Intraoperative dermoscopy features of subungual squamous cell carcinoma: a study of 53 cases.

BACKGROUND: Subungual squamous cell carcinoma (SU-SCC) is the most common malignant tumour of the nail unit. Intraoperative nail dermoscopy has been described only for pigmented tumours, onychomatricoma and glomus tumours. AIM: To establish a description of intraoperative dermoscopic features of SU-SCC. METHODS: A single-centre retrospective cohort of 53 SU-SCC cases over a 5-year period was reviewed by six examiners who individually scored 31 intraoperative dermoscopic features as present or absent. For each feature, the frequency and interobserver agreement was evaluated, then the data were compared and a consensus was reached. RESULTS: No feature had perfect or substantial interobserver agreement. Regarding anatomy and architecture, most tumours involved both the nail bed and nail matrix (n = 34, 64.2%) and had nonparallel lateral side edges (n = 36, 67.9%). Regarding vascular features, several different patterns were found: dotted vessels (n = 49, 92.5%), irregular vessels (n = 47, 88.7%), curved vessels (n = 46, 86.8%), sagittal vessels (n = 45, 84.9%), milky-red areas (n = 42, 79.2%), linear and regular vessels (n = 30, 56.6%), coiled and hairpin vessels (n = 23, 43.4%), and arborizing vessels (n = 16, 30.2%). Pigmented dermoscopy structures included dotted purpura, grey granulation and splinter haemorrhages, which were found in 49 (20.8%), 9 (17%) and 9 (17%) cases, respectively. Other dermoscopic signs were pink background, translucent structureless area, whitish scaly areas, distal plug, yellowish scales and dots, and 'digitiform' proximal edge, which were found in 49 (84.9%), 49 (84.9%), 43 (81.1%), 37 (69.8%), 28 (52.8%) and 22 (41.5%) cases, respectively. CONCLUSION: Analysis of this first large series of SU-SCC studied by intraoperative dermoscopy suggests that it gives useful information to better approach the diagnosis and to target biopsies.

Evaluation of large clinically atypical vulvar pigmentation with RCM: atypical melanosis or early melanoma?

BACKGROUND: Vulvar melanosis can occasionally be clinically challenging by mimicking an early melanoma. OBJECTIVE: To report our experience of initial evaluation and follow-up in this peculiar subset of vulvar melanosis using reflectance confocal microscopy (RCM). METHODS: We retrospectively evaluated 18 consecutive cases referred for atypical vulvar pigmentation or for which melanoma was considered and that underwent both RCM examination and histopathological assessment. In 13 cases with available dermoscopic pictures, RCM classification was compared to dermoscopic diagnosis, and in all cases, the density of melanocytes was evaluated on biopsies using MelanA immunostaining. RESULTS: Among the 18 atypical pigmented lesions, 17 vulvar melanosis and one melanoma were histologically determined. RCM concluded a benign vulvar melanosis in 10 of 17 cases, whereas dermoscopy did so in three of 12 cases. RCM identified the only early malignant lentiginous melanoma. In several cases of vulvar melanosis, RCM could identify foci of melanocytic hyperplasia in an otherwise benign pattern. CONCLUSIONS: In this clinically and dermoscopically challenging subset of vulvar pigmentations, RCM appears relevant for initial extensive evaluation, especially to target initial biopsy sampling, and to perform non-invasive monitoring of foci of melanocytic hyperplasia.

Ineffective anti PD-1 therapy after BRAF inhibitor failure in advanced melanoma.

BACKGROUND: Anti-PD-1 and BRAF-inhibitors (BRAFi) have been approved as first-line treatments in advanced melanoma. To date, no prospective data are available to give the best sequence of treatment. The objective of this study was to evaluate in real-life the efficacy of anti-PD-1 after BRAFi, ipilimumab, or chemotherapy failure. METHODS: This was a single institution cohort analysis in patients treated with anti-PD-1 right after BRAFi, ipilimumab, or chemotherapy failure. Melanoma evolution after anti-PD-1 initiation was analyzed in BRAF-mutated and BRAF wild-type patients. The efficacy of treatment was evaluated by Objective Response Rate (ORR), Disease Control Rate (DCR), Progression-Free Survival (PFS), and Overall Survival (OS). RESULTS: Seventy-four patients were included: 33 wild-type and 41 BRAF-mutated melanoma. ORR to anti-PD-1 was significantly lower in BRAF-mutated patients (12.2% vs. 45.5%, p = 0.002). After anti-PD-1 initiation, the median PFS and OS was significantly shorter in the BRAF mutated group (2 vs. 5 months and 7 vs. 20 months, p = 0.001). The hazard ratio for disease progression was of 2.3 (95%CI:1.3-3.9; p = 0.003) and 2.5 (95%CI:1.3-4.5; p = 0.005) for death. Thirty-nine percent of BRAF-mutated-patients died within 3 months after anti-PD-1 initiation. Rapid death (≤3 months) was significantly higher in BRAF-mutated patients (55.2% vs. 20.0%, p = 0.014). DISCUSSION: This is the largest series of unselected patients treated in real-life with anti-PD-1 as second-or-higher line of treatment. Anti-PD-1 was less effective in BRAF-mutated cases as a majority of patients presented aggressive tumor evolution after BRAFi discontinuation. These data are consistent with previous studies suggesting a negative impact of BRAFi prior to immunotherapy.

Dermoscopy, a useful tool for general practitioners in melanoma screening: a nationwide survey.

BACKGROUND: Dermoscopy improves diagnostic accuracy in melanoma, as shown by several meta-analyses. Although it is used by general practitioners (GPs) in Australia, Canada and Italy, no published data on this topic are available in France. OBJECTIVES: To review the opinions and use of dermoscopy by GPs in France and to understand their practice of skin examination. METHODS: We designed a descriptive and cross-sectional survey and conducted it between 26 November and 26 December 2014. An anonymous, multiple-choice questionnaire about the demographic characteristics, skin examination modalities and use and training in dermoscopy was sent to 4057 GPs in four large regions of France. Pearson, χ(2) , Student, Welch and Fisher tests were used for cross-tabulation statistical analysis. RESULTS: Only 8% of respondents had access to a dermoscope; most were male practitioners and aged > 50 years. Dermoscopy increased self-confidence in analysing pigmented lesions (P = 0·004), and dermoscopy users referred fewer patients to dermatologists. The number of biopsies was reduced in the dermoscopy users group (P = 0·004). In total, 425 questionnaires were returned and analysed. Dermoscopy users took more time to evaluate a single pigmented lesion (P = 0·015). Only 16·9% of physicians declared having received some training on dermoscopy, yet this number reached 47% for those owning a dermoscope. Their training was mostly short and recent. Overall 29·2% of the respondents said the main advantage was to reduce the number of referrals to the dermatologists (P = 0·004), while its main disadvantage was the necessity of training (54·6%). Our responders declared they could spend seven working days on a dermoscopy training course. CONCLUSIONS: Our study demonstrates positive opinions regarding dermoscopy, despite a minority of French GPs using this technique in the areas surveyed. The need for formal training appears to be the main limitation to wider use. Appropriate and specifically designed training programmes should be offered.

Overview of the use of dermoscopy in academic and non-academic hospital centres in France: a nationwide survey.

BACKGROUND: Dermoscopy is acknowledged to improve the diagnostic accuracy of melanoma by several concordant meta-analyses. However, the use of dermoscopy was not considered as a high level of evidence diagnostic tool by French Health Authorities. However, as shown in Australian, American and in our recent surveys, dermoscopy is used by most of dermatologists in private practice. OBJECTIVES: To analyse the use, beliefs, teaching given and research produced in dermoscopy in dermatology departments of French hospitals. METHODS: A questionnaire about the use, available equipment, teaching activities and published research on dermoscopy was mailed to all chairmen of dermatology departments in French both academic and non-academic hospitals. RESULTS: Seventy-six of 110 mailed questionnaires were returned. The majority of centres claimed to use dermoscopy (97.5%), but it seemed heterogeneous among practitioners according to their age and position. The use of dermoscopy was four times higher in non-academic centres (P = 0.015). Centres located in the south east of France were higher users comparing with others (P = 0.004). Earlier detection of melanoma was the most important advantage reported. Excessive training time was the most important reported disadvantage. Twenty-five percent of centres had dedicated clinics for pigmented lesions. Few centres (14.5%) run formal dermoscopy training programs. Most centres (74.7%) declared a use of dermoscopy for the diagnosis of non-tumoral diseases. CONCLUSIONS: This is the first European study evaluating the use of dermoscopy among hospital. Despite a large use, dermoscopy-dedicated teaching and research time appeared to be insufficient.

Dermoscopy use by French private practice dermatologists: a nationwide survey.

BACKGROUND: Dermoscopy is now recognized as an essential tool for discriminating melanoma from other pigmented lesions, as corroborated by several robust meta-analyses. Although it is considered to be widely used in European countries, no published data on this topic are available to date, unlike in Australia and the U.S.A. OBJECTIVES: To describe and quantify the use and learning of dermoscopy among French private practice dermatologists. METHODS: A questionnaire of 19 items regarding demographic characteristics, dermoscopy use and training, and physician's judgment on dermoscopy was mailed to all French private practice dermatologists. Only questionnaires with an answer to the key item, 'Do you use dermoscopy?' were taken into account. RESULTS: Of 3179 mailed questionnaires, 1611 were returned and 1576 were analysable (49·6%). Most respondents declared using dermoscopy (94·6%), using their dermoscope several times a day (82·7%) and/or for the diagnosis of nonpigmented lesions (87·7%). Physicians learned dermoscopy mainly through books (75·8%) and/or conferences (88·6%); 12·8% reported a dedicated university degree. Dermoscopy helps to detect melanoma earlier and to perform fewer biopsies according to 86·6% and 74·6%, respectively. On multivariate analysis, female sex and age under 45 years were significantly associated with higher utilization rate of dermoscopy [odds ratio 1·89, 95% confidence interval (CI) 1·15-3·10; and 2·85, 95% CI 1·14-7·11, respectively]. CONCLUSIONS: This is the first published nationwide survey of dermoscopy practice in Europe. Despite potential classification and/or selection bias, the particularly high penetration rate found in our study suggests that dermoscopy is now widely accepted by French private practice dermatologists for the routine management of both pigmented and nonpigmented lesions.

Features of pigmented vulval lesions on dermoscopy.

BACKGROUND: The dermoscopic criteria for benign and malignant lesions on the vulva are not well established due to the lack of large series of such lesions. Melanoma should always be included in the differential diagnosis of pigmented lesions on the vulva especially when they are wide, or of recent onset. Elsewhere on the skin dermoscopy plays an important role in the selection of suspicious pigmented lesions, as well as in the selection of the best site to perform the biopsy. OBJECTIVES: To analyse the dermoscopic patterns observed in pigmented lesions of the vulva. METHODS: We analysed a nonselected consecutive series of 68 histopathologically proven cases comprising five melanomas, 16 naevi, 20 lentigos, 12 benign vulval melanoses, 11 cases of postinflammatory pigmentation, three pigmented cases of usual vulval intraepithelial neoplasia (VIN) and one seborrhoeic keratosis seen at our institution. The dermoscope was covered by translucent disposable food wrap and/or antibacterial gel to prevent possible transmission of infections. Descriptive statistics were performed using multiple correspondence analysis. RESULTS: The parallel (37%), ring-like (9%), homogeneous (22%), globular-like (13%) and reticular-like (6%) patterns were observed on benign lesions (naevi, lentigo, vulval melanosis and postinflammatory pigmentation). The cerebriform pattern (6%) was observed only on VIN and seborrhoeic keratosis. The multicomponent pattern (6%) was associated with melanoma (60%). In cases of melanoma we also occasionally observed an irregular pattern, a whitish or blue-whitish veil, irregularly distributed dots and globules and atypical vascular pattern. Using multiple correspondence analysis, we designed a new algorithm for the early detection of vulval melanomas. CONCLUSIONS: Dermoscopy can play a role in the noninvasive classification of vulval melanosis. However, further studies of larger collaborative series are needed to validate our vulval melanoma diagnostic algorithm. VIN and seborrhoeic keratosis share the same dermoscopic features and biopsy should be considered for seborrhoeic-like keratosis. In case of doubt pathological examination of a biopsy remains mandatory.

Basal cell carcinomas and actinic keratoses seen in dermatological practice in France: a cross-sectional survey.

BACKGROUND: Most actinic keratoses (AKs) and a number of basal cell carcinomas (BCCs) cannot be assessed by pathological records. OBJECTIVE: To estimate prospectively the figures and characteristics of BCCs and AKs seen by French dermatologists, their medical load, and present a more realistic approach to their incidence. METHODS: A cross-sectional study conducted in France in a representative sample of dermatologists (n = 215). Out-patients seen for 1 or more BCCs or AKs were recorded over 4 non-consecutive weeks. RESULTS: Among 78,300 out-patients, 1,321 had 1 (or more) BCC, and 3,688 had 1 or more AKs (1 and 5% of consultations made by dermatologists). When extrapolating, the medical load in France was estimated at 248,000 and 693,000 consultations/year leading to a clinical diagnosis of BCC and AK, respectively. A total of 1,655 BCCs were diagnosed including 839 superficial (50.7%), 636 nodular (38.4%), 137 morpheiform (8.3%) and 43 other types (2.6%). Superficial and nodular BCCs were more frequently diagnosed with a small size (<10 mm) than morpheiform BCCs. CONCLUSION: Our study in France provides the first estimate of the clinical burden represented by AKs and BCCs in dermatology practice.

[Therapeutic modalities and economic assessment in the treatment of superficial basal cell carcinomas and multiple actinic keratoses by French dermatologists]. / Evaluation médico-économique de la prise en charge des carcinomes basocellulaires superficiels et des kératoses actiniques multiples par les dermatologues français.

INTRODUCTION: To date, no prospective studies have been conducted in France describing the management of actinic keratoses (AK) and superficial basal cell carcinomas (sBCC). The aim of the present study was to describe the therapeutic modalities for AK and sBCC adopted by French dermatologists and to determine the direct annual medical costs. PATIENTS AND METHODS: This was a prospective, observational study conducted in France between January and June 2004 in a random selection of representative dermatologists (n=202). The first 5 adult patients seen for one or more sBCCs and the first patient with at least 4 AKs over a period of four non-consecutive weeks were included in the study. The following data were recorded using a standardized questionnaire at inclusion: date of birth, gender, habitat, professional activity, social insurance regimen, site, number and maximum size of lesions. The therapeutic modalities, the physicians involved and the laboratory examinations during the 3 months following diagnosis were recorded prospectively. Medical management costs were calculated taking into account the usual parameters (e.g. French nomenclature of medical acts). RESULTS: 512 patients with sBCC (mean age: 69 years; sex-ratio M/F: 0.92) were included in the study. sBCC was isolated in 80% of cases, measured less than 2 cm in 90%, and was located on the head/neck in 51% and on the trunk in 37%. Histological confirmation of diagnosis of BCC was obtained in 85% of cases. Treatment comprised surgical excision in 70% of cases, cryotherapy in 13%, topical therapy in 7% and curettage/electrodessication in 4%. Clinical follow-up was performed in 79% of cases. The mean cost per patient over 3 months was 139 euros (CI95%: 125-153). In addition, 226 patients with AK (mean age: 76 years; sex-ratio M/F: 2.1) were included in the study. AKs were located on the head/neck in 74% of cases and on the trunk in 6%. Treatment consisted of cryotherapy in 92% of cases. The mean cost per patient over 3 months was calculated at 85 euros (CI95%: 71-99). An on-site audit of 5% of the investigators gave a concordance rate of 98.8%. DISCUSSION: This is the first study conducted in France to evaluate both the medical approach and treatment costs of sBCC and AK. Finally, the mostly surgical treatment of sBCC observed is in accordance with the recent French ANAES guidelines. When extrapolating the results of the present study, the annual cost of treatment of sBCC by French dermatologists may be estimated at between 10.2 and 10.6m euros.

Sentinel lymph node biopsy in melanoma: a micromorphometric study relating to prognosis and completion lymph node dissection.

BACKGROUND: Sentinel lymph node (SLN) positivity has been found to be strongly associated with a poor prognosis in melanoma. OBJECTIVES: This large referral centre study was conducted: (i) to confirm the powerful prognostic value of SLN biopsy (SLNB); (ii) to correlate patient prognosis to the micromorphometric features of SLN metastasis in SLN-positive patients; and (iii) to correlate these micromorphometric features to the likelihood of positive completion lymph node dissection (CLND). PATIENTS AND METHODS: SLNB was performed in 455 cases of primary melanoma between January 1999 and December 2004; for patients with positive SLN, the following micromorphometric features were registered: size of the largest metastasis (two diameters), depth of metastasis, number of millimetric slices involved, maximum number of metastases on a single section, presence of intracapsular lymphatic invasion and extracapsular spread. Kaplan-Meier survival curves were compared with the log-rank test; multivariate analysis was performed using a Cox regression model. Dependence of CLND status on micromorphometric features of SLN was assessed by the chi(2) test and predictive values of the different features were evaluated by multivariate analysis using a logistic regression model. RESULTS: A positive SLN was identified in 98 of our 455 cases. Survival was significantly shorter in SLN-positive patients than in SLN-negative patients. Extracapsular invasion was found to be an independent prognostic factor of disease-free survival; ulceration of the primary and the maximum diameter of the largest metastasis were identified as independent predictive factors of disease-specific survival. Age and the lowest diameter of the largest metastasis were identified as independent predictive criteria of positive CLND, whereas depth of metastasis was not. Positivity of CLND was not significantly associated with a worse prognosis. CONCLUSIONS: Our study confirms the previously demonstrated strong prognostic value of SLNB. It also confirms the relationship between tumour burden in the SLN (evaluated by the maximum diameter of the largest metastasis) and clinical outcome. We point out a new micromorphometric feature of SLN, which seems to be predictive of CLND status: the lowest diameter of the largest metastasis.

[A new tool for evaluation of medication errors applied to pediatric hematology]. / Un nouvel outil d'évaluation de l'iatrogénie médicamenteuse, appliqué à l'hématologie pédiatrique.

This study was conducted in a haematological paediatric department and was aimed at evaluating drug medication errors. Their frequency was studied, but also and mainly their degree of severity and preventability. Only adverse drug events that were identified as possibly due to pharmacological properties of drugs or medication errors were collected. An original method was used, based on a multidimensional mathematical tool, called Factorial Analysis of Multiple Correspondences (FAMC), in order to assess the grade of severity and preventability for each adverse drug event. A total of 155 adverse drug events were detected for 34 out of 52 patients hospitalized during the study period. The prevalence rate was 65 per cent and among these adverse drug events, 16 per cent were serious and 53 per cent were avoidable. Apart from the fact that the FAMC helped to determine the grade of preventability, FAMC allowed one to demonstrate that allergy and medication errors were the most avoidable adverse drug events. In this way the method used was validated. This study permitted the assessment of drug medication errors in this department and helped to choose the priorities for the management of preventive actions.

Mass screening programs for breast cancer in France--average values of assessment criteria.

Breast cancer is the most common cancer in women worldwide. Many studies have been performed worldwide to assess the effectiveness of screening in terms of reduced mortality due to breast cancer. Since the end of 1989, 10 breast cancer mass screening programs using mammography have been carried out in France under the sponsorship of the National Fund for Health Prevention, Education, and Information (FNPEIS) from the National Health Insurance of Salaried Workers (CNAMTS). These 10 campaigns, which are on a district scale, are organized according to variable methods and are assessed using a common procedure. Four groups of criteria are measured in this procedure, which investigates the impact, quality, effectiveness, and costs of screening programs. The average and extreme values of each criterion as calculated from the campaigns are presented in this paper. In order to enlighten the judgment on the French results, a comparison with the international standards in force and with the results of foreign screening programs is proposed.

[Mass screening programs for breast cancer in France. Comparative evaluation]. / Les programmes de dépistage de masse du cancer du sein en France. Evaluation comparative.

OBJECTIVE: The purpose of this work was to comparatively assess the results of mass screening programs for breast cancer implemented in six French departments in 1986, within the scope of the National Fund for Health Prevention, Education and Information of the National Health Insurance Office of Salaried Workers. MATERIAL AND METHODS: The data collected by the screening centres were analyzed by ten assessment teams that were independent from the program promotion staff, all using the same evaluation form. A complementary population study performed in eight French districts then, allowed assessing the frequency of self-referred screening (mammography performed out of program). RESULTS: The rate of participation in screening programs, in relation to the invited population, ranged from 21 to 48%, according to the district (36% in average). This low participation was probably related to the extent of self-referred screening. In fact, 19 to 40% of women, according to the district, had previously had a screening mammographic coverage: rate was around 68% in women aged 50 to 69 years. Positive findings with mammography ranged from 4.5 to 15.8% (10.1% in average), while intervention rates ranged from 0.7 to 1.6% and detection rates from 3.8 to 6.2%. The ratio between benign tumors and cancers ranged from 0.7 to 2.1 according to the district. In order to enlighten the judgement on French results, we propose a comparison with the international standards in force. CONCLUSION: The various experiences with breast cancer screening in France show that this screening is technically feasible on the basis of existing medical structures. However, some criteria are still below the expected values, especially if compared with international standards. This result is probably accounted for by the high rate self-referred screening before age 40 in France. In these conditions, the question is whether extending breast cancer screening programs in France is an appropriate course of action.

[Economic evaluation of screening for neuroblastoma]. / Evaluation économique du dépistage du neuroblastome.

Though neuroblastoma, a cancer occurring in children, is infrequent, several countries run screening programs to detect it early since advanced stages show high mortality rates. The aim of this study is to propose a non empirical medico-economic evaluation model for the screening program for neuroblastoma, adaptable to various contexts. A marginal cost-effectiveness analysis was performed. The effectiveness and cost criteria were respectively the number of children who do not die from neuroblastoma and the cost of the screening programs, together with the cost of the treatments. The major parameters of the model were: size of target population, incidence, over-incidence rate, compliance rate, test sensitivity, distribution of cases and mortality rates according to the stage of the disease. The aim of the model was to determine, within a specific context (fixed parameters), the cost of an additional life saved, or less pragmatically to calculate the threshold values for the parameters for which the screening program for neuroblastoma is worthwhile (ie marginal cost equal to zero). We illustrate this model presentation with simulations elaborated from the neuroblastoma screening program performed in the Rhône area, France.

[Experience in mass screening of breast cancer with mammography in France]. / Les expériences de dépistage de masse du cancer du sein par mammographie en France. Un protocole commun d'évaluation.

In the framework of the National Fund for Prevention, Health Education and Information, the setting-up in France, on an experimental basis, of mass breast cancer screening programs by mammography in ten departments leads to suggest a common protocol for the evaluation of these programs, before an eventual generalization to the whole country. These programs are based on common principles: local screening based on existing medical facilities, single view mammography with double reading. However, the screening organisation is different in each department according to the target population, the screening interval, the mode of invitation, the methods for arranging double reading, etc. The purpose of this article is to report on the work of the evaluation group of the ten programs, and to propose a methodology for comparing the screening experiences in order to measure the role of the organisation methods. It gives definitions and modes of calculations for the evaluation criteria in four fields: impact, quality, efficacy and cost (with details about the feasibility of data collection) and proposes a reflection on analysis techniques in order to develop an optimum mass screening strategy.