Postzygotic mosaicism in basal cell naevus syndrome.

Basal cell naevus syndrome (BCNS) is an autosomal dominant disorder most commonly caused by a germline mutation in the Drosophila homologue of patched-1 gene (PTCH1). Here we describe a patient with clinical signs of BCNS, caused by postzygotic mosaicism of a PTCH1 mutation. We performed restriction fragment length polymorphism analysis and Droplet Digital polymerase chain reaction to determine the degree of mosaicism in different tissues of this patient. Our case shows that a relatively low-grade mosaicism can lead to clinical signs reminiscent of those caused by a germline mutation. This finding has important implications for genetic counselling and therefore is pivotal to recognize for dermatologists, as well as for clinical geneticists and clinical laboratory geneticists.

Photodynamic therapy vs. topical imiquimod for treatment of superficial basal cell carcinoma: a subgroup analysis within a noninferiority randomized controlled trial.

BACKGROUND: A recent noninferiority randomized controlled trial (RCT) indicated that imiquimod can be considered as superior to methylaminolevulinate photodynamic therapy (MAL-PDT) in the treatment of superficial basal cell carcinoma (sBCC). Knowledge of treatment effectiveness in subgroups of patients is of great value in clinical practice to select the most effective treatment for an individual patient with sBCC. OBJECTIVES: To explore whether the relative treatment effect of MAL-PDT and imiquimod is consistent across subgroups defined by patient and tumour characteristics. METHODS: Data were derived from a single-blinded, noninferiority, multicentre RCT comparing MAL-PDT, topical imiquimod and fluorouracil (ISRCTN79701845). Treatment success was defined as free of tumour recurrence at 12-month follow-up. Subgroup analyses were performed for subgroups defined by sex, age, tumour location and tumour size. RESULTS: Two hundred and two patients received MAL-PDT and 198 received imiquimod. The superiority of imiquimod vs. MAL-PDT was observed in subgroups of females, sBCC on the trunk and large tumours with risk differences in favour of imiquimod of 18·4% [95% confidence interval (CI) 7·8-29·0%], 21·0% (95% CI 10·9-31·1%) and 18·9% (95% CI 7·1-30·7%), respectively. Higher probability of treatment success for imiquimod vs. MAL-PDT was consistently found in all other subgroups with the exception of sBCC localized on the lower extremities in older patients. In the latter subgroup, the risk difference at the expense of imiquimod was -57·3% (95% CI -81·7% to -32·9%). CONCLUSIONS: Imiquimod remains the first-choice treatment for sBCC in terms of effectiveness. In older patients with sBCC on the lower extremities MAL-PDT might be preferred. Results should be interpreted carefully as subgroup analyses were exploratory and not driven by prior hypotheses.

Cost-effectiveness of topical imiquimod and fluorouracil vs. photodynamic therapy for treatment of superficial basal-cell carcinoma.

BACKGROUND: A recent noninferiority randomized trial showed that in terms of clinical effectiveness imiquimod was superior and topical fluorouracil noninferior to methylaminolaevulinate photodynamic therapy (MAL-PDT) for treatment of superficial basal-cell carcinoma (sBCC). Although it was expected that MAL-PDT would be more costly than either cream, a full cost-effectiveness analysis is necessary to determine the balance between effectiveness and costs. OBJECTIVE: To determine whether imiquimod or topical fluorouracil are cost-effective treatments for sBCC compared with MAL-PDT. METHODS: An economic evaluation was performed from a healthcare perspective. Data on resource use and costs were collected alongside the randomized clinical trial. The incremental cost-effectiveness ratio was expressed as the incremental costs per additional patient free of tumour recurrence. RESULTS: At 12 months follow-up, the total mean costs for MAL-PDT were €680, for imiquimod cream €526 and for topical fluorouracil cream €388. Both imiquimod and topical fluorouracil were cost-effective treatments compared with MAL-PDT. Comparing costs and effectiveness of both creams led to a incremental investment of €4451 to achieve an additional patient free of tumour recurrence. The acceptability curve showed that, for a threshold value of €4451, the probability of imiquimod being more cost-effective than topical fluorouracil was 50%. CONCLUSION: Based on the 12 months follow-up results, imiquimod and topical fluorouracil cream are more cost-effective than MAL-PDT for treatment of sBCC. Hence, substituting MAL-PDT with either imiquimod or topical fluorouracil results in cost savings; these savings will be larger for topical fluorouracil. Long-term follow-up effectiveness data are necessary to confirm the cost-effectiveness of imiquimod vs. topical 5-fluorouracil cream.

Aesthetic evaluation after non-invasive treatment for superficial basal cell carcinoma.

BACKGROUND: Cosmetic results following non-invasive treatments are difficult to compare. Although qualified objective scar assessment scales are available, they are not used in dermatological studies. Usually a 4-point scale is used in dermatological scars. The reproducibility of this method has never been evaluated. Moreover, significant specific scar characteristics are lacking. The patient and observer scar assessment scale (POSAS) is a scale qualified for the assessments of surgical scars. It has proven to be as reliable as the widely used Vancouver Scar Scale, but has the advantage that it includes the patient's opinion and specifies different scar characteristics. OBJECTIVE: Both methods were used to evaluate cosmetic results following non-invasive treatments of superficial basal cell carcinoma (BCC). METHODS: A total of 54 lesions following non-invasive treatment for BCC in 54 patients were evaluated with the traditional 4-point scale and the POSAS. RESULTS: The 4-point scale showed the best reproducibility and had an intra-class correlation coefficient (ICC) of 0.66 (95% CI: 0.52-0.77) for a single observer and 0.85 (95% CI: 0.77-0.91) for multiple observers. The ICC of the POSAS was 0.41 (95% CI: 0.21-0.58) for a single observer and 0.67 (95% CI: 0.45-0.81) for three observers. The scar characteristics, vascularity and pigmentation were most decisive for the overall opinion. CONCLUSION: The use of the 4-point scale is a valid method to compare scars of non-invasive dermatological treatments. Supplementary registering vascularity and pigmentation can be useful in future studies.

Trends in the incidence of basal cell carcinoma by histopathological subtype.

BACKGROUND: As a result of the high prevalence, basal cell carcinoma (BCC) causes a significant and expensive health care problem. OBJECTIVE: In this study, we evaluate the proportional increase in BCC by histological subtype over the last two decades. METHODS: We retrospectively reviewed all primary histological confirmed BCCs diagnosed in the Maastricht University Medical Centre in The Netherlands in the years 1991, 1999 and 2007. RESULTS: An annual increase of the number of BCCs of 7% for both genders was shown. The age-standardized incidence rates for BCC increased between 1991 and 2007 from 54.2 to 162.1 per 100, 000 men and from 61.7 to 189.8 per 100, 000 women. The proportion of superficial BCC increased significantly from 17.6% to 30.7%. CONCLUSION: The incidence of BCC is continuing to increase this century. The observed shift to the superficial histological subtype, which can be treated non-surgically, might reduce the workload in the busy dermatologists practice.

Pain during topical photodynamic therapy: uncomfortable and unpredictable.

BACKGROUND: The major drawback of the widely used photodynamic therapy (PDT) is treatment-related pain. OBJECTIVE: Gain insight into the intensity of and predictive factors for painful burning sensation associated with PDT. METHODS: A prospective cohort study was performed at the department of Dermatology in the Maastricht University Medical Centre in Maastricht, a reference centre for dermatological oncology in The Netherlands. A total of 141 lesions in 108 patients were included, treated from November 2008 until June 2009 with PDT for superficial basal cell carcinoma, Bowen's disease (BD) or actinic keratosis (AK). Painful burning sensation was scored based on an 11-point pain intensity numeric rating scale (PI-NRS) (0=no pain; 10=worst possible pain). RESULTS: The percentage of patients with a PI-NRS score over six was 32.6% and 37.9% during the primary and follow-up PDT session respectively. A total of 76.6% (95/124) of the patients was consistent in pain intensity score reporting. Factors associated with higher PI-NRS scores were treatment of AK or BD, tumour localization in the head/neck region, patient's age over 70, Fitzpatrick skintype I/II, photosensitizer 5-aminolevulinic acid and use of oral analgesics. After mutual adjustment of these factors, Fitzpatrick skintype remained the only independent predictor of PI-NRS scores during PDT. CONCLUSION: It remains difficult to decide which patients should be considered for pain relieving measures. The solution remains to support all patients treated with PDT with pain relieving techniques or to let the support of pain relieving measures depend on the reported pain score for the primary session.

Preoperative serum CA125 levels do not predict suboptimal cytoreductive surgery in epithelial ovarian cancer.

The objective is to assess the ability of preoperative serum CA125 levels to identify patients at high risk of suboptimal cytoreductive surgery for epithelial ovarian cancer (EOC). One hundred and thirty-two women diagnosed with EOC between 1998 and 2004, who had serum CA125 levels measured preoperatively and received primary cytoreductive surgery, were retrospectively evaluated. The value of CA125 and patient and disease characteristics to predict suboptimal cytoreduction were determined, and a prognostic scoring system, based on statistically significant variables, was created. Optimal cytoreduction was achieved in 42.7% of the women with FIGO stage III/IV EOC. The optimal cutoff point of preoperative CA125 to predict surgical outcome in this group was 330 U/mL (sensitivity 80.0%; specificity 41.5%). The area under the receiver-operating characteristic curve (AUC) for preoperative CA125 predicting suboptimal surgery in FIGO stage III/IV was 0.576 (P = 0.617). Preoperative radiologic amount of ascites and weight loss (ie, >or=10% in the last 6 months before diagnosis) were independent prognostic factors for suboptimal cytoreduction, showing an AUC of 0.76 (P < 0.001) in women with FIGO stage III/IV. A prognostic scoring system showed that the chance of suboptimal surgery was 84.6% in FIGO stage III/IV when both these factors are present preoperatively. The role of CA125 levels predicting suboptimal cytoreduction seems questionable. Instead, women with considerable weight loss and a gross amount of ascites have a higher risk of suboptimal cytoreduction. These patients may be candidates for neoadjuvant chemotherapy.