Long-Term Recurrence of Nonmelanoma Skin Cancer after Topical Methylaminolevulinate Photodynamic Therapy in a Dermato-Oncology Department

BACKGROUND: Most available studies on the efficacy of topical photodynamic therapy focus on short-to medium-term results. Long-term data are scarce. OBJECTIVE: To evaluate the long-term efficacy of photodynamic therapy with topical methylaminolevulinate to treat Bowen's disease and basal cell carcinoma in the clinical practice setting of a dermato-oncology department. METHODS: The study included patients diagnosed with Bowen's disease or basal cell carcinoma, and who received photodynamic therapy from 2004 to 2008. Treatment protocol and clinical follow-up were standardized. The primary endpoint was clinically observed recurrence in a previous photodynamic therapy-treated area. Descriptive and survival analyses were performed. RESULTS: A total of 31 Bowen's disease lesions and 44 superficial basal cell carcinoma were treated, with a median follow-up of 43.5 months. Recurrence was observed in 14 Bowen's disease lesions (53.8%) and in 11 superficial basal cell carcinoma (33.3%). Significantly higher estimates for recurrence rates were found in patients with Bowen's disease (p=0.0036) or those aged under 58 years (p=0.039). The risk of recurrence was higher in patients with Bowen's disease than in those with superficial basal cell carcinoma and younger patients. CONCLUSIONS: Recurrence should be considered when choosing to treat non-melanoma skin cancer with photodynamic therapy. Younger age and Bowen's disease were independent predictors for long-term recurrence, suggesting the need to establish an extended period of follow-up for this subset of patients.

Swiss clinical practice guidelines for skin cancer in organ transplant recipients.

Patients with a solid organ transplant have increased in numbers and in individual survival in Switzerland over the last decades. As a consequence of long-term immunosuppression, skin cancer in solid organ recipients (SOTRs) has been recognized as an important problem. Screening and education of potential SOTRs about prevention of sun damage and early recognition of skin cancer are important before transplantation. Once transplanted, SOTRs should be seen by a dermatologist yearly for repeat education as well as early diagnosis, prevention and treatment of skin cancer. Squamous cell carcinoma of the skin (SCC) is the most frequent cancer in the setting of long-term immunosuppression. Sun protection by behaviour, clothing and daily sun screen application is the most effective prevention. Cumulative sun damage results in field cancerisation with numerous in-situ SCC such as actinic keratosis and Bowen's disease which should be treated proactively. Invasive SCC is cured by complete surgical excision. Early removal is the best precaution against potential metastases of SCC. Reduction of immunosuppression and switch to mTOR inhibitors and potentially, mycophenolate, may reduce the incidence of further SCC. Chemoprevention with the retinoid acitretin reduces the recurrence rate of SCC. The dermatological follow-up of SOTRs should be integrated into the comprehensive post-transplant care.

NLRP3 promotes inflammation-induced skin cancer but is dispensable for asbestos-induced mesothelioma.

Asbestos exposure can result in serious and frequently lethal diseases, including malignant mesothelioma. The host sensor for asbestos-induced inflammation is the NLRP3 inflammasome and it is widely assumed that this complex is essential for asbestos-induced cancers. Here, we report that acute interleukin-1β production and recruitment of immune cells into peritoneal cavity were significantly decreased in the NLRP3-deficient mice after the administration of asbestos. However, NLRP3-deficient mice displayed a similar incidence of malignant mesothelioma and survival times as wild-type mice. Thus, early inflammatory reactions triggered by asbestos are NLRP3-dependent, but NLRP3 is not critical in the chronic development of asbestos-induced mesothelioma. Notably, in a two-stage carcinogenesis-induced papilloma model, NLRP3-deficient mice showed a resistance phenotype in two different strain backgrounds, suggesting a tumour-promoting role of NLRP3 in certain chemically-induced cancer types.

Fighting skin cancer with prodrugs

Excessive exposure to uv light initiates melanoma in the skin. Tumour-specific enzymes are hijacked to deliver anticancer drugs.

Long-term follow-up of topical 5-aminolaevulinic acid photodynamic therapy diode laser single session for non-melanoma skin cancer

Photodynamic therapy (PDT) is based on the association of a light source and tight sensitive agents in order to cause the selective death of tumor cells. To evaluate topical 5-aminolaevulinic acid (5-ALA) and diode laser photodynamic single session therapy single session for non-melanoma skin cancer (NMSC), a long-term follow-up was performed. Nineteen Bowen`s disease (BD) and 15 basal cell. carcinoma (BCC) lesions were submitted to 6-h topical and occlusive 20% 5-ALA plus DMSO and EDTA, and later were exposed to 630 nm diode laser, 100 or 300 J cm(-2) dose. At 3 months tumor-free rate was 91.2% (31/34) whereas at 60 months, 57.7% (15/26), slightly higher in BCC (63.6%; 7/11). The relation between the reduction of the clinical response and the increase of tumor dimension observed at 18 months was lost at 60 months. The sBCC recurrence was earlier compared to the nBCC one. ALA-PDT offered important advantages: it is minimally invasive, an option for patients under risk of surgical complications; clinical feasibility; treatment of multiple lesions in only one session or lesions in poor heating sites and superior esthetical results. However, the recurrence rate increase after ALA-PDT diode laser single session can be observed at tong-term follow-up, and the repetitive sessions, an additional. advantage of the method, is strongly recommended. The clinical response and recurrence time seem to be related to the laser light dose and NMSC types/sub-types, thickness and dimension, which must be considered for the choice of the ALA-PDT. (C) 2009 Elsevier B.V. All rights reserved.

Economic evaluation of skin cancer prevention in Australia

Objectives
Australia has the highest incidence of skin cancer in the world, despite prevention campaigns being implemented since the early 1980s. This study assesses the cost-effectiveness of a skin cancer prevention program (named SunSmart) since it was introduced, together with its potential cost-effectiveness as an upgraded and ongoing national program.

Methods
The reduction in melanoma incidence attributable to SunSmart was modelled as the primary end-point. Historical expenditures on SunSmart were obtained from representative Australian states in three latitude zones. Melanoma incidence rates from these states were used to model key health outcomes. Non-melanoma skin cancer was modelled separately based on national survey results.

Results
We estimate that SunSmart has averted 28,000 disability-adjusted life-years (DALYs), equivalent to 22,000 life-years saved, in the state of Victoria since its introduction in 1988, as well as saving money from cost offset in skin cancer management (dominant). An upgraded national program for the next 20 years is estimated to avert 120,000 DALYs, with associated reductions in the use of health care resources. It remains a dominant intervention in which every dollar invested in SunSmart will return an estimated AU$2.30.

Conclusions
This study demonstrates that a sustained modest investment in skin cancer control is likely to be an excellent value for money.

Economic evaluation of a skin cancer prevention program in Australia : past achievements and future prospects

Objectives
Australia has the highest incidence of skin cancer in the world. Skin cancer prevention campaigns have been implemented in Australia for over two decades. The most notable is under the brand name, SunSmart. The aim of the current study is to assess the cost-effectiveness of SunSmart in the past and the potential cost-effectiveness of an ongoing national SunSmart program with optimal investment in the future.

Methods
An economic evaluation from a health sector perspective was conducted using the reduction in skin cancer incidence attributable to the SunSmart program modelled as the primary end-point. Historical SunSmart program expenditures were obtained from three representative states in three latitude zones, covering different levels of UVR exposure. Melanoma incidence rates from the three representative state cancer registers were used to model the health outcomes. Program effectiveness was assessed by the comparison between the well-resourced SunSmart state (Victoria) and the under-invested states (New South Wales and Queensland). Non-Melanoma Skin Cancer (NMSC) was modelled based on national survey results. 2003 was chosen as the reference year and future costs/outcomes over a 20 year time horizon were discounted at 3%.
The future level of investment in a national SunSmart was chosen to strengthen current practice by increasing current investment to a realistic and achievable level. This conservative increase in investment (expressed as ‘$ per capita’) reflected the investment level that has been achieved in Victoria over sustained periods. To model the potential cost-effectiveness of an upgraded national SunSmart program, a conservative approach was taken, whereby the same magnitude of effectiveness from 1988 to 2003 was applied to future skin cancer incidence.

Results
SunSmart in Victoria has saved 22,300 life-years, averted 27,900 disability-adjusted life-years(DALYs)(discounted) since its introduction in 1988 and achieved an incremental cost-effectiveness ratio (ICER) of $AUD 680 per life-year saved (LYS) and $AUD 540 per DALY averted. When the cost-offset from the estimated reduction in skin cancer treatment costs were taken into account, SunSmart achieved ‘dominance’. The net cost of SunSmart in the past was an estimated saving of $AUD 93 million. An upgraded national SunSmart for the next 20 years would save 91,000 life-years and avert 122,000 DALYs (discounted), involving an increased investment level from the current $AUD 0.07 per capita to the historical average of $AUD 0.28 per capita. The ICER for the upgraded SunSmart program was estimated at $AUD 940 per LYS and $AUD 700 per DALY averted. When the cost-offset is included, the program achieves dominance with a cost saving of $AUD 115 million – an estimated $AUD 2.32 return for every dollar invested between 2003 and 2022.

Conclusions
This study demonstrates that a sustained modest investment in skin cancer control is likely to be excellent value-for-money. While the available data base is certainly not prefect, key parameters would have to change dramatically for this conclusion to be challenged.

A critical analysis of screening for skin cancer: participation among older males

 This thesis was a critical examination of participation in skin cancer screening for men over the age of 50 years. This research explored subjective experiences of skin cancer screening, participation in the process, perceptions of skin cancer and factors that influence men’s willingness to undergo skin cancer screening.

Prevalence of precancerous skin lesions and non-melanoma skin cancer in Japanese-Brazilians in Bauru, São Paulo State, Brazil

Manifestações cutâneas pré-neoplásicas e neoplásicas em asiáticos são infreqüentes e pouco documentadas. O Brasil possui o maior contingente de imigrantes japoneses e 70% deles residem no Estado de São Paulo. A prevalência dessas lesões em nipo-brasileiros é desconhecida. O presente estudo tem como objetivo avaliar a prevalência de queratoses actínicas e tumores cutâneos não melanomas em nipo-brasileiros acima de trinta anos de 1ª geração ou 2ª geração, sem miscigenação, residentes na cidade de Bauru, no ano de 2006. Dos 567 nipo-brasileiros submetidos a exame dermatológico, diagnosticou-se queratose actínica em 76 pacientes, com média de idade de 68,9 anos, e único carcinoma basocelular em paciente do sexo feminino de 39 anos. No Japão, a prevalência de queratose actínica é de 0,76% a 5% e a incidência de tumores cutâneos não melanomas é de 1,2 a 5,4/100 mil. Os nipo-brasileiros de Bauru apresentaram prevalência de 13,4% de queratoses actínicas e idade mais precoce de aparecimento. Proximidade com o Equador e atividades rurais contribuem para esses achados. A presença de melanose solar demonstrou risco 1,9 vez maior de desenvolver queratose actínica.

Synthesis, antioxidant and photoprotection activities of hybrid derivatives useful to prevent skin cancer

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)