Intralesional photodynamic therapy induces apoptosis in basal cell carcinoma and Bowen's disease through caspase 3 and granzyme B.

BACKGROUND: Photodynamic therapy (PDT) is used to treat cutaneous cancers. It may induce cell death through direct and indirect means, including apoptosis, inflammation and certain immune mechanisms, with the depth of penetration as a potential modifying factor. OBJECTIVES: To examine the pathways of apoptosis in the intralesional PDT of basal cell carcinoma (BCC) and intraepidermal squamous cell carcinoma (Bowen's disease). METHODS: Sixteen patients with superficial or nodular BCC and Bowen's disease were treated with intralesional aminolevulinic acid-PDT. Biopsies were taken at baseline and 24 h post-PDT, and sections were examined by immunohistochemistry for the expression of markers of apoptosis, such as caspase 3, involved in the intrinsic apoptotic pathway, granzyme B, a caspase-independent apoptotic mediator, and the proapoptotic markers BAX and BAK. RESULTS: Apoptotic cells stained with TUNEL showed statistically significant staining at 24 h post PDT (p < 0.01 in both BCC and Bowen's lesions). Caspase 3 (p < 0.01 in BCC and p < 0.05 in Bowen's) and granzyme B (p < 0.01 in BCC and p < 0.01 in Bowen's) were significantly increased at 24 h post-PDT. BAX expression was apparently increased compared to baseline in Bowen's lesions at 24 h post-PDT, whereas Bak was upregulated both in BCC and Bowen's disease at baseline and at 24 h post-PDT. CONCLUSION: Intralesional PDT induces apoptosis in BCC and Bowen's disease via common and alternative apoptotic pathways involving granzyme B. Proapoptotic factors Bak in both BCC and Bowen and Bax in Bowen's disease appear to increase by intralesional PDT at 24 h.

Conventional vs. daylight photodynamic therapy for patients with actinic keratosis on face and scalp: 12-month follow-up results of a randomized, intra-individual comparative analysis.

INTRODUCTION: Daylight PDT (DLPDT) is a new PDT procedure. Several trials demonstrate that DLPDT achieves similar response rates with conventional PDT (CPDT) in the treatment of non-hyperkeratotic actinic keratoses (AKs) in a nearly painless way. It seems that DLPDT represents a more convenient and equally effective treatment modality. Data on long-term efficacy of DLPDT are limited. OBJECTIVE: To compare short- and long-term efficacy, safety and tolerability of DLPDT with that of CPDT in face and scalp AKs. METHODS: The study, an intra-individual right-left comparison study, was conducted in three centres in North, Center and South Greece. Eligible patients received either DLPDT or CPDT randomly allocated to alternate sides of face or scalp. Patients were evaluated at baseline, 3 and 12 months after treatment. Assessments included lesion response at 3 and 12 months, PDT-associated pain during PDT session, local skin reactions 3 days after treatment as well as patients' preference 3 months after treatment. RESULTS: A total of 46 patients completed the study. Three months after treatment, the overall lesion complete response rate was 78% for DLPDT and 80.6% for CPDT. At the 12-month follow-up, response rate decreased to 71.8% and 73.7% for DLPDT and CPDT accordingly. Regarding response based on lesion grade, response rates obtained in grade-I lesions were higher with DLPDT, while treatment with CPDT resulted to higher rates of cured grade-II lesions at both follow-up visits. Results were not supported by statistical significance. DLPDT was associated with significantly lower pain and reduced severity of local skin reactions. Patients' preference favoured DLPDT. CONCLUSIONS: Our study demonstrated that DLPDT is similar to CPDT in terms of long-term efficacy and recurrence rates in the treatment of face and scalp AKs. DLPDT demonstrated a better tolerability profile as it was associated with lower pain and less severe adverse events.

Applicability of dermoscopy for evaluation of patients' response to nonablative therapies for the treatment of superficial basal cell carcinoma.

BACKGROUND: Applicability of dermoscopy in evaluation of outcome and monitoring of superficial basal cell carcinoma (sBCC) after nonablative therapies has not been sufficiently assessed. OBJECTIVES: Certain dermoscopic criteria, namely pigmented structures, ulceration and arborizing vessels, have been suggested to predict the presence of residual disease [residual disease-associated dermoscopic criteria (RDADC)]. We aimed to assess this hypothesis. PATIENTS AND METHODS: Lesions exhibiting RDADC 3 months after treatment were biopsied and in the case of histopathological confirmation were excised. Lesions characterized by white/red structureless areas, superficial fine telangiectasias, or lacking any dermoscopic criterion, were monitored for 12 months. RESULTS: At the 3-month evaluation, one or more of the RDADC were detected in 25/98 (25·5%) sBCCs, in which histology confirmed tumour persistence. In 45 (61·6%) of the 73 remaining lesions, dermoscopy showed white/red structureless areas and/or superficial fine telangiectasias. Twenty-eight lacked any dermoscopic criterion of sBCC. The two latter groups entered follow-up. In total, disease recurred in 13 (17·8%) of the 73 lesions. CONCLUSIONS: RDADC accurately predict residual disease. Absence of dermoscopic criteria of sBCC safely predicts complete histopathological clearance. Detection of white/red structureless areas and/or superficial fine telangiectasias warrants close monitoring to recognize early recurrence.

Topical photodynamic therapy significantly reduces epidermal Langerhans cells during clinical treatment of basal cell carcinoma.

BACKGROUND: Topical photodynamic therapy (PDT) is a widely applied treatment for basal cell carcinoma (BCC). PDT-induced immunosuppression leading to reduced antitumour immune responses may be a factor in treatment failure. OBJECTIVES: To examine the impact of topical PDT on leucocyte trafficking following clinical treatment of BCC. METHODS: Superficial BCCs in eight white caucasian patients were treated with methyl aminolaevulinate (MAL)-PDT. Biopsies for immunohistochemical assessment were taken from BCCs pre-PDT, 1 h and 24 h post-PDT and from untreated healthy skin. RESULTS: Treatment of BCC with MAL-PDT produced a rapid neutrophil infiltration, commencing by 1 h and significantly increased at 24 h post-PDT (P < 0·05 compared with baseline). An associated increase in the number of blood vessels expressing E-selectin was observed at 1 h and 24 h post-PDT (both P < 0·05 compared with baseline). In contrast, the number of epidermal Langerhans cells fell sharply by 1 h post-PDT, and remained significantly reduced at 24 h post-PDT (both P < 0·05 compared with baseline). CONCLUSIONS: Reduction of Langerhans cells during clinical treatment of BCC might potentially impact negatively on antitumour responses through reduced activation of tumour-specific effector cells. Investigation of modified PDT protocols with the aim to minimize immunosuppressive effects while maintaining antitumour efficacy is warranted.

Topical aminolaevulinic acid-photodynamic therapy produces an inflammatory infiltrate but reduces Langerhans cells in healthy human skin in vivo.

BACKGROUND: Topical photodynamic therapy (PDT) elicits a therapeutic response in both skin cancer and immune-mediated skin disorders. While PDT induces direct cell death, host inflammatory and immune responses to PDT may contribute to the therapeutic effects. OBJECTIVES: To examine the impact of topical PDT on leucocyte trafficking and mediators of chemotaxis in healthy human skin. METHODS: Aminolaevulinic acid (ALA)-PDT was performed on the buttock skin of seven healthy volunteers. Biopsies for immunohistochemical assessment were taken 1, 4 and 24 h post-PDT and from untreated contralateral buttock skin (baseline). RESULTS: A significant dermal neutrophilic infiltrate appeared early, peaking at 4 h (P < 0·01) and returning to near baseline by 24 h. Expression of E-selectin was significantly higher at 4 h (P < 0·05) and correlated strongly with neutrophil numbers (r = 0·93). Expression of intercellular adhesion molecule 1 was significantly elevated after 24 h (P < 0·05) with an apparent gradual increase in CD4+ T cells up to this time point. Notably, epidermal Langerhans cells were significantly reduced 24 h post-PDT compared with baseline (P < 0·01) and comprised a significantly larger proportion of cells with migratory rather than dendritic morphology (P < 0·05). The number of epidermal cells expressing tumour necrosis factor-α significantly increased at 4 h (P < 0·05) and remained elevated 24 h post-PDT, whereas no significant change in expression of interleukin (IL)-1ß or IL-8 was seen. CONCLUSIONS: Reduction of Langerhans cells by topical PDT of human skin may play a significant role in PDT-induced local immunosuppression, potentially benefiting the treatment of immune-mediated skin disorders but negatively impacting on antitumour responses. Further exploration according to disease indication/treatment protocol is warranted.

The effect of methylprednisolone on the sodium and water content of the dog lung after hemorrhagic shock.

Out of 17 mongrel dogs, 3 were subjected on one and two hours of hemorrhagic shock, while the remaining four served as controls. In five of the thirteen dogs, 30 mg/kg of methylprednisolone sodium succinate were administered intravenously one hour after hemorrhage. All animals were sacrificed at the end of the experiment, their lungs were removed and the sodium and water content was measured. The sodium content was found to be markedly increased at the end of two hours of hemorrhagic shock. This increase was prevented significantly by the administration of pharmacological doses of methylprednisolone given at one hour of hemorrhagic shock. No significant change in total lung water was noted, even after two hours of hemorrhagic shock. The results of this study suggest that early intravenous administration of large doses of methylprednisolone may be beneficial to patients in protracted hemorrhagic shock, who are at high risk of developing pulmonary complications.