Eidi Christensen

Photodynamic therapy with methyl aminolevulinate for prevention of new skin lesions in transplant recipients: a randomized study.

Background. Organ transplant recipients on long-term immunosuppressive therapy are at increased risk of non-melanoma skin lesions. Repeated field photodynamic therapy using topical methyl aminolevulinate (MAL) may have potential as a preventive treatment. Methods. This open randomized, intrapatient, comparative, multicenter study included 81 transplant recipients with 889 lesions (90% actinic keratoses (AK)]. In each patient, the study treatment was initially administered to one 50 cm2 area on the face, scalp, neck, trunk, or extremities (n=476 lesions) twice (1 week apart), with additional single treatments at 3, 9, and 15 months. On each occasion, the area was debrided gently and MAL cream (160 mg/g) applied for 3 hr, before illumination with noncoherent red light (630 nm, 37 J/cm2). The control, 50 cm2 area (n=413 lesions) received lesion-specific treatment (83% cryotherapy) at baseline and 3, 9, and 15 months. Additionally, all visible lesions were given lesion-specific treatment 21 and 27 months in both treatment and control areas. Results. At 3 months, MAL photodynamic therapy significantly reduced the occurrence of new lesions (65 vs. 103 lesions in the control area; P=0.01), mainly AK (46% reduction; 43 vs. 80; P=0.006). This effect was not significant at 27 months (253 vs. 312; P=0.06). Hypopigmentation, as assessed by the investigator, was less evident in the treatment than control areas (16% vs. 51% of patients; P<0.001) at 27 months. Conclusion. Our results suggest that repeated field photodynamic therapy using topical MAL may prevent new AK in transplant recipients although further studies are needed.

Guidelines for practical use of MAL-PDT in non-melanoma skin cancer.

Methyl aminolaevulinate photodynamic therapy is increasingly practiced in the treatment of actinic keratoses, Bowen’s disease and basal cell carcinomas. This method is particularly suitable for treating multiple lesions, field cancerization and lesions in areas where a good cosmetic outcome is of importance. Good treatment routines will contribute to a favourable result. The Norwegian photodynamic therapy (PDT) group consists of medical specialists with long and extensive PDT experience. With support in the literature, this group presents guidelines for the practical use of topical PDT in non‐melanoma skin cancer.

High and sustained efficacy after two sessions of topical 5-aminolaevulinic acid photodynamic therapy for basal cell carcinoma: a prospective, clinical and histological 10-year follow-up study

Background  Prolonged follow‐up data on topical photodynamic therapy (PDT) in basal cell carcinoma (BCC) are necessary for a full evaluation of its effect and for comparison with conventional treatment methods.

Photodynamic therapy with 5-aminolaevulinic acid, dimethylsulfoxide and curettage in basal cell carcinoma : a 6-year clinical and histological follow-up.

Background  Long‐term follow‐up data are needed to evaluate treatment effect after photodynamic therapy (PDT).

Cytological diagnosis of basal cell carcinoma and actinic keratosis, using Papanicolaou and May–Grünwald–Giemsa stained cutaneous tissue smear

Objective:  Cytology may become the diagnostic method of choice with the advent of new non‐invasive treatments for non‐melanoma skin cancer, as the sampling technique for cytology entails little tissue disfiguration. The aim of this study was to compare and evaluate the diagnostic performance of scrape cytology using two different cytological staining techniques, and to evaluate additional touch imprint cytology, with that of histopathology of basal cell carcinoma (BCC) and actinic keratosis (AK).

Pre-Treatment Deep Curettage Can Significantly Reduce Tumour Thickness in Thick Basal Cell Carcinoma While Maintaining a Favourable Cosmetic Outcome When Used in Combination with Topical Photodynamic Therapy

Topical photodynamic therapy (PDT) has limitations in the treatment of thick skin tumours. The aim of the study was to evaluate the effect of pre-PDT deep curettage on tumour thickness in thick (≥2 mm) basal cell carcinoma (BCC). Additionally, 3-month treatment outcome and change of tumour thickness from diagnosis to treatment were investigated. At diagnosis, mean tumour thickness was 2.3 mm (range 2.0–4.0). Pre- and post-curettage biopsies were taken from each tumour prior to PDT. Of 32 verified BCCs, tumour thickness was reduced by 50% after deep curettage (P ≤ 0.001). Mean tumour thickness was also reduced from diagnosis to treatment. At 3-month followup, complete tumour response was found in 93% and the cosmetic outcome was rated excellent or good in 100% of cases. In conclusion, deep curettage significantly reduces BCC thickness and may with topical PDT provide a favourable clinical and cosmetic short-term outcome.

Modification of extracorporeal photopheresis technology with porphyrin precursors. Comparison between 8-methoxypsoralen and hexaminolevulinate in killing human T-cell lymphoma cell lines in vitro.

BACKGROUND Extracorporeal photopheresis that exposes isolated white blood cells to 8-methoxypsoralen (8-MOP) and ultraviolet-A (UV-A) light is used for the management of cutaneous T-cell lymphoma and graft-versus-host disease. 8-MOP binds to DNA of both tumor and normal cells, thus increasing the risk of carcinogenesis of normal cells; and also kills both tumor and normal cells with no selectivity after UV-A irradiation. Hexaminolevulinate (HAL)-induced protoporphyrin-IX is a potent photosensitizer that localizes at membranous structures outside of the nucleus of a cell. HAL-mediated photodynamic therapy selectively destroys activated/transformed lymphocytes and induces systemic anti-tumor immunity. The aim of the present study was to explore the possibility of using HAL instead of 8-MOP to kill cells after UV-A exposure. METHODS Human T-cell lymphoma Jurkat and Karpas 299 cell lines were used to evaluate cell photoinactivation after 8-MOP and/or HAL plus UV-A light with cell proliferation and long term survival assays. The mode of cell death was also analyzed by fluorescence microscopy. RESULTS Cell proliferation was decreased by HAL/UV-A, 8-MOP/UV-A or HAL/8-MOP/UV-A. At sufficient doses, the cells were killed by all the regimens; however, the mode of cell death was dependent on the treatment conditions. 8-MOP/UV-A produced apoptotic death exclusively; whereas both apoptosis and necrosis were induced by HAL/UV-A. CONCLUSION 8-MOP can be replaced by HAL to inactivate the Jurkat and Karpas 299 T-cell lymphoma cells after UV-A irradiation via apoptosis and necrosis. This finding may have an impact on improved efficacy of photopheresis.

Pre-treatment Evaluation of Basal Cell Carcinoma for Photodynamic Therapy: Comparative Measurement of Tumour Thickness in Punch Biopsy and Excision Specimens

Tumour thickness affects the outcome of photodynamic therapy in basal cell carcinoma (BCC). The aim of this study was to evaluate whether punch biopsy provides reliable information on BCC tumour thickness, by comparing corresponding measurements in biopsy and excision specimens for 48 lesions in 43 patients. BCC tumours were between 0.2 and 6.1 mm thick. The mean depth of the excisions were 0.14 mm greater than that of the biopsies. Bland-Altman 95% limits of agreement were (-1.3, 1.6) mm, but the difference between measurements increased with tumour thickness. A punch biopsy tumour thickness of 1.0 mm yielded an upper 95% predicted limit for excision depth within 2.0 mm. In conclusion, there was reasonable overall agreement between corresponding measurements. A biopsy thickness of 1.0 mm suggests that the tumour will most likely be within the current accepted limits for photodynamic therapy. With increasing tumour thickness, however, individual tumour measurements may differ considerably.

Comparison of clinical and histopathological evaluations of basal cell carcinoma thickness

DEAR EDITOR, Basal cell carcinoma (BCC) can be classified into a number of different clinical and histopathological types. The clinical diagnosis is not always consistent with the histopathological diagnosis because BCC does not have a definite clinical appearance in all cases. Accordingly, the extent of tumour infiltration may not be easily measurable as it can have subclinical extensions and deep irregular delineation against normal tissue. This may have implications for treatment, as tumour thickness is regarded as an important predictor of response to minimally invasive topical therapies. Therefore, the clinician needs reliable information on BCC thickness to identify those tumours most likely to respond. At present, biopsy to provide a sample for histopathological evaluation of the tumour thickness is considered the ‘gold standard’. Even so, BCC is treated in many cases without histopathological investigation of its thickness. We report on the comparison of corresponding clinical and histopathological measurements of BCC thickness to evaluate whether the clinical assessment of tumour thickness is accurate. In addition, we evaluated the agreement between these measurements in different BCC subtypes. This prospective study was approved by the regional committee for medical research ethics and performed at the outpatient clinic at the Department of Dermatology, St. Olavs University Hospital, Trondheim, Norway. Part of the study sample was included in a previous report that compared measurements of BCC thickness from punch biopsy and excision specimens. Consecutive patients ˃ 18 years old, neither pregnant nor breast feeding, with primary histopathologically verified BCC gave written informed consent before study entry. To ensure sufficient material for both punch and excision biopsy, only lesions ≥ 9 mm were included. Two consultants and an experienced registrar in dermatology performed the clinical examinations of 12, 17 and 24 tumours, respectively. Tumour size was defined clinically as the mean value of its extreme length and width. Tumour thickness was obtained by clinical and histopathological investigations. First, the clinical thickness (in mm) was estimated by inspection and palpation of the tumour. Second, a 3-mm disposable biopsy punch (Kai Industries Co. Ltd, Gifu, Japan) was used to obtain a small tissue sample. Third, and on the same day, an elliptical resection of the whole tumour was made. Details of the processing of tumour specimens have been described previously. A single hospital pathologist measured the BCC thickness from below the stratum corneum to the bottom of the tumour nest on haematoxylin, eosin and saffron-stained slides using an ocular micrometre to a precision of 0 1 mm. The greatest measurement from each punch biopsy specimen was defined as the punch tumour thickness. The greatest measurement from the corresponding punch biopsy and excision specimens of each tumour was defined as the ‘maximum tumour thickness’ (MTT), since the thickest part could reside within either specimen. The tumours were subclassified histopathologically into three categories: superficial, nodular or aggressive (morpheaform, infiltrative, basosquamous) growth types. IBM SPSS Statistics (v.21; IBM Corp., Armonk, NY, U.S.A.) was used, and the data were normally distributed. Possible relationships between the differences and mean thickness measurements were analysed by Bland–Altman plots with a regression approach for nonuniform differences. Simple regression analyses were used to calculate the slope of the regression line between the means and differences and the SD of the residuals (res-SD). The 95% limits of agreement were then calculated as 1 96 9 res-SD with respect to the regression line. P < 0 05 was considered statistically significant. In total, 159 tumour thickness measurements from 53 BCCs of 46 patients (18 women, mean age 71 years and 28 men, mean age 73 years) were included. Tumours were located to: head/neck (n = 20), trunk (n = 27) and extremities (n = 6) with a mean size of 18 mm (range 10–30). Histopathologically, 14were superficial, 24 nodular and 15 of aggressive growth types. The mean (SD) thickness values by the clinical, punch biopsy and MTT evaluations were 1 5 (0 9), 1 7 (1 3) and 2 0 mm (1 5), respectively. The largest mean difference (0 5 mm) was found between clinical and MTT values. Figure 1 shows the Bland–Altman plot with 95% limits of agreement for the difference between the MTT and the clinical thickness. The slope of the regression line was significant (slope 0 49, P < 0 001). The 95% limits of agreement were 1 3 mm (res-SD 0 67). Figure 2 shows the Bland–Altman plot between the punch biopsy thickness and the clinical thickness. The slope of the regression line was significant (slope 0 34, P = 0 004). The 95% limits of agreement were 1 6 mm (res-SD = 0 81). As the regression lines show, there was a systematic relationship between differences and tumour thicknesses. For tumours of approximately 1 6 mm thickness, the clinical and histological results agreed. Thinner BCCs were evaluated as thicker by clinical evaluation than by the corresponding histological examination, whereas the relationship was the opposite for thicker tumours. The scatter plots (Figs 1 and 2) also present the values of thickness for different BCC subtypes. By

Spotlighting the role of photodynamic therapy in cutaneous malignancy: an update and expansion.

I read the recent review paper by Ross and colleagues with great interest. It is of great value for clinicians to have an update on the recent literature regarding the use of topical photodynamic therapy (PDT) for nonmelanoma skin cancer to offer patients the best possible treatment. The authors have raised concerns over the use of PDT for nodular basal cell carcinoma (BCC) that is more than 1 mm thick. This seems to be based on results of studies in which PDT was used as monotherapy or in combination with limited preparation of the tumor before therapy.