[Interest of immunohistochemic markers (Ki67, HMB45, p53) in risk analysis of congenital naevi of little and middle size]. / Intérêt des marqueurs immunohistochimiques (Ki67, HMB45, p53) dans l'analyse de risque des naevi congénitaux de petite et moyenne taille.

The risk to develop melanoma from small or medium size congenital naevus remain controversial. The main goal of the present study was to determine the interest of three immunohistochemical markers (Ki67, HMB45 and p53) in predicting malignant transformation of these congenital naevi and to see if a specific immunohistochemical profile of such transformed naevi can be identified. The markers (Ki67, HMB45 and p53) have been used retrospectively on sections of small or medium size congenital naevi (group NC, n = 15), of melanoma developed on small or medium size congenital naevi (group MNC, n = 15) and of melanoma developed on acquired naevi (group MNA, n = 15). The labelled cells have been counted in different cutaneous layers: junction, superficial dermal layer and deep dermal layer. No reactivity was observed for the three markers in group NC. The percentage of labelled cells was significantly different for the three markers between the group NC and the groups MNC and MNA. There was no difference between the groups MNC and MNA. In the groups MNC and MNA, a gradient in the percentage of labelled cells was observed between superficial and deep layers. These three markers do not differentiate melanoma developed from congenital naevi of small or medium size and melanoma developed from acquired naevi. Moreover, the results suggest that these three markers are useless in predicting the risk of malignant transformation of small or medium size congenital naevi.

[Management of cutaneous toxicities induced by epidermal growth factor receptor inhibitors: a review]. / Prise en charge des toxicités cutanées des thérapies dirigées contre les récepteurs du facteur de croissance epidermique: revue de la littérature.

The epidermal growth factor receptor (EGFR) is overexpressed in many solid tumors. Its inactivation has an inhibitory effect on the growth and spread of the tumoral cells. It therefore represents an attractive target to treat different cancers. Several molecules have already been registered while others are still under evaluation. One of the common side effects of these therapies is the development of cutaneous toxicities, more precisely a cutaneous rash, sometimes major and distressing. The physiopathology of these cutaneous side effects is poorly understood. Moreover a correlation between the severity of the rash and the tumoral response has been demonstrated in some studies. If this link is confirmed, the rash could be used as a marker for the anti-tumoral activity. This review will summarize the clinical presentations and the current recommendations for the management of cutaneous toxicities induced by EGFR inhibitors.

[Extracorporeal photochemotherapy: review of its mechanisms of action and clinical applications]. / La photochimiothérapie extracorporelle: revue de son mode d'action et de ses indications.

Extracorporeal photochemotherapy is an immunomodulatory treatment wich is carried out in three steps: first leukapheresis, then ex vivo PUVA treatment and finally autologous transfusion. Its current "evidence-based" indications are erythrodermic cutaneous lymphoma, graft versus host disease and cardiac graft rejection. However this treatment has already been used with success in many other diseases such as systemic sclerosis, multiple sclerosis, type 1 diabetes and various autoimmune dermatologic diseases. Randomised controlled studies are needed to confirm the efficacy of photopheresis in these diseases. We also review the different hypotheses explaining the mechanism of action of photopheresis.

Skin biopsies in DC vaccines for stage III-IV melanoma patients: role of neutrophils?

Dendritic cell (DC) vaccines are used for the induction of anti-tumor T cell reaction in melanoma patients. DC are generated in vitro, pulsed with antigen and matured prior to injection. They are supposed to migrate to lymph nodes and to present the processed antigen to naive T cells allowing activation of tumor-specific lymphocytes. It has been suggested that intradermal injection allows a superior migration to the lymph node. Eight HLA-A2 positive patients with stage III or IV melanomas expressing NA 17 antigen were collected. They were included in a pilot trial of vaccination in which they received IL3/INFb DC presenting the NA17 A2 antigen. In each patient, a skin biopsy was performed at the injection site, 24 h after inoculation. The striking features of the biopsies were the presence of a perivascular CD3+/CD8+ T cell infiltrate with a slight population of CD4+ cells and the presence of a massive neutrophilic infiltrate associated with the injected DC still present, realizing a suppurative granuloma. The persistence of DC 24 h after the injection suggests that migration in the lymph node is not necessary for the induction of the immune response. The skin itself could be the location of a reaction starting with a massive recruitment of neutrophils.

[The treatment of psoriasis: basic principles and new options]. / Le traitement du psoriasis: sa stratégie et les nouvelles options.

Psoriasis is a frequent chronic disease with a typical cutaneous expression described as erythemato-squamous lesions, and sometimes, joint involvement. This disorder rarely causes death in patients, but often alters their quality of life. A better understanding of the pathophysiology of psoriasis has led to the development of new therapeutic options among which are treatments targeted on blocking T-cell activation. Thanks to these therapies we can offer the patients long lasting remission, albeit not a curative approach. The therapeutic approach towards psoriasis will be selected in a multidisciplinary spirit, and after considering the patient himself, his disease and his lifestyle.

Impact of cosmetic care on quality of life in breast cancer patients during chemotherapy and radiotherapy: an initial randomized controlled study.

BACKGROUND: Breast cancer is the most common cancer in women and therefore represents a major problem in public health. Data from patients' self-report questionnaires provide valuable information about the side-effects that patients may view as having a significantly detrimental impact on their quality of life (QOL) and yet are not always recognized as important by healthcare professionals. Cosmetology is a specific care for patients and there is actually no scientific evidence regarding effects on QOL for women with breast cancer. OBJECTIVE: The purpose of this study is to assess the impact of cosmetic care on QOL in breast cancer patients during chemotherapy and radiotherapy. METHODS: We developed a prospective, multicentre, randomized, controlled study including 27 patients. All the patients had to fill in a French-validated dermatologic specific quality-of-life questionnaire to compare the QOL of the two groups, the cosmetic group and the control group, at three different times of the adjuvant treatment. RESULTS: The results show a statistically significant difference between the cosmetic group and the control group in two areas of QOL: mood state and self-perception of the disease. CONCLUSION: This study emphasizes the interest of cosmetic care in breast cancer patients. However, further larger trials are needed to confirm this study.

Fluorescence diagnosis of face-located basal cell carcinomas: a new dermatological procedure which may help the surgeon.

Cutaneous Fluorescence Diagnosis (FD) is a new promising dermatological procedure which is based on the combination of a local application of a photosensitizer such as 5-aminolevulinic acid (ALA) or its methyl ester (MAL) and the use of a light source (red light) adapted to the absorption spectrum of these molecules. The targeted photosensitization of skin cancers, particularily superficial and extensive lesions including superficial basal cell carcinoma and Bowen's disease, by ALA or MAL induced porphyrins leads to a selective red fluorescence which can be demonstrated by Wood's lamp. This technique may be useful either to define better the choice of margins or to detect earlier and or multifocal recurrences.

[The strategy of prevention and early detection of cutaneous melanoma]. / La stratégie de prévention et de dépistage du mélanome cutané.

Dermatology, and more specifically cutaneous oncology, has evolved from a descriptive science concept towards multifaceted medico-surgical medicine which is nowadays based not only on observation. In this view, the importance of prevention and early detection of skin cancers including cutaneous melanoma has been recognized and has created a new challenge. Thanks to this proactive approach, the improvement in the prognosis of newly diagnosed melanomas has been demonstrated, but many efforts have to be brought to reduce the incidence and the mortality of this potentially aggressive tumor.

Anti-tumor necrosis factor alpha-induced psoriasiform eruptions: three further cases and current overview.

The increasing use of anti-TNF-alpha agents led to a better knowledge of their side effects. Among the cutaneous reactions, psoriasiform eruptions are increasingly described. We encountered 3 further psoriasiform eruptions during anti-TNF-alpha treatment for rheumatologic conditions and review the literature in order to identify the common characteristics of these cases. We found 30 case reports by using a comprehensive search of the 1966-2005 Medline database with a wild variety concerning the psoriasis type of eruption, the anti-TNF-alpha agent, the treatment duration and the presence or absence of a personal or familial history of psoriasis. We conclude that a psoriasiform eruption during anti-TNF-alpha treatment seems to be a class effect, without any as yet known identified predisposing factors, but it is more often self-limited and does not require treatment discontinuation.

[Cutaneous side effects of a long-term treatment by hydroxyurea]. / Complications cutanées du traitement au long cours par l'hydroxyurée.

Hydroxyurea is an antitumour agent used most commonly to treat myeloproliferative disorders. We present a clinical observation illustrating different cutaneous side effects susceptible to occur during a long-term treatment by hydroxyurea : leg ulceration, oral ulcer and spinocellular carcinoma. This clinical observation is completed by a review of the literature published on the cutaneous side effects of hydroxyurea treatment.

Decreased immunoreactive maspin expression in intermediate thickness and thick primary melanoma lesions.

Maspin is a member of the serpin family of protease inhibitors. It is a 42 kDa cytoplasmic protein that is reported to have tumour suppressor activity. The loss of maspin gene expression is correlated with increased invasiveness and the risk of metastases in breast cancer. We studied maspin expression in primary melanoma lesions obtained from 76 patients. Immunostaining of 5 pm sections for maspin expression was obtained using the citrate antigen retrieval method. The extent of immunostaining was scored by recording the proportion of immunoreactive cells and the intensity of immunostaining. Our results demonstrated that maspin expression was down-regulated in intermediate thickness and thick melanoma lesions compared with thin lesions. These results suggest that loss of maspin expression might play a role in melanoma progression, invasion and metastatic dissemination. Further studies are needed to clarify the clinicopathological significance of maspin expression in melanoma.

High serum galectin-3 in advanced melanoma: preliminary results.

BACKGROUND: Galectin-3 (Gal-3) is a member of the family of beta-galactoside-binding mammalian lectins, and has been implicated in tumour invasion and metastatic process in vitro and in vivo. AIM: To determine whether an increase in serum Gal-3 production could be found in patients with advanced metastatic melanoma. METHODS: We collected 18 sera from patients with AJCC stage IV metastatic melanomas and 20 sera from healthy volunteers. Determination of Gal-3 was performed by ELISA, and in the group of patients with melanoma, these results were compared with the serum lactate dehydrogenase (LDH) and the C-reactive protein (CRP) concentrations. RESULTS: Gal-3 concentration was shown to be significantly higher in the group of patients with melanoma compared with healthy volunteers, and Gal-3 concentration was significantly correlated with both LDH and CRP in the melanoma group. We also selected four patients in the melanoma group for Gal-3 retrospective immunostaining analysis on cutaneous metastases. Two of these patients, who had a higher Gal-3 serum level, showed more intense staining and the other two patients, with a lower serum level of Gal-3, had moderate immunostaining, suggesting that at least part of serum Gal-3 might be produced by metastatic melanoma tissue. CONCLUSIONS: Gal-3 might play a role in melanoma progression and/or inflammation, and warrants further study.

Three percent diclofenac in 2.5% hyaluronan gel in the treatment of actinic keratoses: a meta-analysis of the recent studies.

Three percent diclofenac in 2.5% hyaluronan gel (DHA) is approved by the Food and Drug Administration (FDA) in the treatment of actinic keratoses (AK). We conducted a meta-analysis of the few prospective studies that evaluated the effect of DHA on the target lesion number score TLNS0 (indicating complete resolution of all target lesions in the treatment area) and/or the cumulative target lesion number score CLNS0 (indicating resolution of the target and new lesions in the treatment area) with assessment 30 days after the end of treatment. A comprehensive search of the 1966-2005 MEDLINE database and review of the reference lists of relevant articles identified the published randomised trials. Three studies were included, with a total of 364 patients. The placebo was the hyaluronan vehicle gel (HAV). The intention-to-treat analyses show that DHA significantly improve the TLNS0 (OR= 3.72; 95% CI=2.05-6.74) and the CLNS0 (OR=4.09; 95% CI=2.55-6.56) compare to HAV. Overall, 42/106 (39.6% CI: 30.8- 49.1%) had a TLNS0 with mean treatment duration of 75 days +/- 21 [mean+/-standard deviation (SD)], and 70/179 (39.1% CI:32.3-46.4%) patients had a CLNS0 with a mean 78 days+/-16 treatment duration. DHA is effective compared to HAV in the treatment of AK. Further studies should establish subgroup analyses according to sites and severity of the AK lesions in order to determine if more patients could be improved in restricted indications. Biopsies, a longer follow-up evaluation, and comparisons with the other treatments of AK will also be helpful in the future to define the place of this treatment in the management of AK.

Evaluation of extensive initial staging procedure in intermediate/high-risk melanoma patients.

INTRODUCTION: Early diagnosis and treatment of metastases have been shown to improve overall survival of melanoma patients. The purpose of this study was to evaluate the impact of extensive initial staging, including positron emission tomography (PET) scan on the management of melanoma patients. PATIENTS AND METHODS: Forty-three patients with intermediate/poor prognosis primary melanoma benefited from complementary excision and sentinel lymph node biopsy (SLB) after clinical and paraclinical staging (computed tomography, nuclear magnetic resonance and whole body fluorodeoxyglucose PET scan). RESULTS: No systemic metastases were demonstrated, while the SLB procedure emphasized the presence of regional lymph node metastases in 10 patients as suggested by the PET scan in four patients (sensitivity of the PET scan 40%). These 10 patients with early diagnosed lymph node involvement benefited from early surgery and were included in adjuvant treatment protocols. A secondary primary cancer was fortuitously diagnosed and treated early in two patients. CONCLUSIONS: The development of new adjuvant therapies and therapeutic procedures (specific and non-specific immunotherapy, gamma-knife radiosurgery, etc.) now raises the relevance of extensive staging in intermediate/poor prognosis melanoma patients. We confirm in our series that PET scan is not useful to detect micrometastasis and cannot replace SLB in initial regional staging. However, we show in our study that 12 of 43 patients were treated early or were included early in treatment protocols thanks to the extensive staging procedure. Nevertheless, it seems important to evaluate through larger prospective trials the real impact of these early diagnoses and new treatments on overall survival before defining new diagnostic and therapeutic guidelines.