Recurrence rates of cutaneous squamous cell carcinoma of the head and neck after Mohs micrographic surgery vs. standard excision: a retrospective cohort study.

BACKGROUND: Recurrent cutaneous squamous cell carcinoma (cSCC) has been associated with an increased risk of local functional and aesthetic comorbidity, metastasis and mortality. OBJECTIVES: To compare the risk of recurrence between Mohs micrographic surgery (MMS) and standard excision for cSCC of the head and neck. METHODS: This was a retrospective cohort study of all patients with a cSCC treated with MMS or standard excision at the departments of dermatology of a secondary or tertiary care hospital in the Netherlands between 2003 and 2012. To detect all recurrences, patients were linked to the Dutch pathology registry. To compare the risk of recurrence between MMS and standard excision, hazard ratios (HRs) were used adjusted for clinical tumour size > 2 cm and deep tumour invasion. RESULTS: A total of 579 patients with 672 cSCCs were included: 380 cSCCs were treated with MMS and 292 with standard excision. The risk of recurrence was 8% (22 of 292) after standard excision during a median follow-up of 5·7 years [interquartile range (IQR) 3·5-7·8], which was higher than the 3% (12 of 380) after MMS during a median follow-up of 4·9 years (IQR 2·3-6·0). The cumulative incidence of recurrence was higher for standard excision than for MMS during the entire follow-up period of 8·6 years. Carcinomas treated with MMS were at a three times lower risk of recurrence than those treated with standard excision when adjusted for tumour size and deep tumour invasion (adjusted HR 0·31, 95% confidence interval 0·12-0·66). CONCLUSIONS: MMS might be superior to standard excision for cSCCs of the head and neck because of a lower rate of recurrence.

Reliability of diagnosis from Mohs slides: interpersonal and intrapersonal agreement on basal cell carcinoma presence and histological subtype.

BACKGROUND: The success of Mohs micrographic surgery (MMS) depends partly on the correct diagnosis of slides. OBJECTIVES: To determine reliability of diagnosis from Mohs slides. METHODS: This was a prospective study evaluating the reliability of diagnosis from Mohs slides of basal cell carcinoma (BCC) presence, BCC location on the slide and BCC subtype among six raters who independently assessed 50 Mohs slides twice with a 2-month interval. Slides were randomly selected whereby difficult-to-diagnose slides were oversampled. For each slide, a reference diagnosis was established by an expert panel. Cohen's kappa (κ) was calculated to determine levels of agreement interpersonally (rater vs. reference diagnosis) and intrapersonally (rater at T1 vs. T2). Multivariable logistic regression was used to determine independent risk factors for slides with interpersonal discordant diagnosis. The variables studied were BCC presence, whether a slide was scored as easy or difficult to diagnose, review duration of the 50 slides, profession and years of experience in diagnosis from Mohs slides. RESULTS: Interpersonal and intrapersonal agreement were substantial on BCC presence (κ = 0·66 and 0·68) and moderate on BCC subtype (κ = 0·45 and 0·55). Slides that were scored as difficult to diagnose were an independent risk factor for interpersonal discordant diagnosis on BCC presence (odds ratio 3·54, 95% confidence interval 1·81-6·84). CONCLUSIONS: Reliability of diagnosis from Mohs slides was substantial on BCC presence and moderate on BCC subtype. For slides that are scored difficult to diagnose, a second opinion is recommended to prevent misinterpretation and thereby recurrence of skin cancer.

Optimizing ALA-PDT in the management of non-melanoma skin cancer by fractionated illumination.

The aim of this review was to describe briefly the mechanism and history of photodynamic therapy (PDT). The achieved preclinical and clinical results in Rotterdam are discussed in the light of a search to optimize aminolevulinic acid-photodynamic therapy (ALA-PDT). As the incidence of skin cancer is rising, an optimized treatment in non-melanoma skin cancer is needed.

Liposomes in dermatology today.

Liposomes are vesicles consisting of spherical phospholipid bi-layers with specific properties making them useful for topical application of drugs. Liposome research has expanded considerably over the last 30 years and nowadays, it is possible to construct a wide range of liposomes varying in size, phospholipids composition and surface characteristics to suit the specific application for which they are intended. In dermatology, the topical application of liposomes has proven to be of therapeutic value. Liposomes can be used as carriers for hydrophilic as well as lipophilic therapeutic agents because of their amphipathic character. They may improve stabilization of instable drugs by encapsulating them and serve as penetration enhancers facilitating the transport of compounds that otherwise cannot penetrate the skin. Liposomes help in reducing skin irritation by sustaining the release of drugs and by hydration of the epidermis. They also have the potential to target drugs into the pilosebaceous structures and hence they have an additional advantage for treatment of hair follicle-associated disorders. Clinical data indicate that 5-ALA encapsulated in liposomes improves the quality of Fluorescence Diagnosis by ALA-induced Porphyrins (FD) and optimizes the results of Photodynamic Therapy (PDT).

Fractionated aminolevulinic acid-photodynamic therapy provides additional evidence for the use of PDT for non-melanoma skin cancer.

BACKGROUND: Photodynamic therapy (PDT) is an accepted treatment for superficial basal cel carcinoma (sBCC) and Bowens disease. In Rotterdam, extensive preclinical research has lead to an optimized twofold illumination scheme for aminolevulinic acid-PDT (ALA-PDT). OBJECTIVE: To provide additional evidence of ALA-PDT for sBCC, Bowens disease (BD), nodular BCC (nBCC) and actinic keratosis (AK) using a 2-fold illumination scheme after a single application of ALA. METHODS: Five hundred fifty-two lesions (430 sBCC, 20 nBCC, 32 BD, 70 AK) were treated with ALA-PDT using a twofold illumination scheme. ALA was applied topically for 4 h. Lesions were treated with two light fractions of 20 and 80 J/cm(2) separated by a 2-h dark interval. RESULTS: After a minimum follow-up of 12 months, in average follow-up of 2 years, an overall complete response of 95% was seen for all lesions. For sBCC, the complete response at 2 years was 97% (for AK 98%, for BD 84% and for nBCC 80% after 2 years). A sub-analysis of the results of lesions larger than 2 cm showed CR at 2 years of 89% for all lesions (n = 57). Cosmetic outcome was good to excellent in 95% of the treated lesions. CONCLUSION: ALA-PDT using a twofold illumination scheme of 20 plus 80 J/cm(2) separated by a 2-h dark interval leads to high complete response rates at 2 years and can be regarded as an evidence-based treatment modality for superficial growing non-melanoma skin cancer and the (pre)malignant AK. The Rotterdam fractionated approach should be included in future guidelines.

Quality of clinical practice guidelines in dermatological oncology.

BACKGROUND: Clinical practice guidelines are increasingly used. To determine the quality of guidelines the Appraisal of Guidelines and Research and Evaluation (AGREE) instrument was developed and introduced in 2001. The AGREE instrument consists of 23 criteria, grouped in six domains. OBJECTIVE: Assessment of quality of evidence-based guidelines in dermatological oncological care according to the AGREE instrument. METHODS: We searched MEDLINE, PubMed, EMBASE and Cochrane literature and relevant websites of guidelines development programmes and the national dermatological society to identify evidence-based dermatological guidelines especially in the treatment of to basal cell carcinoma, squamous cell carcinoma and melanoma. Twenty guidelines, published between 1990 and 2005, were appraised according to the AGREE instrument by three authors. Standardized domain scores were calculated as advised by AGREE. We compared guidelines published before 2002 with those published later. RESULTS: Domain scores in the domains Scope & Purpose and Clarity were scored best. Applicability and Editorial Independence were scored worst (see Table 1). In time a weak trend towards better guidelines was seen. This trend can be attributed to better scores in the domains Search Strategy and Level of Evidence which are closely related to evidence-based medicine. The increase in score is due to more explicitly mentioning the search strategy, possible conflict of interest and involvement of different specialties in development of the guideline. Using the Mann-Whitney test to compare guidelines published before the AGREE and afterwards only a statistically significant better score was found for the domain Clarity (P < 0.05; Table 2). CONCLUSIONS: Guidelines in dermatological oncological care are of reasonable quality according to the AGREE instrument. The domains in the AGREE instrument concern especially the methods of development of guidelines. The score according to AGREE can be improved by explicitly mentioning the different items. As clinical guidelines are regarded to be an important instrument to improve quality of care, improvements are needed.