwa, Ane Beatriz Mautari; Valente, Neusa Yuriko Sakai; Unger, Petra; Kohl, Elisabeth; Schreml, Stephan; Babilas, Philipp; Karrer, Sigrid; Festa-Neto, Cyro

doi:10.1111/j.1365-2133.2012.10887.x

Cited by 122 publications

(138 citation statements)

References 35 publications

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“…According to this concept of field change, the clinically inconspicuous tissue between visible AK lesions is in all likelihood interspersed with UV-mutated clones. These can potentially sustain and aggravate the disease state, if only visible lesions are treated [26,27]. In addition, it has been shown that mild AKs (grade I) are the most common lesion associated with invasive SCC [12,13].…”

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confidence: 99%

A review of BF-200 ALA for the photodynamic treatment of mild-to-moderate actinic keratosis

Reinhold¹

2017

Future Oncol.

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BF-200 ALA is a combination of a nanoscale-lipid vesicle formulation and the prodrug 5-aminolevulinic acid (5-ALA). The nanoemulsion stabilizes the prodrug and enhances its penetration through the stratum corneum. It has shown excellent therapeutic results in both lesion and field-directed photodynamic therapy of actinic keratosis (AK). AK is an early form of epidermal neoplasia and a precursor of invasive cutaneous squamous cell carcinoma. It is characterized by the combination of visible neoplastic lesions and surrounding tissue also harboring tumorigenic UV-induced mutations: a concept called field cancerization. A selective, field-directed treatment is ideal to meet the requirements of field change. Here, we review the clinical data on BF-200 ALA for AK along with a summary of molecular mechanisms and future perspectives. Actinic keratosis (AK), also known as solar keratosis, is caused by chronic exposure to sunlight or other ultraviolet light sources [1,2] and may progress to invasive squamous cell carcinoma (SCC) [3]. It is the most common lesion with malignant potential to arise on the skin. AK is mostly seen in Caucasians in skin areas that have extensive sun exposure throughout their lives [4]. Epidemiological data show a high occurrence rate of AK. Regions with higher ultraviolet exposure have a higher prevalence of AK. For the USA, the prevalence was estimated to range from 11 to 26%, while in Australia it ranged from 40 to 60%. In Europe, a prevalence of 15% in men and 6% in women has been documented [5]. Over the age of 70 years, 34% of men and 18% of women were found to have actinic keratotic lesions [6]. Next to fair skin type, an advanced age and lifelong sun exposure immunosuppression/-deficiency plays another important risk factor [5].Mostly, AK develops slowly and early in the disease process, they may disappear only to reappear later. Recurrence of the disease may include partial elimination of the initial lesion, subclinical lesion progression to visible status, or development of new lesions [7]. On top of this, an AK may progress to invasive SCC, the second-most common form of skin cancer [8,9]. The actual percentage of progress to invasive SCC remains unknown, and estimates vary from 5 to 20% within 10 to 25 years with reported annual transformation rates varying greatly from as low as 0.25% to as high as 16% [10]. The regression rate for a single untreated lesion is 15 to 63% after a year; recurrence rates range from 15 to 53% [11]. In general patients develop multiple AKs in one area and predicting which course each individual lesion will follow is impossible. Nonetheless, AK lesions are reliable markers for patients who are most predisposed to developing invasive SCC [4,[12][13].AK lesions typically appear in areas most frequently exposed to the sun such as the face, back of the hands, or bald scalp; 75% of lesions are found on the head, neck and forearms [14]. The lesions vary in appearance as well as size and can include erythematous scaly macules, rough pigmented patches and hyperker...

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confidence: 99%

A review of BF-200 ALA for the photodynamic treatment of mild-to-moderate actinic keratosis

Reinhold¹

2017

Future Oncol.

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“…Histological studies have shown that PDT can reverse actinic skin damage in terms of reducing epidermal expression of immunohistochemical markers of dysplasia, p53, and Ki-67 (16)(17)(18).…”

Section: Discussionmentioning

confidence: 99%

Primary Prevention of Skin Dysplasia in Renal Transplant Recipients With Photodynamic Therapy: A Randomized Controlled Trial

Togsverd‐Bo

Omland

Wulf

et al. 2015

American Journal of Transplantation

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Organ transplant recipients (OTRs) are at high risk of developing cutaneous squamous cell carcinoma (SCC); prevention includes early treatment of premalignant actinic keratosis (AK). Photodynamic therapy (PDT) is a noninvasive field therapy that reduces new AKs in patients with existing AK and delays SCC development in mice. We investigated the effect of repeated PDT over 5 years for primary prophylaxis of skin dysplasia. These data represent an interim analysis of an on-going randomized controlled trial. During 2008-2011, 25 renal transplant recipients with clinically normal skin were randomized to split-side PDT of the face, forearm and hand, the contralateral side serving as untreated control. Patients received PDT on inclusion and at 6-monthly intervals for 5 years. Blinded evaluation was performed at each visit. We found that prophylactic PDT significantly delayed onset of AK compared with untreated skin, p ¼ 0.020. At 3-year follow-up, we observed AK in 63% of patients in untreated skin areas compared with 28% of patients in PDT-treated skin, with a total number of cumulated AKs in untreated skin (n ¼ 43) compared with PDT-treated skin (n ¼ 8), p ¼ 0.005. These preliminary data indicate a novel approach to early prevention of skin dysplasia that may reduce morbidity from multiple AKs and SCCs in OTR.

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“…There are a few published reviews about photodynamic rejuvenation, most exposing the use of MAL (methyl aminolevulinic acid) or 5-ALA (5-aminolevulinic acid) as photosensitizers [46]. They reported excellent cosmetic effects, sustaining the hypothesis of induction of collagen formation in the dermal layer [44], even in the treatment of patients with severe photodamaged skin [43]. The changes in collagen and skin texture are good parameters for histological examination.…”

Section: Photomedicine -Advances In Clinical Practicementioning

confidence: 99%

“…Studies [44] have demonstrated that ROS generated after UV irradiation initiate the increase of MMPs by a complex signaling mechanism, decreasing the expression of procollagen I and procollagen-III, culminating on reduction of dermal matrix generation. Some physiological processes, such as aging and wound healing, can be evaluated relating collagen synthesis to levels of MMPs expression.…”

Section: The Role Of Matrix Metalloproteinases (Mmps)mentioning

confidence: 99%

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Low Level Energy Photodynamic Therapy for Skin Processes and Regeneration

Tedesco¹,

Jesus²

2017

Photomedicine - Advances in Clinical Practice

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Skin is the largest human organ and displays multiple functions involving structure and protection against external agents that may affect the body. Solar radiation accelerates the normal aging process and may even cause great damage leading to many different cutaneous diseases and skin cancer. Moreover, a wound in the skin may be an open channel for the access of pathogens usually exposing blood vessels for infections and causing serious complications. For many reasons, regulatory skin processes are of great deal in different approaches: basic antiaging, wound healing, and skin cancer. In a good way, photoprocesses with specific wavelength at low energy levels associated with photoactive compounds are known to cause the opposite effect, promoting the healing of cutaneous diseases and leading to well-defined outcomes in rejuvenation and antiaging. This chapter will discuss the most relevant topics in photo skin regeneration using low energy levels associated with photodynamic therapy (PDT), which emerged as a combination to potentialize molecules with the already known effects of PDT and low level laser therapy (LLLT) in the treatment of skin pathologies, known as a photobiomodulation process.

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Clinical, histopathological and immunohistochemical assessment of human skin field cancerization before and after photodynamic therapy

Cited by 122 publications

References 35 publications

A review of BF-200 ALA for the photodynamic treatment of mild-to-moderate actinic keratosis

A review of BF-200 ALA for the photodynamic treatment of mild-to-moderate actinic keratosis

Primary Prevention of Skin Dysplasia in Renal Transplant Recipients With Photodynamic Therapy: A Randomized Controlled Trial

Low Level Energy Photodynamic Therapy for Skin Processes and Regeneration

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