Olle Larkö

Pain caused by photodynamic therapy of skin cancer

Summary Pain resulting from photodynamic therapy (PDT) of skin cancer was investigated. The study included 69 lesions (60 patients) with different types of skin tumours or precursors. Protoporphyrin IX, which is produced by the topical application of δ‐aminolevulinic acid, was used as a photosensitizing agent. Twenty‐three of the lesions (19 patients) were examined with a fluorescence imaging system which demarcates the tumour area from the healthy skin and visualizes the contrast between the fluorescence from healthy skin and that from the tumour. EMLA® is used on all patients as part of our routine PDT protocol but despite this the major side‐effect of PDT is pain during treatment. There is a large variation in pain intensity experienced by the patients, as measured by a visual analogue scale (VAS). Patients with actinic keratoses experienced more pain than those with Bowens disease or basal cell carcinoma. The mean VAS score was higher when treating lesions located on the head than when treating lesions on the torso or the extremities. Also, treatment of large skin areas resulted in more pain than treatment of small areas, and men experienced more pain than women. The pain experienced by the patients did not correlate with treatment dose, Fitzpatrick skin type, age or fluorescence intensity.

Photodynamic therapy of actinic keratosis at varying fluence rates: assessment of photobleaching, pain and primary clinical outcome

Background  Although photodynamic therapy (PDT) is becoming an important treatment method for skin lesions such as actinic keratosis (AK) and superficial basal cell carcinoma, there are still discussions about which fluence rate and light dose are preferable. Recent studies in rodents have shown that a low fluence rate is preferable due to depletion of oxygen at high fluence rates. However, these results have not yet been verified in humans.

Review of photodynamic therapy in actinic keratosis and basal cell carcinoma

The number of non-melanoma skin cancers is increasing worldwide, and so also the demand for effective treatment modalities. Topical photodynamic therapy (PDT) using aminolaevulinic acid or its methyl ester has recently become good treatment options for actinic keratosis and basal cell carcinoma; especielly when treating large areas and areas with field cancerization. The cure rates are usually good, and the cosmetic outcomes excellent. The only major side effect reported is the pain experienced by the patients during treatment. This review covers the fundamental aspects of topical PDT and its application for treatment of actinic keratosis and basal cell carcinoma. Both potentials and limitations will be reviewed, as well as some recent development within the field.

Percutaneous absorption of the sunscreen benzophenone-3 after repeated whole-body applications, with and without ultraviolet irradiation

Background  Benzophenone‐3 (BZ‐3; 2‐hydroxy‐4‐methoxybenzophenone, oxybenzone) is commonly used to absorb ultraviolet (UV) radiation. BZ‐3 penetrates the skin and can be found in the urine. The amount varies between 0·4% and 2%. This seems to be the main metabolic pathway in rats.

Important factors for pain during photodynamic therapy for actinic keratosis

Photodynamic therapy (PDT) is an efficient treatment for actinic keratosis. A common problem, however, is pain. The aim of this study was to investigate pain during PDT for actinic keratosis. The possibility of using capsaicin cream for pain relief was also assessed. Pain was investigated during aminolaevulinic acid PDT in 91 patients. Size, redness, scaling and induration of the lesions were recorded. Maximum pain during treatment was registered, using a visual analogue scale (0-10). The pain-reducing efficacy of capsaicin was tested in a pilot study in six patients (10 lesions). These patients were pre-treated with capsaicin cream for one week before commencing PDT. Pain was found to be normally distributed around a mean value of visual analogue scale 4.6. Larger lesions gave more pain (p=0.001). The redness of the actinic lesions was found to be related to PDT-induced pain (p=0.01), the reduction of actinic area (p=0.007), and the cure rate (p=0.01). The redder the actinic area, the better the treatment outcome and the more pain experienced. Patients with the largest reduction in the actinic area experienced more pain (p=0.053). The most important factors for presence of pain seem to be the size and the redness of the lesion. No significant pain relief was experienced after pre-treatment with capsaicin.

PERCUTANEOUS ABSORPTION OF BENZOPHENONE-3, A COMMON COMPONENT OF TOPICAL SUNSCREENS

Summary Benzophenone‐3 (BZ‐3) is a commonly used, chemical UV‐absorber. It has been used for many years to protect against UV‐radiation. Previous studies have shown that BZ‐3 penetrates the skin, and it can be found in urine, faeces, and blood. In this study we examined the percutaneous absorption of BZ‐3. The amount of BZ‐3 absorbed was measured in urine, as experimental studies in the rat have shown that urine is the major route of excretion. Eleven volunteers applied the recommended amount of a commercially available sunscreen and urine samples were collected during a 48‐h period after application. The average total amount excreted was 11 mg, median 9.8 mg, which is approximately 0.4% of the applied amount of BZ‐3. Some of the volunteers still excreted BZ‐3 48 h after application. It is evident that BZ‐3 undergoes conjugation in the body to make it water soluble. However, we do not know at what age the ability to conjugate is fully developed, and therefore for children physical filters such as titanium dioxide and/or zinc oxide might still be considered a more appropriate sunscreen component.

Premalignant and malignant skin lesions in renal transplant patients.

Among 129 renal transplant patients with 3–16 years of posttransplant observation time, and residents in a low ultraviolet radiation area, 25 (19.4%) had premalignant or malignant skin lesions, a 3-fold increase over a control population collected randomly. Thirteen (10.1%) had skin cancer, a 7-fold increase. Nine patients had multiple lesions; none had metastatic disease. Multiple regression analysis revealed age, outdoor occupation, and transplantation/immunosuppression to be equally significant risk factors for skin malignancy. Transplant patients should be educated and periodically examined for early detection of skin malignancies.

Treatment of superficial basal cell carcinomas using topically applied delta-aminolaevulinic acid and a filtered xenon lamp

Objective To evaluate the treatment of superficial basal cell carcinomas (SBCC) using photodynamic therapy with topically applied delta-aminolaevulinic acid (ALA) and a filtered short arc xenon lamp as a light source.Method An oil-in-water emulsion containing 20% ALA was applied topically to the lesion sites which were then occluded for 3 h. Irradiation was performed in a single session of 10 min using 125 or 166 mW/cm2 in the wavelength range (620–670 nm, giving a radiation dose of 75 or 100 J/cm2, respectively. Urine samples obtained in connection with the treatment were examined for traces of porphobilinogen and porphyrin. The therapy outcome was determined by histological examination of punch biopsies or by clinical verification. A follow-up scheduled for 5 years was initiated.Patients A group of 37 patients with histologically verified SBCCs were included. A total of 190 SBCCs were treated. Also included were six patients with 10 nodular basal cell carcinomas and five patients with 18 Mb. Bowen. The urine samples from three patients showed traces of porphyrins.Results Of the 157 SBCCs followed-up for 6 months, 144 were cleared giving a clearance rate of 92%. Of the nodular basal cell carcinomas and Mb. Bowens, 2 of ten and 11 of 18 were cleared, respectively.Conclusion Photodynamic therapy is well suited to the treatment of SBCCs giving good cosmetic results regardless of lesion size. The filtered xenon lamp proved to be particularly suitable for photodynamic therapy.

Natural UV‐B radiation received by people with outdoor, indoor, and mixed occupations and UV‐B treatment of psoriasis

Measurements have been made of the biologically‐effective environmental UV‐B radiation [UV‐B(BE)] received by people in different occupations in Sweden. These UV‐B(BE) doses have been compared with those received from artificial UV‐B radiation by patients undergoing phototherapy for psoriasis. The results indicate that for patients with outdoor occupations the therapeutic dose contributes something like one third of their total UV‐B(BE) presumably only to the hands and face. For patients who work indoors, however, the therapeutic dose can be anything from 50%to almost 100% of their total UV‐B(BE) burden.

Bispectral fluorescence imaging of aggressive basal cell carcinoma combined with histopathological mapping: a preliminary study indicating a possible adjunct to Mohs micrographic surgery

Background  Fluorescence imaging is an attractive diagnostic technique for skin tumour demarcation with potential to move to clinical use. Bispectral fluorescence imaging combines skin autofluorescence with δ‐aminolaevulinic acid‐induced fluorescence. To evaluate the technique, fluorescence data must be compared with the histopathological extent of the tumour, which is the purpose of the current study.