Gertruud A. M. Krekels

Photodynamic therapy versus topical imiquimod versus topical fluorouracil for treatment of superficial basal-cell carcinoma: a single blind, non-inferiority, randomised controlled trial

BACKGROUND Superficial basal-cell carcinoma is most commonly treated with topical non-surgical treatments, such as photodynamic therapy or topical creams. Photodynamic therapy is considered the preferable treatment, although this has not been previously tested in a randomised control trial. We assessed the effectiveness of photodynamic therapy compared with imiquimod or fluorouracil in patients with superficial basal-cell carcinoma. METHODS In this single blind, non-inferiority, randomised controlled multicentre trial, we enrolled patients with a histologically proven superficial basal-cell carcinoma at seven hospitals in the Netherlands. Patients were randomly assigned to receive treatment with methylaminolevulinate photodynamic therapy (MAL-PDT; two sessions with an interval of 1 week), imiquimod cream (once daily, five times a week for 6 weeks), or fluorouracil cream (twice daily for 4 weeks). Follow-up was at 3 and 12 months post-treatment. Data were collected by one observer who was blinded to the assigned treatment. The primary outcome was the proportion of patients free of tumour at both 3 and 12 month follow up. A pre-specified non-inferiority margin of 10% was used and modified intention-to-treat analyses were done. This trial is registered as an International Standard Randomised controlled trial (ISRCTN 79701845). FINDINGS 601 patients were randomised: 202 to receive MAL-PDT, 198 to receive imiquimod, and 201 to receive fluorouracil. A year after treatment, 52 of 196 patients treated with MAL-PDT, 31 of 189 treated with imiquimod, and 39 of 198 treated with fluorouracil had tumour residue or recurrence. The proportion of patients tumour-free at both 3 and 12 month follow-up was 72.8% (95% CI 66.8-79.4) for MAL-PDT, 83.4% (78.2-88.9) for imiquimod cream, and 80.1% (74.7-85.9) for fluorouracil cream. The difference between imiquimod and MAL-PDT was 10.6% (95% CI 1.5-19.5; p=0.021) and 7.3% (-1.9 to 16.5; p=0.120) between fluorouracil and MAL-PDT, and between fluorouracil and imiquimod was -3.3% (-11.6 to 5.0; p=0.435. For patients treated with MAL-PDT, moderate to severe pain and burning sensation were reported most often during the actual MAL-PDT session. For other local adverse reactions, local skin redness was most often reported as moderate or severe in all treatment groups. Patients treated with creams more often reported moderate to severe local swelling, erosion, crust formation, and itching of the skin than patients treated with MAL-PDT. In the MAL-PDT group no serious adverse events were reported. One patient treated with imiquimod and two patients treated with fluorouracil developed a local wound infection and needed additional treatment in the outpatient setting. INTERPRETATION Topical fluorouracil was non-inferior and imiquimod was superior to MAL-PDT for treatment of superficial basal-cell carcinoma. On the basis of these findings, imiquimod can be considered the preferred treatment, but all aspects affecting treatment choice should be weighted to select the best treatment for patients. FUNDING Grant of the Netherlands Organization for Scientific Research ZONMW (08-82310-98-08626).

Congenital naevi treated with erbium:YAG laser (Derma K) resurfacing in neonates: clinical results and review of the literature

Background  Giant congenital melanocytic naevi (CMN) are often disfiguring, potentially malignant pigmented lesions present at birth. Their management is based on two main considerations: attempt to minimize the risk of malignancy and to obtain an acceptable cosmetic result. In the past various approaches have been used to treat these naevi.

Impact of Melanoma on Patients' Lives Among 562 Survivors: A Dutch Population-Based Study

OBJECTIVE To assess the impact of melanoma on the health-related quality of life of patients from the general population up to 10 years after diagnosis and its determinants. DESIGN A cross-sectional Dutch population-based postal survey among patients with melanoma for the years 1998 to 2008 using the Eindhoven Cancer Registry. MAIN OUTCOME MEASURES The 36-Item Short-Form Health Survey (SF-36), Impact of Cancer (IOC) questionnaire and specific melanoma-related questions. The SF-36 scores of the cases were compared with normative data. Multiple linear regression models were used to identify associated factors of SF-36 and IOC scores. RESULTS The response rate was 80%. The mean age of the 562 respondents was 57.3 years; 62% were female, and 76% had a melanoma with a Breslow thickness of less than 2 mm. The SF-36 component scores of patients with melanoma were similar to those of the normative population. In a multiple linear regression model, stage at diagnosis, female sex, age, and comorbidity were significantly associated (P<.05) with the physical and mental component scores. Women were significantly more likely to report higher levels of both positive and negative IOC. Time since diagnosis, tumor stage, and comorbidity were significant predictors of negative IOC scores. Women seemed to adjust their sun behavior more often (54% vs 67%; P<.001) than men and were more worried about the deleterious effects of UV radiation (45% vs 66%; P<.001). CONCLUSION The impact of melanoma seems to be specific and more substantial in women, suggesting that they may need additional care to cope with their melanoma optimally.

Treatment of basal cell carcinomas in patients with nevoid basal cell carcinoma syndrome

Background  Nevoid basal cell carcinoma syndrome (NBCCS) is characterized by the development of multiple basal cell carcinomas (BCCs). A major problem for these patients is the enormous amount of BCCs which can invade in the deep underlying structures, especially in the face. Different treatment modalities are used in these patients; surgical excision, Mohs micrographic surgery, cryotherapy, photodynamic therapy, ablative laser therapy and topical 5% imiquimod. There is no evidence based advice how to treat a NBCCS patient.

Botulinum toxin type A as an adjuvant treatment modality for extensive Hailey–Hailey disease

Background: Extensive Hailey–Hailey disease is often resistant to conventional topical and systemic therapies. The systemic and ablative therapies have many side effects and/or high recurrence rates. Therefore, an alternative safe and effective treatment is needed. Objective: To assess the effectiveness of botulinum toxin type A in the treatment of extensive Hailey–Hailey disease. Methods: The cases of six patients with extensive Hailey–Hailey disease resistant to multiple therapeutic regimens were studied and described. Adjuvant therapy with botulinum toxin type A/Dysport® was started in all six cases. Results: Marked improvement of the lesions was achieved with few side effects in all patients. Conclusion: Botulinum toxin type A is a safe and effective adjuvant treatment for extensive Hailey–Hailey disease.

Need for a New Skin Cancer Management Strategy

The worldwide incidence of skin cancer (especially nonmelanoma skin cancer) has increased markedly during the last decades. Skin cancer should be considered a chronic disease. To manage the future costs and quality of care for patients with skin cancer, a revised health strategy is needed. These new strategies should be combined into a disease management system that organizes health care for one well-documented health care problem using a systematic approach. This article explores multiple opportunities for the development of a disease management system regarding skin cancer that will provide structured and multidisciplinary care.

Workflow for Healthcare: A Methodology for Realizing Flexible Medical Treatment Processes

While workflow management technology is applied in many industrial domains to improve the operational efficiency of business process execution, its usage in the healthcare domain is limited. One possible cause is that healthcare processes are often considered to be more whimsical and less predictable than procedures found in industry. Extending previous work on workflow and flexibility patterns, this paper presents a methodology for realizing processes that possess the required degree of flexibility that makes them suitable for the healthcare domain. To demonstrate the methodology’s feasibility, it is applied to the processes that are found in a Dutch outpatient clinic. Interestingly, the flexibility demands of the investigated processes match quite well with the capabilities of current workflow management technologies, further motivating their increased usage in the healthcare domain.

Internet-Based Computer Tailored Feedback on Sunscreen Use

Background Skin cancer incidence rates signify the need for effective programs for the prevention of skin cancer and for helping skin cancer patients. Internet and computer tailored (CT) technology fosters the development of highly individualized health communication messages. Yet, reactions to Internet CT programs may differ per level of involvement and education level and remain understudied. Objective First, we identified perceptions concerning sunscreen use in Dutch adults and assessed differences in differences between the general public and skin cancer patients, and between low and high educated respondents. Second, we assessed program evaluations of these groups about a new Dutch CT Internet-based program promoting sunscreen use, and potential differences between groups Methods A cross-sectional research design was used. In total, 387 respondents participated and filled out an online questionnaire based on the I-Change Model assessing socio-demographics, history of skin cancer, sunscreen use, and beliefs about sunscreen use. The responses were fed into a computer program that generated personal tailored feedback on screen; next we assessed their program evaluations Results Of the 132 patients, 92 were female (69.7%) and 40 were male (30.3%). In the general population (N = 225), 139 (54.5%) respondents were female and 116 (45.5%) were male. Men (50.9 years) were 8 years older than women (43.1 years). Most patients were diagnosed with basal cell carcinoma (N = 65; 49.2%), followed by melanoma (N = 28; 21.2%) and squamous cell carcinoma (N = 10; 7.6%); 22% (N = 29) did not remember their skin cancer type. Patients had higher knowledge levels, felt significantly more at risk, were more convinced of the pros of sunscreen, experienced more social support to use sunscreen, had higher self-efficacy, and made more plans to use sunscreen than respondents without skin cancer (N=255; all P’s< .01). Low (N=196) educated respondents scored lower on knowledge (P<.003) but made more action plans (P<.03) than higher educated respondents (N=191). The CT feedback was evaluated positively by all respondents, and scored a 7.8 on a 10 point scale. Yet, patients evaluated the CT program slightly more (P<.05) positive (8.1) than non-patients. (7.6). Lower educated respondents were significantly (P<.05) more positive about the advantages of the program. Conclusions First, involvement with skin cancer was reflected in more positive beliefs toward sunscreen use in patients in comparison with non-patients. Second, the CT Internet program was well accepted by both patients and non-patients, and low and high educated respondents, perhaps because higher educated respondents were more knowledgeable about sunscreen use and skin cancer. Third, a pro-active approach as conducted in our study is very well suited to reach various groups of people and is more likely to be successful than a reactive approach

Imiquimod 5% cream as pretreatment of Mohs micrographic surgery for nodular basal cell carcinoma in the face: A prospective randomized controlled study

Background  Imiquimod 5% cream can reduce or clear superficial and small nodular basal cell carcinoma (BCC). It could be used as a pretreatment of Mohs micrographic surgery (MMS) to decrease defect size.

The incidence of skin cancer in dermatology

It is known that the incidence of skin cancer is rising rapidly worldwide, but no reliable figures on multiple nonmelanoma skin cancer (NMSC) are available.