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Biomedical subjects

C Vilmer

Publications and source records attributed to C Vilmer.

At least 19 recordsLinked to original sources

Divergence between the high rate of p53 mutations in skin carcinomas and the low prevalence of anti-p53 antibodies.

Circulating anti-p53 antibodies have been described and used as tumoural markers in patients with various cancers and strongly correlate with the p53 mutated status of the tumours. No study has yet looked at the prevalence of such antibodies in skin carcinoma patients although these tumours have been shown to be frequently p53 mutated. Most skin carcinoma can be diagnosed by examination or biopsy, but aggressive, recurrent and/or non-surgical cases' follow up would be helped by a biological marker of residual disease. We performed a prospective study looking at the prevalence of anti-p53 antibodies using an ELISA technique in a series of 105 skin carcinoma patients in comparison with a sex- and age-matched control skin carcinoma-free group (n = 130). Additionally, p53 accumulation was studied by immunohistochemistry to confirm p53 protein altered expression in a sample of tumours. Anti-p53 antibodies were detected in 2.9% of the cases, with a higher prevalence in patients suffering from the more aggressive squamous cell type (SCC) of skin carcinoma (8%) than for the more common and slowly growing basal cell carcinoma type or BCC (1.5%). p53 protein stabilization could be confirmed in 80% of tumours studied by IHC. This low level of anti-p53 antibody detection contrasts with the high rate of p53 mutations reported in these tumours. This observation shows that the anti-p53 humoral response is a complex and tissue-specific mechanism.

Adult↗

Delays in diagnosis and melanoma prognosis (II): the role of doctors.

A prospective survey was conducted to assess physician responsibility in melanoma prognosis. Consecutive patients with primary melanoma were interviewed and examined using a standardized questionnaire. Main outcome measures were medical components of the delay before tumor resection and tumor thickness. Of 590 melanomas, 29.1% were coincidentally detected by physicians and their tumor depth was lower than in melanomas detected by patients (p < 0.001). Physician sensitivity for melanoma diagnosis was evaluated at 86%. Median time intervals to propose resection and to perform removal of melanoma were short: 0 (mean 103) and 7 (mean 68) days, respectively. Melanomas were managed in an inappropriate way in 14.2% of cases. Location on acral areas and absence of pigmentation were associated with longer medical delays and more frequent inappropriate medical attitudes. Melanomas located on hardly visible areas were less frequently detected by physicians than those on visible areas. Medical delays were shorter, doctor's attitude was more frequently appropriate, and melanoma thickness was lower (p < 0.001) when the patient visited a dermatologist (54.7%) than when he or she visited a general practitioner (33.4%). Our study shows that doctor responsibility accounts for only a small part of the total delay before melanoma removal. However, systematic total examination and better training of doctors, especially about unusual forms of melanoma, could still improve melanoma detection.

Attitude of Health Personnel↗

Delays in diagnosis and melanoma prognosis (I): the role of patients.

A prospective survey was conducted to assess the role of patients in the melanoma prognosis. Consecutive patients with primary melanoma were interviewed and examined using a comprehensive questionnaire including a psychological instrument. Main outcome measures were the delay before medical intervention and the tumor thickness. Of 590 melanomas, 70.8% were detected by patients and this proportion was higher in females. Relatives were involved in the detection of half of the cases. Median delays before the patient realized he had a suspicious lesion, before this lesion was seen by a doctor, and before the melanoma was removed were 4 months, 2 months, and 1 week, respectively. Delays up to several years were observed in some cases. The rate of self-detection tended to be lower, the delays before seeking medical advice to be longer, and the tumor thickness to be higher in old people, in males, in lower-educated individuals, in those living out of towns, and in people with a low awareness about melanocytic tumors than in other cases. Conversely, individuals with a high number of atypical nevi, those who were aware to be at risk, and those who regularly visited a dermatologist tended to detect their melanoma more rapidly. No specific psychological traits were associated with a late reaction, although negligence and anxiety tended to prolong the delays. Knowledge about melanoma was poor in many patients, especially in males, and wrong beliefs were widespread. This study provides the targets of future education programs.

Adolescent↗

[Standards, Options and Recommendations (SOR): clinical practice guidelines for diagnosis, treatment and follow-up of cutaneous melanoma. Fédération Nationale des Centres de Lutte Contre le Cancer].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature systematic review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of Standards, Options and Recommendations for the management of patients with cutaneous melanoma. METHODS: Data have been identified by literature search using Medline - until December 1998 - and the personal reference lists of the expert group. Once the guidelines were defined, the document was submitted for review to national and international independent reviewers and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations for the management of cutaneous melanoma (CM) are: 1) The primary prevention of melanoma is based on a reduction in exposure to ultraviolet rays (solar or artificial). 2) The diagnosis of CM requires the surgical removal and histological examination of the lesion (standard). 3) The pathological report must include the diagnosis of primary malignant melanoma, the maximum thickness of the tumour in millimeters (Breslow), the clearance of surgical margins, the level of invasion (Clark), the presence and extension of regression and the presence of any ulceration (standard). 4) The standard treatment of a primary melanoma without lymph node involvement is based on surgery that must ensure adequate margins depending on the thickness of the tumour (standard, level of evidence B). 5) After surgery of a stage I melanoma, there is no indication for additional treatment outside a prospective therapeutic study (standard, level of evidence B, French Consensus Conference). 6) For a local recurrence without node involvement, in the absence of other metastases, surgical excision is the standard treatment. 7) In the case of metastatic regional lymph nodes, a complete regional lymphadenectomy is required. There is no indication for additional treatment outside a prospective therapeutic study (standard, level of evidence B). The inclusion of these patients in controlled studies of immunotherapy is recommended. 8) There is no standard therapeutic strategy for metastatic melanoma. Conventional palliative treatment is chemotherapy with dacarbazine (level of evidence B). 9) Follow-up is based on physical examination (standard). Patient information must encourage self-surveillance. Clinical surveillance and self-detection are indicated in all cases throughout life (standard).

Follow-Up Studies↗

P16 UV mutations in human skin epithelial tumors.

The p16 gene expresses two alternative transcripts (p16alpha and p16beta) involved in tumor suppression via the retinoblastoma (Rb) or p53 pathways. Disruption of these pathways can occur through inactivation of p16 or p53, or activating mutations of cyclin dependant kinase 4 gene (Cdk4). We searched for p16, Cdk4 and p53 gene mutations in 20 squamous cell carcinomas (SSCs), 1 actinic keratosis (AK), and 28 basal cell carcinomas (BCCs), using PCR-SSCP. A deletion and methylation analysis of p16 was also performed. Six different mutations (12%) were detected in exon 2 of p16 (common to p16alpha and p16beta), in five out of 21 squamous lesions (24%) (one AK and four SCCs) and one out of 28 BCCs (3.5%). These included four (66%) ultraviolet (UV)-type mutations (two tandems CC : GG to TT : AA transitions and two C : G to T : A transitions at dipyrimidic site) and two transversions. P53 mutations were present in 18 samples (37%), mostly of UV type. Of these, only two (one BCC and one AK) harboured simultaneously mutations of p16, but with no consequence on p16beta transcript. Our data demonstrate for the first time the presence of p16 UV induced mutations in non melanoma skin cancer, particularly in the most aggressive SCC type, and support that p16 and p53 are involved in two independent pathways in skin carcinogenesis.

Alternative Splicing↗

Melanoma and tumor thickness: challenges of early diagnosis.

OBJECTIVE: To test the basic assumption of campaigns for early diagnosis of melanoma, ie, prognosis is correlated with the delay in the diagnosis. DESIGN: Prospective study of the correlation between delays to diagnosis, assessed using a questionnaire, and the Breslow thickness as a prognosis marker. SETTING: Dermatology departments in France. PATIENTS: Five hundred ninety consecutive patients, referred within 12 weeks after resection of cutaneous melanoma. MAIN OUTCOME MEASURES: Assessment of 5 successive time intervals from the first time the patients realized that they had a lesion until the resection of the melanoma, and results of the correlation between each time interval and tumor thickness (Breslow). RESULTS: There is a positive but weak correlation between tumor thickness and the delay to identify a lesion as suspicious (r = 0.17; P = .009). However, this delay tends to be short for the thickest tumors. There is a negative correlation between tumor thickness and the delay to seek medical attention (r = -0.20; P<.001). This delay was shorter for nodular melanoma. No correlation is found between melanoma thickness and physicians' delays. CONCLUSIONS: Poor prognosis can be accounted for by aggressive rapidly growing tumors rather than by delays. In well-informed populations, campaigns for early diagnosis of melanoma may thus no longer have a major impact on prognosis, unless they are focused on subgroups less accessible to information and medical care.

Female↗

Chronic radiodermatitis following cardiac catheterisation: a report of two cases and a brief review of the literature.

Cardiac angiography produces one of the highest radiation exposures of any commonly used diagnostic x ray procedure. Recently, serious radiation induced skin injuries have been reported after repeated therapeutic interventional procedures using prolonged fluoroscopic imaging. Two male patients, aged 62 and 71 years, in whom chronic radiodermatitis developed one to two years after two consecutive cardiac catheterisation procedures are reported. Both patients had undergone lengthy procedures using prolonged fluoroscopic guidance in a limited number of projections. The resulting skin lesions were preceded, in one case, by an acute erythema and took the form of a delayed pigmented telangiectatic, indurated, or ulcerated plaque in the upper back or below the axilla whose site corresponded to the location of the x ray tube during cardiac catheterisation. Cutaneous side effects of radiation exposure result from direct damage to the irradiated tissue and have known thresholds. The diagnosis of radiation induced skin injury relies essentially on clinical and histopathological findings, location of skin lesions, and careful medical history. Interventional cardiologists should be aware of this complication, because chronic radiodermatitis may result in painful and resistant ulceration and eventually in squamous cell carcinoma.

Aged↗

Analysis of alterations adjacent to invasive vulvar carcinoma and their relationship with the associated carcinoma: a study of 67 cases.

A retrospective analysis of histological lesions adjacent to 67 invasive vulvar squamous cell carcinomas (SCC) was undertaken to analyse their nature, as well as their relationship to SCC. Patient age, clinical presentation and histological type of carcinoma, ISSVD classification of its adjacent lesions, disease-free and overall survival were reviewed. Severe undifferentiated vulvar intra-epithelial neoplasia (VIN3) was found in 19.4% of cases and vulvar lichen sclerosus (VLS) in 76.1% of cases. All VLS, except 2 cases, were associated with squamous cell hyperplasia (SCH), and a concomitant differentiated VIN was found in 76.6% of cases. Undifferentiated VIN3 was never associated with VLS. VLS was significantly associated with a keratinizing, well-differentiated SCC (98% of cases), while undifferentiated VIN3, was linked preferentially to 2 other types of SCC: in 77% of cases, a moderately-differentiated SCC with the same histological features as the so-called basaloid carcinoma and, in 23% of cases, a well-differentiated SCC with a variable extent of koilocytic atypia, similar to the so-called warty carcinoma. Carcinoma of the fourchette was more often associated with undifferentiated VIN3. Disease-free and overall survival were significantly better for carcinoma associated with undifferentiated VIN3 (p < 0.01 and p < 0.05, respectively). These findings suggest invasive vulvar SCC occurs on 2 distinct types of vulvar lesions: differentiated VIN and/or SCH associated with VLS and undifferentiated VIN3. Furthermore, the histological type of the carcinoma seems to differ according to adjacent lesions.

Adult↗

Failure of isotretinoin and interferon-alpha combination therapy for HPV-linked severe vulvar dysplasia. A report of two cases.

BACKGROUND: Retinoids (RA) and interferon (IFN) have been reported to be active against a variety of tumors and human papillomavirus (HPV)-related lesions. Because chronic and recurrent HPV-linked vulvar intraepithelial neoplasia 3 (VIN 3) have a high risk of invasion, we evaluated combined therapy of IFN-alpha with 13-cis-retinoic acid (13 cRA) in the treatment of two VIN 3 cases of this type. CASE: Two patients with chronic and recurrent VIN 3 were treated with combined therapy of IFN-alpha (4.5 x 10(6) five times a week) and 13 cRA (1 mg/kg/d) for six months. Clinical regression was observed at the end of treatment in both cases, but histologic features of VIN 3 were still present. CONCLUSION: These data demonstrate the ineffectiveness of the combined regimen of IFN-alpha and 13 cRA with this schedule for a period of six months in recurrent and chronic VIN 3.

Adult↗

[Comparison of the analgesic efficacy of EMLA 5% cream and lidocaine infiltration for biopsy of the genital mucosa].

OBJECTIVE: To compare the analgesic efficacy of EMLA 5 p. 100 cream versus Xylocaïne 1 p. 100 infiltration for biopsies of the genital mucosa. PATIENTS AND METHODS: 63 adult patients were randomized. EMLA (0.3-5 g) was applied during 7-12 minutes, and Xylocaïne 1 p. 100 (0.2-5 ml) was infiltrated 0-10 minutes before biopsy. Pain during the anaesthetic procedure and the biopsy was assessed by the patient using a Visual Analogue Scale. RESULTS: Pain scores were significantly lower with EMLA application than Xylocaïne infiltration, but infiltration resulted in better surgical anaesthesia. The combined pain scores (anaesthetic procedure and biopsy) were lower in the EMLA group, but this difference failed to reach statistical significance. CONCLUSION: EMLA is a less painful anaesthetic procedure than infiltration, but has a lower analgesic efficacy. EMLA can be used as an alternative to infiltration for biopsies of the genital mucosa.

Adult↗

Thin melanomas with unusual aggressive behavior: a report on nine cases. Melanoma Group of French Federation of Cancer Centers.

BACKGROUND: The major factor influencing the prognosis of cutaneous malignant melanoma (MMs) is the maximum thickness of the tumor as measured by Breslow's method. However, it has been reported that thin melanomas, which should have an excellent prognosis, may have the potential to metastasize, some with an unusually rapid course. OBJECTIVE: Our purpose was to examine prognostic indicators in relation to unusually rapid aggressive behavior in patients with thin MMs (<0.76mm). METHODS: We describe nine cases of thin MM (<.76mm) that exhibited a recurrence or metastasis during a follow-up period ranging from 3 to 10 years, among computerized records of 1118 MMs treated in a multicenter epidemiologic study. The data obtained from these nine cases were compared with nonrecurring thin MM (149 cases) of the same cohort. RESULTS: The particular aggressiveness of these thin melanomas was reflected by the short disease-free interval (3 years or less) in all ine patients. The recurring thin MM more frequently involved head and neck sites, occurred in male patients, and showed Clark's level III and IV. CONCLUSION: Our review suggests that the head and neck area is particularly involved by unusually rapidly recurring thin MM. Possible explanations are the specific problems of surgical management and the greater sun exposure of this location.

Adult↗