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Biomedical subjects

B Giannotti

Publications and source records attributed to B Giannotti.

At least 19 recordsLinked to original sources
PubMed2005

Diagnostic and referral accuracy of family doctors in melanoma screening: effect of a short formal training.

Little is known about ability of family doctors in the diagnosis and management (decision as to dermatologic referral) of pigmented skin lesions. We sought to evaluate the impact of a short formal training on diagnostic and referral accuracy of family doctors in melanoma screening. A formal 4-h training session was given to a sample of 41 practising family doctors working in the Florence health district, Tuscany, Italy. Before and after the course, a diagnostic test with a series of clinical images of pigmented skin lesions including four invasive melanomas (mean thickness, 1.5 mm; range, 0.8-2.2) was performed (open intervention study). Although only 46.8% of observations yielded a correct melanoma diagnosis at baseline, 96.1% of melanoma observations were correctly associated with intention to refer the lesion to dermatologist. After training, the percentage of correct melanoma diagnosis significantly increased (76.2%, P=0.01) while no further improvement was found as to sensitivity of referral (94.8%, P=0.58). Compared to baseline, post-training evaluation showed a significant reduction of benign lesions sent to dermatologist: the percentage lowered from 52.1 to 35.8% (P=0.0014) for melanocytic nevi and from 38.6 to 17.5% (P<0.001) for benign non-melanocytic lesions (pigmented seborrheic keratoses, dermatofibromas, and vascular lesions). Grouping these two diagnostic categories, the overall specificity in dermatology referral increased from 55.0% at baseline to 73.1% after training (P<0.001). In conclusion, attendance at a 4-h formal training session was able to increase the specificity of family doctors as to dermatologist referral of suspicious lesions (less false-positive referral of benign lesions) without significant loss in sensitivity concerning melanoma.

Dermatology↗
PubMed2004

Improvement of malignant/benign ratio in excised melanocytic lesions in the 'dermoscopy era': a retrospective study 1997-2001.

BACKGROUND: Because of the many limitations of studies based on the diagnostic setting of excised lesions, the impact of dermoscopy (epiluminescence microscopy, dermatoscopy) in melanoma screening during practice remains to be established. OBJECTIVES: We assumed that effects of the use of dermoscopy on some indicators of diagnostic performance in melanoma screening should be traceable retrospectively; therefore, we analysed the impact of routine dermoscopy use on the malignant/benign ratio in excised melanocytic lesions. METHODS: Preoperative and histological diagnosis of 3053 melanocytic lesions [319 melanomas (10.4%)] consecutively diagnosed and excised at the Department of Dermatology, University of Florence in the period 1997-2001 inclusive were retrieved. Six dermatologists who selected the lesions to excise and who performed preoperative diagnosis were divided into two groups according to their use of dermoscopy in routine activity (n = 2 dermoscopy users and n = 4 nonusers). The study period was divided into a predermoscopy period (1997), a shift phase (1998) and a dermoscopy period (1999-2001). RESULTS: During the study period, the malignant/benign ratio improved in dermoscopy users only (from 1 : 18 to 1 : 4.3, P = 0.037). No significant difference was found for nonusers (from 1 : 11.8 to 1 : 14.4). Dermoscopy users were more likely to have a melanoma diagnosed within a series of excised lesions than nonusers, even taking into account potential confounders such as sex, age and study period by means of multivariate analysis (odds ratio 1.55, 95% confidence interval 1.17-2.01). The percentage of 'problem' naevi (naevi with architectural disorder with or without cytological atypia and Spitz or Reed naevi) over the total number of excised lesions was higher in dermoscopy users than in nonusers (year 2001, 51.6% vs. 40.9%, P = 0.014). Similar findings were obtained after exclusion from the data set of lesions excised for cosmetic reasons. CONCLUSIONS: The adoption of dermoscopy in routine melanoma screening is followed by an improvement of the malignant/benign ratio in excised lesions, suggesting a more appropriate selection of pigmented lesions referred to surgery. Because of the possible limitations of a retrospective study design, future confirmation of this finding by means of a prospective, randomized study is advisable. The introduction of dermoscopy in routine practice may have major implications in large-scale melanoma screening with cost savings and a reduction of the dermosurgery workload.

Female↗
PubMed2004

Self-detected cutaneous melanomas in Italian patients.

Self-detection of suspicious pigmented skin lesion combined with rapid referral to dermatologic centres is the key strategy in the fight against melanoma. The investigation of factors associated with pattern of detection of melanoma (self- vs. nonself-detection) may be useful to refine educational strategies for the future. We investigated the frequency of melanoma self-detection in a Mediterranean population at intermediate melanoma risk. A multicentric survey identified 816 consecutive cases of cutaneous melanoma in the period January to December 2001 in 11 Italian clinical centres belonging to the Italian Multidisciplinary Group on Melanoma. All patients filled a standardized questionnaire and were clinically examined by expert dermatologists. Self-detected melanomas were 40.6%, while the remaining lesions were detected by a dermatologist (18.5%), the family physician (15.2%), other specialists (5%), the spouse (12.5%), a friend or someone else (8.2%). Variables associated with self-detected melanomas were female sex, young age, absence of atypical nevi, knowledge of the ABCD rule, habit of performing skin self-examination. Self-detected melanomas did not differ from nonself-detected tumours in term of lesion thickness; however, patients with self-detected melanomas waited a longer period before having a diagnostic confirmation (patient's delay) (> 3 months: odds ratio, 3.89; 95% confidence interval, 2.74-5.53). In order to reduce the patients' delays, educational messages should adequately stress the need for a prompt referral to a physician once a suspicious pigmented lesion is self-detected.

Adult↗
PubMed2003

BCA-1, A B-cell chemoattractant signal, is constantly expressed in cutaneous lymphoproliferative B-cell disorders.

We analysed the immunophenotypic and molecular expression of BCA-1 (B-cell-specific chemokine) and CXCR5 (BCA-1 receptor) in normal skin and different cutaneous lymphoproliferative disorders (cutaneous T-cell lymphoma (CTCL); cutaneous B-cell lymphoma (CBCL); cutaneous B-cell pseudolymphoma (PCBCL)), with the aim of investigating their possible involvement in the pathogenesis of cutaneous B-cell disorders. BCA-1 and CXCR5 were constantly expressed in CBCL and PCBCL, but not in normal skin and CTCL. BCA-1 and CXCR5 were constantly coexpressed by CD22+ B-cells, while CD35+ follicular dendritic cells coexpressed BCA-1 in PCBCL cells only. In low grade CBCL, as compared with high grade CBCL, the intensity of CXCR5 expression on neoplastic CD22+ cells was lower than that of BCA-1. The image analysis of reverse transcriptase-polymerase chain reaction (RT-PCR) products showed a significant quantitative difference between PCBCL/low grade CBCL and high grade CBCL. The above findings, although only observed in a small series of patients, are in keeping with findings in MALT gastric and gastric MALT lymphomas, adding further evidence of the close similarities between CBCL and MALT lymphomas.

Base Sequence↗
PubMed2003

The treatment of basal cell carcinomas in a patient with xeroderma pigmentosum with a combination of imiquimod 5% cream and oral acitretin.

Xeroderma pigmentosum (XP) is a rare autosomal recessive photosensitive disorder, which results in multiple face, neck and head basal cell carcinomas (BCCs), squamous cell carcinomas and melanomas. A 15-year-old boy with XP presented with multiple facial BCCs previously treated by surgical excision. Standard BCC treatments such as surgery are not ideal for patients with several facial BCCs because of the risk of scarring, and the patient refused further surgery. As an alternative, three times weekly application of imiquimod 5% cream in combination with oral acitretin (20 mg daily) was prescribed for 4-6 weeks. No adverse events were reported during treatment and all tumours had resolved at the 6-month follow up visit, highlighting the therapeutic potential of imiquimod 5% cream.

Acitretin↗
PubMed2003

Cutaneous melanoma in the Florentine area, Italy: incidence, survival and mortality between 1985 and 1994.

In recent decades, the increase in incidence of melanoma (MM) and the consequent mortality pointed to the concept of a 'melanoma epidemic'. More recently, the mortality has been slowly declining in many countries. This study is aimed at evaluating the incidence, mortality and survival in the Florentine area of Italy, using registry-based information. Between 1985 and 1994, 997 cases were notified with a survival of 713 patients (1985-92) and 316 deaths. Age-adjusted incidence, mortality rates and 95% confidence interval were calculated by period, gender and Breslow thickness. The relative survival rates were calculated and the effects of prognostic factors were evaluated using multivariate analysis. The incidence of MM increased during this period. This result referred only to 'thin melanomas', while the incidence rate for melanomas thicker than 1.00 mm remained unchanged both in young and old individuals. The mortality rate remained stable. The 5-year survival rate increased between 1985 and 1992. The inclusion of Breslow thickness in the multivariate model caused a reduction of the period effect. In conclusion, a changing pattern of MM epidemiology is being observed, with increase of 'thin' forms and a tendency for mortality to decline. The increasing awareness of population about MM prevention may partially explain these findings.

Adult↗
PubMed2002

Immunophenotypical markers, ultrastructure and chemosensitivity profile of metastatic melanoma cells.

The survival of patients affected by cutaneous melanoma has improved dramatically in the last 10 years, because of earlier diagnosis. Despite this, the therapeutic results obtained in metastatic melanoma (MM) are very disappointing due to its poor responsiveness to cytotoxic agents. In this type of solid tumor, tumor chemosensitivity assays have been suggested to be an important tool to predict clinical responsiveness to therapy. Metastatic melanoma cells (MMCs) were obtained from subcutaneous melanoma metastases of five patients and cultured for several consecutive passages. An immunofluorescence and an electron microscopic study were performed in order to establish the ultrastructural and physiopathological features of MMCs. A sulphorodamine-B test was used to measure in vitro sensitivity of MMCs to temozolomide, cisplatin, vindesine, taxol and interpheron alpha-2a. Following a 72 h exposure, maximum activity was obtained with vindesine (median inhibitory concentration, IC(50), 0.23 nM) and taxol (median IC(50) 0.31 nM). Cisplatin median IC(50) values were higher (4.6 microM) than taxol and vindesine, but still in the range of clinically achievable plasma concentrations. Temozolomide inhibited cell proliferation only at very high concentrations (median IC(50) 228 microM). No significant cell growth inhibitory effects (<or=25%) were observed with interferon alpha-2a concentrations up to 8000 IU/ml. MMCs expressed progression markers typical of cutaneous metastatic melanoma and showed poor sensitivity in vitro to most anticancer drugs tested, including temozolomide.

Antineoplastic Agents↗
PubMed2002

Modern diagnosis of cutaneous lymphoma.

The issue of primary cutaneous lymphoma (CL) has been greatly influenced by the increasing knowledge about lymphoid cell biology, the widespread use of sensitive and specific immunological and molecular markers, and the careful correlation among clinical, histological and immunomolecular features. This latter is the key element of the classification of CL proposed by the EORTC Cutaneous Lymphoma Study Group in 1997, which categorizes distinct clinicopathological entities with prognostic and therapeutic relevance. With few exceptions, no reliable diagnosis and subtyping of CL can be made without the aid of immunohistochemistry and/or molecular analysis. On the other hand, the acritical use of immunological and molecular markers can be misleading if not combined properly with a correct clinical and histological evaluation. For this reason, a step-by-step diagnosis and staging protocol is exceedingly important. Finally, great caution should be used in the interpretation of lymphoid cell infiltrates of the skin which show a monoclonal rearrangement in the absence of reliable clinical and/or pathological evidence of neoplasia.

Humans↗
PubMed2002

Melanoma detection rate and concordance between self-skin examination and clinical evaluation in patients attending a pigmented lesion clinic in Italy.

BACKGROUND: The early diagnosis of melanoma is based on the collaboration between dermatologists and family doctors, who filter subjects to be referred to a pigmented lesion clinic (PLC). Following growing media coverage, there is increasing concern in the general population about the risk of the 'changing mole', resulting in a progressively increased workload in PLCs. AIM AND METHODS: We investigated the causes of referral to a PLC in a series of 193 attendees seen consecutively at the PLC of the University of Florence. Because the number of naevi is the major risk factor for melanoma in Mediterranean populations, the concordance between self-counting of naevi and the clinical evaluation of a PLC dermatologist in order to classify high-risk individuals was also investigated. RESULTS: Detection of a clinically suspicious lesion at dermatological examination occurred in 13 of 193 subjects referred by general practitioners (6.7%), with three melanomas confirmed histologically (overall detection rate: three of 193, 1.6%). The positive predictive value of the 'presence of a suspicious lesion', the cause of referral in 39.9% of subjects, was 9.1% when based on the gold standard criterion represented by the clinical detection of a suspicious lesion by the dermatologist and 3.8% based on the histological diagnosis of melanoma; the negative predictive value was 94.8% (100% when based on the histological diagnosis of melanoma), suggesting that the clinical detection of a suspicious lesion in subjects with different causes of referral (such as risk factors for melanoma, or the need to be reassured about moles) is unlikely. There was poor agreement between self-evaluation based on the presence of multiple naevi and the dermatological examination (gold standard) for both common and atypical naevi. The highest concordance (kappa = 0.32, 95% confidence interval 0.20-0.43) was associated with a dichotomized count of naevi as up to 50 or more than 50 naevi. CONCLUSIONS: In order to reduce the PLC workload, the filtering role of the family doctor needs to be improved, so that only subjects with a specific suspicious lesion are referred to the PLC. The self-assessment of melanoma risk based on the presence of multiple naevi was not reliable.

Adolescent↗
PubMed2002

Pre-operative diagnosis of pigmented skin lesions: in vivo dermoscopy performs better than dermoscopy on photographic images.

BACKGROUND: Epiluminescence microscopy (ELM) (dermoscopy, dermatoscopy) is a technique for non-invasive diagnosis of pigmented skin lesions that improves the diagnostic performance of dermatologists. Little is known about the possible influence of associated clinical features on the reliability of dermoscopic diagnosis during in vivo examination. OBJECTIVE: To compare diagnostic performance of in vivo dermoscopy (combined clinical and dermoscopic examination) with that of dermoscopy performed on photographic slides (pure dermoscopy). DESIGN: This case series comprised 256 pigmented skin lesions consecutively identified as suspicious or equivocal during examination in a general dermatological clinic. Clinical examination and in vivo dermoscopy were performed before excision by two trained dermatologists. The same observers carried out dermoscopy on photographic slides at a later time, and these three diagnostic classifications were reviewed together with the histological findings for the individual lesions. This was carried out in a university hospital. RESULTS: In vivo dermoscopy performed better than dermoscopy on photographic slides for classification of pigmented skin lesions compared with histological diagnosis, and both performed better than general clinical diagnosis. In vivo dermoscopic diagnosis of melanoma showed 98.1% sensitivity, 95.5% specificity and 96.1% diagnostic accuracy while dermoscopic diagnosis of melanoma on photographic slides was less reliable with 81.5% sensitivity, 86.7% specificity and 85.2% diagnostic accuracy. In particular, diagnosis of melanoma based on photographic slides led to nine false negative cases (three in situ, six invasive; thickness ranges 0.2-1.5 mm). CONCLUSIONS: In vivo dermoscopy, i.e. combined clinical and dermoscopic examination, is more reliable than dermoscopy on photographic slides. In clinical practice, therefore, in vivo dermoscopy cannot be considered independent from associated clinical characteristics of the lesions, which help the trained observer to reach a more precise classification. This may have implications on the reliability of ELM diagnosis made by an observer not fully trained in the clinical diagnosis of pigmented skin lesions or by a remote observer during digital ELM teleconsultation.

Adult↗
PubMed2001

Dermoscopy as a second step in the diagnosis of doubtful pigmented skin lesions: how great is the risk of missing a melanoma?

BACKGROUND: Little is known about the occurrence of false negatives in the diagnosis of melanoma using dermoscopy in clinical practice: in the literature dermoscopy only increased the accuracy of diagnosis of equivocal lesions that were to undergo biopsy anyway. AIM AND METHODS: We collected the 81 lesions clinically diagnosed as probable melanomas by experienced specialists (from a series of 256 pigmented skin lesions submitted to excisional biopsy) and reviewed them for possible false negative results in the diagnosis of melanoma using in vivo dermoscopy and dermoscopy performed on slide images. Both procedures were carried out by the same experienced dermatologists who classified the lesions clinically. RESULTS: Dermoscopy made on slide images (observers blinded for clinical features of the lesions) yielded three false negative results (91% sensitivity) in a group of 35 histologically confirmed melanomas. In vivo dermoscopy showed better results, with no melanomas missed (100% sensitivity). The frequency of false positive results in the diagnosis of melanoma was 13.5% (11 of 81) with dermoscopy on slide images and 2.5% (two of 81) with in vivo dermoscopy. CONCLUSIONS: Only in vivo dermoscopy by fully trained dermatologists with both clinical and dermoscopic experience avoids the risk of misclassification of melanomas otherwise correctly classified on clinical grounds.

Dermatology↗
PubMed2001

Control of the differentiation state and function of human epidermal Langerhans cells by cytokines in vitro.

Langerhans cells can originate in vitro from immature precursors stimulated with granulocyte macrophage-colony-stimulating factor (GM-CSF), tumour necrosis factor (TNF)-alpha and stem cell factor (SCF). We asked whether these cytokines also control the differentiation state of Langerhans cells within the epidermis and upon leaving this tissue. We harvested sheets of human epidermis by controlled dispase hydrolysis of keratomes, cultured them in RPMI and 10% fetal calf serum for 48 h and analysed the sheets and the cells migrated spontaneously into the medium, most of which were Langerhans cells containing Birbeck granules. By flow cytometry, the intensity of CD1a expression was reduced quite evenly among Langerhans cells migrated from sheets within 48 h. The cells in the sheets underwent loss of dendrites, with a significant reduction in the cell perimeter that was prevented by GM-CSF and TNF-alpha together. Either of these cytokines induced expression of CD18 by cells in the sheets and those in the medium. Moreover, TNF-alpha induced expression of CD54 by cells in the medium, but not by those retained in the sheets, whereas human SCF induced, dose dependently, expression of CD54 by cells in the sheets, but not from those in the medium. The proliferation of allogeneic lymphocytes was much higher when stimulating Langerhans cells were harvested from cultures with any cytokine, rather than from cultures without cytokines. We conclude the following: (i) GM-CSF and TNF-alpha help to maintain full differentiation of Langerhans cells within the epidermis; (ii) cytokine influence on Langerhans cells adhesiveness is in part context dependent; and (iii) pretreatment with cytokines influences positively the number or accessory activity of Langerhans cells on lymphocytes during subsequent mixed leucocyte reaction.

Cell Differentiation↗
PubMed2001

Non-invasive analysis of melanoma thickness by means of dermoscopy: a retrospective study.

Epiluminescence microscopy (ELM), or dermatoscopy, is a non-invasive technique for the diagnosis of cutaneous melanoma that may play a role in the non-invasive, preoperative assessment of melanoma thickness. This study investigated the correlation between the frequency of appearance of some standard ELM criteria and the histological thickness of melanomas. In addition, the possible role of the total dermoscopic score (TDS) according to ABCD rule of dermoscopy as a predictor of melanoma thickness was analysed. The dermoscopic images of 84 cutaneous melanomas were retrospectively investigated to evaluate the presence of 10 standard ELM criteria, and for each lesion the TDS was established (with observers blinded as to the tumour thickness). A statistically significant association was found between the presence of an irregular pigment network and melanomas with a Breslow index equal to or lower than 0.75 mm (positive predictive value of 68%); in contrast, radial streaming, atypical vascular pattern and grey-blue areas were associated with melanomas > 0.75 mm (positive predictive values of 77%, 65% and 70%, respectively). Of the melanomas thinner than 0.76 mm, 82% showed a TDS lower than 6.80 (optimized cut-off point), while 79% of melanomas thicker than 0.75 mm had a TDS higher than 6.80 (chi2 = 30.815, P < 0.001); the positive predictive value of a TDS > 6.80 in the detection of lesions thicker than 0.75 mm was 79%. In conclusion, a statistically significant correlation does exist between some dermoscopic features and melanoma thickness. Both the mostly used dermoscopic methods (standard ELM pattern analysis and the ABCD rule of dermatoscopy) may provide useful information in the non-invasive assessment of melanoma thickness. However, their diagnostic performance is far from 100%; further studies are needed to investigate whether the combination of dermoscopy with other non-invasive approaches (e.g. sonometry) may result in an overall improvement in the diagnostic performance.

Adolescent↗