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Biomedical subjects

Sergio Chimenti

Publications and source records attributed to Sergio Chimenti.

At least 19 recordsLinked to original sources

WHO-EORTC classification for cutaneous lymphomas.

Primary cutaneous lymphomas are currently classified by the European Organization for Research and Treatment of Cancer (EORTC) classification or the World Health Organization (WHO) classification, but both systems have shortcomings. In particular, differences in the classification of cutaneous T-cell lymphomas other than mycosis fungoides, Sezary syndrome, and the group of primary cutaneous CD30+ lymphoproliferative disorders and the classification and terminology of different types of cutaneous B-cell lymphomas have resulted in considerable debate and confusion. During recent consensus meetings representatives of both systems reached agreement on a new classification, which is now called the WHO-EORTC classification. In this paper we describe the characteristic features of the different primary cutaneous lymphomas and other hematologic neoplasms frequently presenting in the skin, and discuss differences with the previous classification schemes. In addition, the relative frequency and survival data of 1905 patients with primary cutaneous lymphomas derived from Dutch and Austrian registries for primary cutaneous lymphomas are presented to illustrate the clinical significance of this new classification.

Humans↗

Imiquimod treatment of superficial and nodular basal cell carcinoma: 12-week open-label trial.

BACKGROUND: Imiquimod is an immune response modifier shown to be effective in basal cell carcinoma (BCC). OBJECTIVE: To evaluate the efficacy, tolerability, and response durability of imiquimod 5% cream in selected patients with superficial and/or nodular BCCs. METHODS: Seventy-five superficial and 19 nodular BCCs in 49 patients were treated with imiquimod once daily three times a week for up to 12 weeks. RESULTS: Of the 49 enrolled patients, 1 discontinued the study and 1 was lost to follow-up. After 12 weeks of treatment, a complete response occurred in 70 of 75 (93.3%) superficial BCCs and a partial response in 4 of 75 (5.3%) superficial BCCs. Ten of 19 (52.6%) nodular BCCs cleared after 12 weeks, whereas 7 (36.8%) showed partial remission. Adverse side effects were limited to local skin reactions. Recurrence was observed in 2 of 70 (2.9%) successfully treated superficial BCCs 6 and 8 months after treatment discontinuation. No recurrence was detected in 68 of 70 (97.1%) superficial BCCs and in 10 successfully treated nodular BCCs after 12 to 34 months of follow-up (mean 23 months). CONCLUSIONS: In our patient population, treatment of superficial BCCs with topical imiquimod for 12 weeks produced an excellent clinical response overall, with complete remission maintained after a mean of 23 months.

Adjuvants, Immunologic↗

Teledermatology: just cool or a real tool?

Telemedicine is the practice of healthcare using interactive audio, visual and data communication. This includes healthcare delivery, diagnoses, consultation and treatment as well as education and transfer of medical data. The transmission of multimedia streams has remained a major challenge. Although the Internet remains basically insecure, technology allows today to define and implement complete security profiles for specific (medical) communities. Data security is a must as in all other areas of applied medicine. Teledermatology offers possibilities in consulting, continuous medical education or teleteaching. In the future, consulting and asking for a second opinion will be the gold standard of medical care. The quality of healthcare will be improved without saving direct costs. However, indirect costs such as time and effort for the patient and the citizen will be reduced.

Dermatology↗

Treatment of lentigo maligna with tazarotene 0.1% gel.

We report 2 elderly patients with facial lentigo maligna who experienced complete regression, both clinically and histopathologically, after once-daily topical treatment with tazarotene 0.1% gel for 6 to 8 months. After a follow-up period of 18 and 30 months, no recurrence was observed. We believe that tazarotene might be considered as an alternative medical approach in selected patients with lentigo maligna.

Aged↗

Constitutional and environmental risk factors for cutaneous melanoma in an Italian population. A case-control study.

The aim of this study was to determine the relative risk for cutaneous melanoma associated with phenotypic and environmental variables in a population in central Italy and to assess how the combination of the different risk factors contributes to the overall risk for melanoma. We performed a case-control study of 100 patients with sporadic cutaneous melanoma and 200 controls matched for sex, age, ethnicity and residential area. Individuals were interviewed concerning pigmentary traits and sun exposure, and underwent a total body skin examination. Logistic regression models were used to evaluate the association between cutaneous melanoma and constitutional and environmental variables. The strongest risk factors were prolonged recreational sun exposure (odds ratio [OR] 5.010, 95% confidence interval [CI] 2.110-11.891), the presence of clinically atypical naevi (OR 4.916, 95% CI 2.496-9.995) and the presence of >50 common melanocytic naevi (OR 4.684, 95% CI 2.442-9.231). In addition, occupational sun exposure (OR 2.573, 95% CI 1.399-4.732), light brown hair (OR 2.336, 95% CI 1.328-4.138), high density of solar lentigos and/or actinic keratoses (OR 1.824, 95% CI 1.0-3.510) and type II, fair skin (OR 1.815, 95% CI 1.031-3.193) and blue eyes (OR 1.757, 95% CI 1.0-3.477) were each significantly associated with cutaneous melanoma risk. The combination of individual strong risk factors was associated with up to a 46-fold increase in the risk for cutaneous melanoma. Selected pigmentary traits, sun exposure and melanocytic naevi, individually and in combination, are important risk factors for cutaneous melanoma in an Italian population.

Adolescent↗

Evidence of increased apoptosis and reduced proliferation in basal cell carcinomas treated with tazarotene.

A preliminary clinical experience suggested tazarotene, a new acetylenic retinoid, as an effective alternative topical treatment of basal cell carcinomas (BCC). The mechanisms of action of this synthetic retinoid, however, have not been yet clarified. In this work we assessed the in vivo effects of daily application of tazarotene for 24 wk, on 30 small superficial and nodular BCC, and the in vitro effects of tazarotene on immortalized basal and squamous tumor epidermal cells. Cellular proliferation, apoptosis and changes in expression of retinol and retinoic acid receptors (RAR), p53, bcl-2, and bax were studied by immunohistochemistry, western blotting and PCR. Overall, 76.7% of treated tumors showed >50% regression. Complete healing was observed in 46.7% of all treated BCC, without recurrences at 2-y observation. Regression was associated with reduced proliferation and increased apoptosis, demonstrated by Ki-67- and TdT-mediated dUTP-biotin nick-end labelling-positive nuclear staining, and with enhanced RAR-beta and bax expression, with RAR-alpha and -gamma expression unchanged. In vitro, tazarotene induced a concentration-dependent increase of RAR-beta and bax associated with a greater rate of apoptosis and growth inhibition in basaloid tumor cells compared with squamous tumor cells. Our studies provide convincing evidence that tazarotene induces BCC regression possibly by synergistic RAR-beta-dependent anti-proliferative and pro-apoptotic pathways.

Adult↗

Psoriatic arthritis and CARD15 gene polymorphisms: no evidence for association in the Italian population.

Psoriatic arthritis (PsA) has been defined as an inflammatory arthritis associated with psoriasis that may affect as many as 30% of psoriasis patients. Epidemiological study reported strong familial clustering of PsA although the precise etiology of PsA is poorly understood. Recently, a genomewide linkage scan in PsA revealed a LOD score of 2.17 on chromosome 16q and provided strong evidence for a paternal imprinting effect. That region surrounds a psoriasis susceptibility locus including the CARD15 gene which has convincingly been shown to confer susceptibility to Crohn's disease. The existence of a common susceptibility gene for psoriasis/PsA and Crohn disease was recently demonstrated by evidence of association of CARD15 polymorphisms with PsA. To confirm these results in an independent population, we analyzed a data set of 193 Italian PsA patients and 150 controls for CARD15 polymorphisms (R702W, G908R and leu1007finsC) previously demonstrated associated with PsA. Here we report no evidence for association in the examined population for CARD15 polymorphisms, suggesting that the positive association previously reported in a genetically isolated population was the result of a linkage disequilibrium due to a founder effect.

Arthritis, Psoriatic↗

The p73 gene is an anti-tumoral target of the RARbeta/gamma-selective retinoid tazarotene.

Tazarotene, a member of the new class of acetylenic retinoids, has been shown to be effective in the treatment of several hyperproliferative skin diseases, including non-melanoma skin cancer. Its effectiveness is thought to rely on the ability to activate retinoic acid receptors beta and gamma and to induce a number of downstream anti-proliferative genes. Here, we show that the p53-related gene p73 is a target of tazarotene. Indeed, tazarotene modulates the expression of the p73 gene in immortalized keratinocyte cell lines by inducing the pro-apoptotic and anti-proliferative TAp73 isoforms and by repressing the anti-apoptotic and pro-proliferative DeltaNp73 isoforms. This occurs at the transcriptional level through a coordinated action on P1p73 and P2p73 promoters that control the expression of TA and DeltaN isoforms, respectively. The selective downregulation of DeltaNp73 expression by small interfering RNA led to an enhancement of tazarotene-induced bax activation and apoptosis, whereas the downregulation of both TA and DeltaN isoforms impairs tazarotene-mediated apoptosis. These results indicate the relevance of p73 gene products in tazarotene-induced growth inhibition and effectiveness in the treatment of skin tumors.

Animals↗

Three-point checklist of dermoscopy. A new screening method for early detection of melanoma.

BACKGROUND: Dermoscopy used by experts has been demonstrated to improve the diagnostic accuracy for melanoma. However, little is known about the diagnostic validity of dermoscopy when used by nonexperts. OBJECTIVE: To evaluate the diagnostic performance of nonexperts using a new 3-point checklist based on a simplified dermoscopic pattern analysis. METHODS: Clinical and dermoscopic images of 231 clinically equivocal and histopathologically proven pigmented skin lesions were examined by 6 nonexperts and 1 expert in dermoscopy. For each lesion the nonexperts assessed 3 dermoscopic criteria (asymmetry, atypical network and blue-white structures) constituting the 3-point method. In addition, all examiners made an overall diagnosis by using standard pattern analysis of dermoscopy. RESULTS: Asymmetry, atypical network and blue-white structures were shown to be reproducible dermoscopic criteria, with a kappa value ranging from 0.52 to 0.55. When making the overall diagnosis, the expert had 89.6% sensitivity for malignant lesions (tested on 68 melanomas and 9 pigmented basal cell carcinomas), compared to 69.7% sensitivity achieved by the nonexperts. Remarkably, the sensitivity of the nonexperts using the 3-point checklist reached 96.3%. The specificity of the expert using overall diagnosis was 94.2% compared to 82.8 and 32.8% achieved by the nonexperts using overall diagnosis and 3-point checklist, respectively. CONCLUSION: The 3-point checklist is a valid and reproducible dermoscopic algorithm with high sensitivity for the diagnosis of melanoma in the hands of non-experts. Thus it may be applied as a screening procedure for the early detection of melanoma.

Adult↗

Diagnosis and categorization of acral melanocytic lesions using teledermoscopy.

We performed a multicentre study to test the validity of teledermoscopy for diagnosing acral melanoma and to evaluate inter-observer agreement on the classification of acral melanocytic lesions. Dermoscopic images of 77 acral melanocytic lesions (71 common melanocytic naevi and 6 melanomas) were sent by email to 11 dermatologists with different degrees of experience in dermoscopy. The observers analysed the images on a computer monitor to diagnose acral melanoma or atypical lesions and to categorize all lesions. All 11 observers, regardless of their degree of experience, obtained high values for sensitivity (mean 0.91, SD 0.09) and specificity (mean 0.95, SD 0.04) with regard to the diagnosis of melanoma. The inter-observer agreement was good to excellent (kappa 0.49-0.88) for the categorization of acral melanocytic lesions. All six melanomas were correctly classified as 'atypical pattern' and all observers recommended surgical excision. Teledermoscopy represents a useful tool for the diagnosis of acral melanoma and for the categorization of patterns that suggest benign or potentially malignant acral melanocytic lesions.

Adolescent↗

Molecular basis of basal cell carcinoma: analysis of differential gene expression by differential display PCR and expression array.

Basal cell carcinoma (BCC) is the most common tumor in the Caucasian population. Although BCC rarely metastasize and cause death, they are problematic due to their destructive growth and the frequent localization on the face. Until now the knowledge of genes differentially expressed in BCC has been incomplete. To elucidate the complex alterations in BCC-associated gene expression, we took advantage of 2 techniques: the differential display RT-PCR (DD-PCR) and the differential hybridization of cDNA arrays. Using DD-PCR, we showed differential expression of genes known from other biological contexts (e.g., rac, ubiquitin hydrolase), which could now be associated with BCC. In addition, we detected unknown genes possibly contributing to the carcinogenesis of BCC. Of the 588 genes screened by differential hybridization of the Atlas human cDNA array, differences in the expression levels of BCC were observed for 10 genes. These data were obtained with RNA probes pooled from several BCC of different donors and were subsequently confirmed by semiquantitative RT-PCR for Janus protein tyrosine kinase 3 (Jak3), microsomal glutathione S-transferase 1 (GST 12), teratocarcinoma-derived growth factor cripto, glutaredoxin and the monocyte chemoattractant protein 1 (MCP-1) in 10 individual BCC specimens, 2 squamous cell carcinoma (SCC), the cell line HaCaT and cultured normal human keratinocytes (NHK) in comparison to normal skin. These genes are candidates from gene families with known association to tumors, but they have not been reported in the carcinogenesis of BCC yet. In summary, both approaches allow the detection of differentially expressed genes possibly involved in the carcinogenesis of BCC.

Basal Cell Carcinoma↗

Cytotoxic/natural killer cell cutaneous lymphomas. Report of EORTC Cutaneous Lymphoma Task Force Workshop.

BACKGROUND: Cutaneous lymphomas expressing a cytotoxic or natural killer (NK) cell phenotype represent a group of lymphoproliferative disorders for which there is currently much confusion and little consensus regarding the best nomenclature and classification. METHODS: This study analyzes 48 cases of primary cutaneous lymphoma expressing cytotoxic proteins and/or the NK cell marker, CD56. These cases were collected for a workshop of the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Task Force, to better clarify the clinical, morphologic, and phenotypic features of these uncommon tumors. RESULTS: Several categories with different clinical and pathologic features were delineated: 1) aggressive, CD8+, epidermotropic, cytotoxic T-cell lymphoma; 2) mycosis fungoides, cytotoxic immunophenotype variant; 3) subcutaneous panniculitis-like T-cell lymphoma; 4) NK/T-cell lymphoma, nasal type; 5) CD4+, NK cell lymphoma; 6) blastoid NK cell lymphoma; (7) intravascular NK-like lymphoma; and 8) cytotoxic, peripheral T-cell lymphoma. CONCLUSIONS: Our data show that primary cutaneous cytotoxic/NK cell lymphomas include distinct groups of diseases, clinically, histologically, and biologically. Because the finding of a cytotoxic phenotype often has prognostic significance, the routine use of cytotoxic markers in the diagnosis and classification of cutaneous lymphomas should be expanded.

CD4-Positive T-Lymphocytes↗

Treatment of toxic epidermal necrolysis with high-dose intravenous immunoglobulins: multicenter retrospective analysis of 48 consecutive cases.

OBJECTIVE: To evaluate the effect of high-dose intravenous immunoglobulin (IVIG) in toxic epidermal necrolysis (TEN), parameters that may affect response to treatment, and the effect of different IVIG batches on Fas-mediated cell death. DESIGN: Multicenter retrospective analysis of 48 consecutive TEN patients treated with IVIG. SETTING: Fourteen university hospital dermatology centers in Europe and the United States. PATIENTS: Forty-eight patients with TEN (skin detachment >10% of their body surface [mean, 44.8%; range, 10%-95%]). INTERVENTIONS: Infusion of IVIG in all patients (range, 0.8-5.8 g/kg), and analysis of the ability of different IVIG batches to inhibit Fas-mediated cell death. MAIN OUTCOME MEASURES: Objective response to IVIG treatment, final outcome at day 45, parameters that may affect response to IVIG treatment, and tolerance. RESULTS: Infusion of IVIG (mean total dose, 2.7 g/kg [range, 0.65-5.8 g/kg]; mean consecutive days, 4 [range, 1-5 days]) was associated with a rapid cessation (mean, 2.3 days [range, 1-6 days]) of skin and mucosal detachment in 43 patients (90%) and survival in 42 (88%). Patients who responded to IVIG had received treatment earlier in the course of disease and, on average, higher doses of IVIG. Furthermore, analysis of 35 IVIG batches revealed significant batch-to-batch variations in the capacity of IVIG to inhibit Fas-mediated cell death in vitro. CONCLUSIONS: Early infusion of high-dose IVIG is safe, well tolerated, and likely to be effective in improving the survival of patients with TEN. We recommend early treatment with IVIG at a total dose of 3 g/kg over 3 consecutive days (1 g/kg per day for 3 days).

Adolescent↗