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

Expression of β-Catenin, E-Cadherin, and α-Smooth Muscle Actin in Basal Cell Carcinoma Before Photodynamic Therapy in Non-recurrent and Recurrent Tumors: Exploring the Ability of Predicting Photodynamic Therapy outcome

Photodynamic therapy (PDT) is an effective and cosmetically beneficial treatment of low-risk basal cell carcinomas (BCCs). To optimize PDT response, it is important to correctly select tumors. We sought to find markers that could identify such tumors beyond contributions from clinical and histological examination. Studies have shown that β-catenin, E-cadherin, and α-smooth muscle actin (SMA) expression can indicate BCC aggressiveness/BCC invasiveness. We wanted to use these markers in an explorative study to investigate whether they were differently expressed among non-recurring compared with recurring BCCs, to evaluate their ability of predicting PDT outcome. Fifty-two BCCs were stained with antibodies against β-catenin, E-cadherin, and α-SMA, and evaluated using immunoreactive score (IRS), subcellular localization, and stromal protein expression. Results showed that IRS of E-cadherin was significantly different among recurring compared with non-recurring BCCs and with area under a receiver operating characteristic curve of 0.71 (95% confidence interval: 0.56–0.86, p=0.025). Stromal β-catenin expression significantly increased among recurring BCCs. Some recurring BCCs had intense expression in the deep invading tumor edge. In conclusion, E-cadherin, and stromal and deep edge β-catenin expression were most prominent in BCCs that recurred post-PDT, suggesting they could potentially predict PDT outcome. Further studies are needed to investigate whether these results are of clinical value:publishedVersio

Is there a relationship between the stratum corneum thickness and that of the viable parts of tumour cells in basal cell carcinoma?

Basal cell carcinoma (BCC) is an invasive epithelial skin tumour. The thickness of the outermost epidermal layer of the skin, the stratum corneum (SC), influences drug uptake and penetration into tumour and may thereby affect the response of BCC to topical treatment. The aim was to investigate a possible relationship between the thickness of the SC and that of the viable part of BCC. Histopathological evaluations of the corresponding SC and viable tumour thickness measurements of individual BCCs of different subtypes were explored. A total of 53 BCCs from 46 patients were studied. The median tumour thickness was 1.7 mm (0.8–3.0 mm), with a significant difference between subtypes (� < 0.001). The SC had a median thickness of 0.3 mm (0.2–0.4 mm), with no difference between tumour subtypes (� = 0.415). Additionally, no significant association between the thickness of the SC and that of the viable part of the tumour was demonstrated (� = 0.381). In conclusion our results indicate that SC thickness is relatively constant in BCC

Comparison Between 8-Methoxypsoralen and 5-Aminolevulinic Acid in Killing T Cells of Photopheresis Patients Ex Vivo

Background and Objective Extracorporeal photopheresis (ECP), an established modality for cutaneous T‐cell lymphoma (CTCL) and graft‐versus‐host disease, involves ex vivo treatment of isolated leukocytes of a patient with the photosensitizing drug 8‐methoxypsoralen (8‐MOP) and ultraviolet‐A (UV‐A) exposure before reinfusion back to the patient. However, 8‐MOP binds to both diseased and normal cells and thus kills both types of the cells after UV‐A illumination with little selectivity. Clinically, this modality gives only partial response in the majority of treated patients. 5‐Aminolevulinic acid (5‐ALA), a precursor of the potent photosensitizer protoporphyrin IX (PpIX), has been shown to selectively induce PpIX in activated T lymphocytes (T cells) and could be an alternative for 8‐MOP. The objectives of this study were to investigate ex vivo 5‐ALA dark toxicity, 5‐ALA‐induced PpIX production, and photodynamic effect on T cells obtained from clinical ECP patients after the treatment of 5‐ALA or 8‐MOP plus a built‐in certified UV‐A source in the commercial Therakos™ Photopheresis System. Materials and Methods Flow cytometry was used to study dark cytotoxic effects of 5‐ALA on human leukocytes, to measure the production of 5‐ALA‐induced PpIX in CD25+ activated T cells from both diluted mononuclear cells and undiluted buffy coat samples of ECP patients and to compare photodynamic effects on CD4+ and CD8+ T cells with 5‐ALA/UV‐A or 8‐MOP/UV‐A. Results No dark toxicity of 5‐ALA on the leukocytes of ECP patients was seen at concentrations up to 10 mM for an incubation of up to 20 hours. 5‐ALA‐induced PpIX was produced more in CD25+ activated T cells than resting T cells in both diluted mononuclear cells and undiluted buffy coat samples, although there was a huge variation of samples from different individual patients. The CD4+ and CD8+ T cells treated with 5‐ALA/UV‐A were killed more than those treated with 8‐MOP/UV‐A. Conclusion These results suggest that 5‐ALA/UV‐A may have the potential for improving the efficacy of ECP. Lasers Surg. Med. 50:469–475, 2018

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