Publications by authors named "Giovanni Pellacani"

354 Publications

Fluorescent light energy combined with systemic isotretinoin: A 52-week follow-up evaluating efficacy and safety in treatment of moderate-severe acne.

Clin Case Rep 2021 Apr 20;9(4):2057-2068. Epub 2021 Feb 20.

Klox Technologies Europe Dublin Ireland.

Fluorescent light energy therapy combined with low-dose isotretinoin or tetracycline show remarkable clinical effect on 12 cases of moderate-to-severe acne. Treatment was considered safe, well-tolerated, and highly efficacious.
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http://dx.doi.org/10.1002/ccr3.3944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077247PMC
April 2021

New systemic therapies for cutaneous melanoma: why, who and what.

Ital J Dermatol Venerol 2021 Apr 29. Epub 2021 Apr 29.

Centro Oncologico ad Alta Tecnologia Diagnostica, Azienda Unità Sanitaria Locale, IRCCS di Reggio Emilia, Reggio Emilia, Italy -

Incidence of melanoma has been increasing in both sexes in the last decades. Advanced melanoma has always been one of the deadliest cancer worldwide due to his high metastatic capacity. In the last ten years, progresses in the knowledge of the molecular mechanisms involved in the melanoma development and progression, and in immune-response against melanoma, empowered the development of two new classes of systemic therapeutic agents: target-therapies and immunotherapies. Both of these classes consist of monoclonal antibodies inhibiting specific molecules. Target-therapies are selectively directed against cells harbouring the BRAFV600-mutation, while immunotherapies target the two molecules involved in immune-checkpoint regulation, enhancing the immune response against the tumor: cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 receptor (PD-1). Target- and immunotherapy demonstrated to improve both progression-free and overall survival in melanoma patients either in metastatic or in adjuvant settings. Several drugs have been approved in recent years as monotherapy or in combination, and many other drugs are currently under investigation in clinical trials. In the current review on new systemic therapies for cutaneous melanoma, we revise the molecular basis and the mechanisms of actions of both target- and immunotherapy (why). We discuss who are the best candidate to receive such therapies in both the adjuvant and metastatic setting (who) and which are the most important efficacy and safety data on these drugs (what).
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http://dx.doi.org/10.23736/S2784-8671.21.06936-4DOI Listing
April 2021

A Validated Photonumeric Scale for the Evaluation of Neck Skin Laxity.

Dermatol Surg 2021 May;47(5):e188-e190

All authors are affiliated with the Dermatology Unit, Department of Surgical, Medical, Dental and Morphological Science with Interest Transplant, Oncological and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy.

Background: Neck aging is usually evaluated together with the lower face. To date, a skin laxity scale for the neck as an independent anatomical district is lacking.

Objective: To create and validate a proposed photonumeric neck skin laxity (NSL) scale.

Materials And Methods: Frontal neck photographic images of 110 subjects were collected. Each standardized neck image was evaluated twice by 3 independent doctors, 1 week apart. A 4-point photonumeric NSL scale was developed (0 = absence of skin laxity and 4 = severe skin laxity) and validated in terms of intraobserver and interobserver correlation and internal consistency.

Results: The intraobserver reliability analysis of the 2 assessments performed by each observer revealed excellent correlation and consistency of the severity grading, independently of the time of evaluation (from 0.96 to 0.99, p < .01). Furthermore, the interobserver reliability analysis revealed an excellent agreement between the evaluators and an internal consistency independent of the evaluator (0.97, p < .01).

Conclusion: The newly developed NSL scale is a reliable and reproducible scoring system for the aesthetic evaluation of skin laxity of the neck.
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http://dx.doi.org/10.1097/DSS.0000000000002865DOI Listing
May 2021

Thumb up for a false alarm!

Ital J Dermatol Venerol 2021 Apr 23. Epub 2021 Apr 23.

Centro Oncologico ad Alta Tecnologia Diagnostica-Dermatologia, Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Reggio Emilia, Italy.

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http://dx.doi.org/10.23736/S2784-8671.21.06847-4DOI Listing
April 2021

A plea for standardization of confocal microscopy and optical coherence tomography parameters to evaluate physiological and para-physiological skin conditions in cosmetic science.

Exp Dermatol 2021 Apr 21. Epub 2021 Apr 21.

Dermatology Unit, University of Modena and Reggio Emilia, Modena, Italy.

Background: Non-invasive Reflectance Confocal Microscopy (RCM) and Optical Coherence Tomography (OCT) have been extended to the dermo-cosmetic field, for skin pathophysiology understanding and therapeutics monitoring. However, standardized methodology and parameters to interpret structures and changes in these settings are still lacking.

Objective: to propose a validated standard methodology and a list of defined parameters for objective non-pathological skin assessments in the cosmetically sensitive cheekbone area of the face.

Methods: OCT and RCM quantitative, semi-quantitative, and qualitative features were considered for assessments. Validation process included 50 sets of images divided into 2 age groups. Inter-rater reliability was explored to assess the influence of the proposed methodology.

Results: Quantitative OCT parameters of "epidermal thickness", "density and attenuation coefficients" and "vascular density" were considered and calculated. Severity scales were developed for semi-quantitative OCT features of "disruption of collagen" and "vascular asset", while extent-scales were produced for semi-quantitative RCM "irregular honeycomb", "mottled pigmentation" and "polycyclic papillary contours". Qualitative assessment was obtained for RCM type of collagen and comparison between age-groups was performed for all features considered. Severity visual scales assistance proved excellent inter-rater agreement across all semi-quantitative and qualitative domains.

Conclusions: The assistance of shareable software systems allows for objective OCT quantitative parameters measurement. The use of standard reference scales, within a defined assessment methodology, offers high inter-rater reliability, and thus reproducibility for semi-quantitative and qualitative OCT and RCM parameters. Taken together, our results may represent a starting point for a standardized application of RCM and OCT in dermo-cosmetic research and practice.
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http://dx.doi.org/10.1111/exd.14359DOI Listing
April 2021

Current and future perspectives of digital microscopy with fluorescence confocal microscope for prostate tissue interpretation: a narrative review.

Transl Androl Urol 2021 Mar;10(3):1569-1580

Department of Urology, University of Modena and Reggio Emilia, Modena, Italy.

Fluorescence confocal microscopy (FCM) is an optical imaging technique providing digital microscopical images of fresh tissue in a real time fashion, without conventional processing. FCM has been widely applied in several fields of dermatology, including the detection of basal cell carcinoma and of cutaneous inflammatory diseases. The aim of the paper is to provide an overview of FCM applications in the field of prostate tissue interpretation and prostate cancer (PCa) detection. A Literature search (PubMed & Web of Science) was performed to identify articles concerned with the clinical and surgical applications of FCM in prostatic and periprostatic tissues interpretation. Overall, six articles were identified. All articles investigated the level of agreement between FCM and conventional histopathological analysis (hematoxylin-eosin, HE) for the discrimination between normal and PCa tissues. An investigative article on prostate samples retrieved from radical prostatectomy (RP) specimens and an atlas of FCM digital images from the same series were found. Two prospective clinical trials, comparing FCM and HE, pointed out a "substantial" to "almost perfect" discriminative performance of FCM for the diagnosis of PCa on prostate biopsy core. Finally, two studies investigated the intra-operative role of FCM during RP for the control of surgical dissection. In this setting, FCM could be used to analyse samples retrieved from suspicious peri-prostatic areas; FCM has also been tested for an en-face evaluation of flat slices obtained from the systematic sampling of the posterolateral aspects of the prostate, in a NeuroSAFE-like approach. Generally, FCM provides digital microscopical images of fresh tissue in a real time fashion, without requiring conventional processing. Currently, available studies confirmed a high concordance with conventional pathology for the detection of PCa. Further studies are required to validate the technology, to evaluate ISUP score attribution and to implement the fields of application of FCM for the treatment of prostate diseases.
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http://dx.doi.org/10.21037/tau-20-1237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039586PMC
March 2021

Melasma treatment: a systematic review.

J Dermatolog Treat 2021 Apr 14:1-39. Epub 2021 Apr 14.

Plastic and Reconstructive Surgery Unit, Campus Bio-Medico University of Rome, Rome, Italy.

Melasma is a common chronic refractory disorder of pigmentation affecting people with darker skin types. Overall prevalence varies between 8.8% and 40%, depending on the ethnicity of the population and the geographical area. Therapeutic management of melasma is challenging, with high recurrence rates which significant impacts on the quality of life. No single treatment is universally efficacious. Systemic treatments with tranexamic acid and polypodium leucotmatous had promising results, although the former was related to systemic side effects. Microneedling and peeling were also efficacious, although their superiority to topical hydroquinone, the gold standard in melasma treatment, remains to be established. Similarly, laser and light devices have been beneficial. However, recurrence rates remain high in all treatment groups. Combination therapies, either in double or triple combinations yielded the best results when compared to single terapies. Treatment choice should be made after Wood's lamp examination, as well as dermatoscopic evaluation, in order to select the best treatment option, targeted at each melasma subtype.
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http://dx.doi.org/10.1080/09546634.2021.1914313DOI Listing
April 2021

Dynamic dermoscopic and reflectance confocal microscopic changes of melanocytic lesions excised during follow-up.

J Am Acad Dermatol 2021 Apr 3. Epub 2021 Apr 3.

Dermatology Unit, Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant, Oncological and Regenerative Medicine, University of Modena and Reggio Emilia, Via del Pozzo 71, 41125, Modena, Italy; Dermatology Clinic, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, La Sapienza University of Rome, Italy.

Background: Digital dermoscopy follow-up (DDF) is useful in improving melanoma recognition, catching early changes over time, although benign nevi can also show changes. Reflectance confocal microscopy (RCM) improves melanoma diagnostic accuracy and decreases the number of unnecessary resections.

Objectives: To evaluate dynamic dermoscopic and RCM changes during follow-up of equivocal melanocytic lesions and assess the impact of adjunctive RCM to DDF for melanoma diagnosis.

Methods: A retrospective, multicenter study of extra-facial atypical melanocytic lesions excised during follow-up was performed. Morphological changes were evaluated comparing dermoscopy and RCM baseline and follow-up images.

Results: 137 atypical melanocytic lesions were studied, including 14 melanomas and 123 benign nevi. Significantly greater changes in DDF of atypical network, regression, atypical streaks and asymmetrical growth and in dynamic RCM of atypical cells and dermal-epidermal junction (DEJ) disarray were note in melanomas. With adjunctive dynamic RCM and major changes at DDF, sensitivity reached 100% with 40.6% specificity.

Limitations: Selected series of "difficult to recognize" lesions, with both DDF and dynamic RCM images.

Conclusion: Adjunctive dynamic RCM improves early melanoma recognition sensitivity.
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http://dx.doi.org/10.1016/j.jaad.2021.03.081DOI Listing
April 2021

Dermoscopy of early melanomas: variation according to the anatomic site.

Arch Dermatol Res 2021 Mar 26. Epub 2021 Mar 26.

Dermatology Unit, Department of Medical, Surgical and Neurosciences, University of Siena, Siena, Italy.

To date, is yet to be elucidated whether the body location of cutaneous melanoma can significantly affect an early dermoscopic diagnosis and, consequently, if it can be regarded as a prognostic factor. To investigate the dermoscopic appearance of early melanomas (EMs) at different body sites; to test the ability of dermoscopists in recognizing specific dermoscopic features in EMs. A pool of 106 experienced dermoscopists evaluated the presence of 10 dermoscopic features assumed as suggestive of malignancy among 268 images of EMs with ambiguous appearance located at 16 body sites. According to 720 evaluations, EMs of the "upper extremities" showed a prevalence of early atypical lentiginous features. EMs of the "anterior trunk" exhibited the lower rate of recognition for all features. EMs of the "rear trunk" can be regarded as an intermediate area, showing high recognition rates of regression-related and chronic-traumatism-related features.
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http://dx.doi.org/10.1007/s00403-021-02226-xDOI Listing
March 2021

Circulating mucosal-associated invariant T cells identify patients responding to anti-PD-1 therapy.

Nat Commun 2021 03 15;12(1):1669. Epub 2021 Mar 15.

Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy.

Immune checkpoint inhibitors are used for treating patients with metastatic melanoma. Since the response to treatment is variable, biomarkers are urgently needed to identify patients who may benefit from such therapy. Here, we combine single-cell RNA-sequencing and multiparameter flow cytometry to assess changes in circulating CD8 T cells in 28 patients with metastatic melanoma starting anti-PD-1 therapy, followed for 6 months: 17 responded to therapy, whilst 11 did not. Proportions of activated and proliferating CD8 T cells and of mucosal-associated invariant T (MAIT) cells are significantly higher in responders, prior to and throughout therapy duration. MAIT cells from responders express higher level of CXCR4 and produce more granzyme B. In silico analysis support MAIT presence in the tumor microenvironment. Finally, patients with >1.7% of MAIT among peripheral CD8 population show a better response to treatment. Our results thus suggest that MAIT cells may be considered a biomarker for patients responding to anti-PD-1 therapy.
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http://dx.doi.org/10.1038/s41467-021-21928-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961017PMC
March 2021

Clinical and Dermoscopic Factors for the Identification of Aggressive Histologic Subtypes of Basal Cell Carcinoma.

Front Oncol 2020 19;10:630458. Epub 2021 Feb 19.

Centro Oncologico ad Alta Tecnologia Diagnostica, Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Reggio Emilia, Italy.

Background: Infiltrative basal cell carcinoma (BCC) has a higher risk for post-surgical recurrence as compared to the most common low-aggressive superficial and nodular BCC. Independent diagnostic criteria for infiltrative BCC diagnosis have not been still defined. Improving the pre-surgical recognition of infiltrative BCC might significantly reduce the risk of incomplete excision and recurrence.

Objective: The aim of this study is to define clinical and dermoscopic criteria that can differentiate infiltrative BCC from the most common low-aggressive superficial and nodular BCC.

Methods: Clinical and dermoscopic images of infiltrative, superficial, and nodular BCC were retrospectively retrieved from our database and jointly evaluated by two experienced dermoscopists, blinded for the histologic subtype. Pairwise comparisons between the three histologic subtypes were performed and multivariable logistic regression models were constructed in order to define clinical and dermoscopic factors independently associated with each subtype. To validate our findings, two experienced dermoscopists not previously involved in the study were asked to evaluate clinical and dermoscopic images from an external dataset, guessing the proper BCC subtype between infiltrative, nodular and superficial, before and after being provided with the study results.

Result: A total of 481 histopathologically proven BCCs (51.4% nodular, 33.9% superficial, and 14.8% infiltrative) were included. We found that infiltrative BCC mostly appeared on the head and neck as an amelanotic hypopigmented plaque or papule, displaying ulceration on dermoscopic examination, along with arborizing and fine superficial telangiectasia. Shiny white structures were also frequently observed. Multivariate regression analysis allowed us to define a clinical-dermoscopic profile of infiltrative BCC.

Conclusions: We defined the clinical-dermoscopic profile of infiltrative BCC, allowing to differentiate this variant from superficial and nodular BCC. This will improve pre-surgical recognition of infiltrative forms, reducing the risk for post-surgical recurrence.
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http://dx.doi.org/10.3389/fonc.2020.630458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933517PMC
February 2021

Orofacial Granulomatosis: Clinical and Therapeutic Features in an Italian Cohort And Review of the Literature.

Allergy 2021 Feb 28. Epub 2021 Feb 28.

Center for Basic and Clinical Immunology Research (CISI), WAO Center of Excellence, Department of Translational Medical Sciences, Allergy and Clinical Immunology, University of Naples Federico II, Naples, Italy.

Background: Orofacial granulomatosis (OFG) is characterized by granulomatous inflammation of the soft tissues of maxillofacial region. We explored OFG patients from 10different Italian Centers and summarized the most recent literature data.

Methods: a review ofpatients with OFG was carried out. An extensive online literature search was performed to identify studies reporting diagnosis and management of OFG.

Results: Thirty-nine patients were recruited between January 2018 and February 2020. Most of them (97.4%) displayed involvement of the lipsand 28.2% suffered from Melkersson-Rosenthal Syndrome. Two patients received diagnosis of CD and one patient of sarcoidosis, suggesting secondary OFG.Oral aphthosis and cervical lymphadenopathy were also described.The mean diagnostic delay was 3.4 years.Histological evaluation was performed in 34/39 patients (87.2%); non-caseating granulomas were found in 73.5% of them.Neurological symptoms (28.2%), gastrointestinal symptoms in absence of overt inflammatory bowel disease (IBD) (20.5%) and atopy (35.9%) were also identified. Therapeutic approaches varied among the centers. Steroids (51.3%) were used with good or partial results.Anti-TNF-α and anti-IgE monoclonal antibodieswere used in 6(15.4%) and 1(2.6%) patients, respectively, with variable results. Surgery was the choice for 2 patients with good response.

Conclusions: OFG is a rare and neglected disease showing multiple clinical phenotypes. While early diagnosis is crucial,managementis difficult and highly dependent on the expertise of clinicians due to the lack of international guidelines. There is a need to establishregistry databases and address challenges of long-term management.
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http://dx.doi.org/10.1111/all.14799DOI Listing
February 2021

A Novel Multi-Action Emollient Plus Cream Improves Skin Barrier Function in Patients with Atopic Dermatitis: In vitro and Clinical Evidence.

Skin Pharmacol Physiol 2021 18;34(1):8-18. Epub 2021 Feb 18.

Department of Surgical, Medical, Dental, and Morphological Sciences, Dermolab, University of Modena and Reggio Emilia, Modena, Italy.

Background: Emollients capable of restoring the skin barrier function would extend their role beyond basic maintenance therapy in atopic dermatitis (AD).

Objectives: Investigate the effect of a novel emollient plus cream (EC; Dermoflan®) on the skin barrier in vitro and in patients with mild-to-moderate AD.

Methods: The effect of EC on the skin barrier recovery was evaluated using a tape-stripping (TS) model. After TS, organ cultures were treated with EC (undiluted or diluted 1:1 with water) and analyzed at 18-120 h using hematoxylin and eosin, Oil Red O, immunohistochemical, and immunofluorescent techniques. In a double-blind, randomized study, EC or placebo was applied once daily for 2 months to antecubital folds of the upper and lower limbs of patients with mild-to-moderate AD in clinical remission. Epidermal thickness, vascularization, and epidermal hydration were assessed by optical coherence tomography and corneometry, respectively, at baseline, and 1 and 2 months following treatment initiation.

Results: Following TS, EC treatment significantly increased epidermal thickness and lipid content versus diluent in the skin organ culture, as well as claudin-1, involucrin, and caspase-14 expression, suggesting skin barrier repair. EC treatment also decreased keratin-16 expression and increased levels of Toll-like receptors 1 and 2 versus diluent, suggesting involvement in regulating the epidermal immune response. In 20 patients randomized 1:1 to EC or placebo, EC treatment at the elbow fold/popliteal fossa significantly decreased epidermal thickness after 2 months, and the number of blood vessels at the elbow fold after 1 and 2 months, versus placebo. EC significantly improved the skin hydration after 2 months versus baseline.

Conclusions: This novel multi-action EC may help to restore epidermal homeostasis and improve the skin of patients with AD. Results indicate that this novel multi-action EC could be a valid adjuvant therapy in patients with AD. Key Message: Novel multi-action emollient cream helps to restore epidermal homeostasis and improves the skin affected by AD.
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http://dx.doi.org/10.1159/000513055DOI Listing
February 2021

Comparative study of imiquimod 3.75% vs. photodynamic therapy for actinic keratosis of the scalp.

Photodermatol Photoimmunol Photomed 2021 Feb 10. Epub 2021 Feb 10.

Department of Medicine and Surgery, University of Parma, Parma, Italy.

Background/purpose: To assess efficacy, tolerability, adverse effects, recurrence, and aesthetic results of imiquimod 3.75% vs. photodynamic therapy with 5-aminolaevulinic acid (MAL-PDT) for actinic keratosis (AK).

Methods: A small randomized, intraindividual right-left pilot study for AK treatment of multiple scalp lesions was performed. Patients were treated with imiquimod and subsequently MAL-PDT (on opposite sides of the scalp) 14 days apart. Study end points were evaluated with clinical and dermoscopic examinations at 1, 3, 6, and 12 months.

Results: Nine male bald patients were enrolled. Imiquimod achieved a slightly higher overall clearance rate than MAP-PDT (68.1% vs 56.5%). According to AK degree of severity, clearance rates were greater for degree I and III with imiquimod (68.8%, 64.5% and 75% with imiquimod vs. 48%, 69.8%, and 66.7% for MAL-PDT, respectively). At 12 months, a slightly higher total recurrence rate was noted for imiquimod compared with MAL-PDT (9.9% vs. 8.6%); new lesions were 2 degree I for imiquimod and 4 degree I for MAL-PDT. For both treatments, pain was moderate/strong (even if MAL-PDT seems to be less tolerable) adverse effects are common and transient; aesthetic results excellent.

Conclusion: Both imiquimod and MAL-PDT were effective in the reduction in the number of AK. In the long-term, both present a good effectiveness maintained over time with excellent aesthetic results. A combination or sequential therapy could optimize the management of the cancerization field.
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http://dx.doi.org/10.1111/phpp.12671DOI Listing
February 2021

Efficacy of Dupilumab in Concomitant Atopic Dermatitis and Chronic Rhinosinusitis With Nasal Polyps: A Preliminary Study.

Allergy Asthma Immunol Res 2021 Mar;13(2):347-349

Dermatology Unit, Surgical, Medical and Dental Department of Morphological Sciences related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy.

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http://dx.doi.org/10.4168/aair.2021.13.2.347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840876PMC
March 2021

The Interplay between HGF/c-met Axis and Nox4 in BRAF Mutated Melanoma.

Int J Mol Sci 2021 Jan 13;22(2). Epub 2021 Jan 13.

Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.

Background: Melanoma is the leading cause of death due to cutaneous malignancy and its incidence is on the rise. Several signaling pathways, including receptor tyrosine kinases, have a role in the development and progression of melanocytic lesions and malignant melanoma. Among those, the hepatocyte growth factor (HGF)/c-met axis is emerging as a critical player because it can play a role in drug resistance. Indeed, 50% of melanoma patients present BRAF mutations, however, all responders develop resistance to the inhibitors typically within one year of treatment. Interestingly, BRAF inhibitors induce reactive oxygen species (ROS) in melanoma cells, therefore, the aim of this study was to investigate a possible interplay between HGF/c-met and ROS sources, such as NADPH oxidases (Nox).

Methods: The expression of c-met and Nox were quantified in 60 patients with primary cutaneous melanoma. In vitro experiments on melanoma primary cells and the cell line were performed to dissect the underpinned molecular mechanism.

Results: The outcome of interest was the correlation between the high positivity for both Nox4 and c-met and metastasis occurring at least 1 year later than melanoma diagnosis in BRAF mutated patients, in contrast to nonmutated. In vitro experiments demonstrated that the axis HGF/c-met/Nox4/ROS triggers the epithelial-mesenchymal transition.

Conclusions: The observed correlation suggests an interplay between c-met and Nox4 in promoting the onset of metastasis. This study suggests that Nox4 inhibitors could be associated to the current therapy used to treat melanoma patients with BRAF mutations.
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http://dx.doi.org/10.3390/ijms22020761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828605PMC
January 2021

A new deep learning approach integrated with clinical data for the dermoscopic differentiation of early melanomas from atypical nevi.

J Dermatol Sci 2021 Feb 2;101(2):115-122. Epub 2020 Dec 2.

Dermatology Unit, Department of Medical, Surgical and Neurosciences, University of Siena, Italy; Bioengineering Unit, Department of Medical Biotechnology, University of Siena, Italy.

Background: Timely recognition of malignant melanoma (MM) is challenging for dermatologists worldwide and represents the main determinant for mortality. Dermoscopic examination is influenced by dermatologists' experience and fails to achieve adequate accuracy and reproducibility in discriminating atypical nevi (AN) from early melanomas (EM).

Objective: We aimed to develop a Deep Convolutional Neural Network (DCNN) model able to support dermatologists in the classification and management of atypical melanocytic skin lesions (aMSL).

Methods: A training set (630 images), a validation set (135) and a testing set (214) were derived from the idScore dataset of 979 challenging aMSL cases in which the dermoscopic image is integrated with clinical data (age, sex, body site and diameter) and associated with histological data. A DCNN_aMSL architecture was designed and then trained on both dermoscopic images of aMSL and the clinical/anamnestic data, resulting in the integrated "iDCNN_aMSL" model. Responses of 111 dermatologists with different experience levels on both aMSL classification (intuitive diagnosis) and management decisions (no/long follow-up; short follow-up; excision/preventive excision) were compared with the DCNNs models.

Results: In the lesion classification study, the iDCNN_aMSL achieved the best accuracy, reaching an AUC = 90.3 %, SE = 86.5 % and SP = 73.6 %, compared to DCNN_aMSL (SE = 89.2 %, SP = 65.7 %) and intuitive diagnosis of dermatologists (SE = 77.0 %; SP = 61.4 %).

Conclusions: The iDCNN_aMSL proved to be the best support tool for management decisions reducing the ratio of inappropriate excision. The proposed iDCNN_aMSL model can represent a valid support for dermatologists in discriminating AN from EM with high accuracy and for medical decision making by reducing their rates of inappropriate excisions.
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http://dx.doi.org/10.1016/j.jdermsci.2020.11.009DOI Listing
February 2021

Anti-drug antibody detection with label-free electrolyte-gated organic field-effect transistors.

Chem Commun (Camb) 2021 Jan;57(3):367-370

Dipartimento di Scienze della Vita - Università di Modena e Reggio Emilia, Via Campi 103, 41125 Modena, Italy.

The efficacy of immunotherapy can be undermined by the development of an immune response against a drug/antibody mediated by anti-drug antibodies (ADAs) in treated patients. We present the first label-free EGOFET immunosensor that integrates a biological drug, Nivolumab (Opdivo©), as a specific recognition moiety to quantitatively and selectively detect ADAs against the drug. The limit of detection is 100 fM. This demonstration is a prelude to the detection of ADAs in a clinical setting in the treatment of different pathologies, and it also enables rapid screening of biological drugs for immunogenicity.
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http://dx.doi.org/10.1039/d0cc03399eDOI Listing
January 2021

Visible characteristics and structural modifications relating to enlarged facial pores.

Skin Res Technol 2020 Nov 20. Epub 2020 Nov 20.

Laboratoires Clarins, Pontoise, France.

Background: Many factors relate to enlargement and visibility of facial pores. However, how enlargement relates to modification of the skin structure is still poorly analysed. Therefore, our aim was to characterise the visible features and the micro-environment of facial pores.

Materials And Methods: We recruited 160 women, half of them with normal-size facial pores, the other half presenting enlarged pores. We analysed their right cheek using standardised photography, in vivo reflectance microscopy and optical coherence tomography.

Results: If the area of pores is indeed the most differentiating visible characteristic, enlarged facial pores are also denser and more contrasted. At the structural level, enlarged facial pores present a more regular organisation of keratinocytes, an irregular dermo-epidermal junction and a higher attenuation of collagen between the surface and deeper layers. Still, the most relevant alterations of enlarged facial pores are the presence of bright tubular structures surrounding hair follicles and enlarged hair shafts.

Conclusion: These observations suggest that alterations of the stroma could result in altered skin tensions, leading to the dilation of the infundibulum and enlarged hair shaft. The modified tension would also explain the more regular organisation of the keratinocytes and the irregular dermo-epidermal junction.
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http://dx.doi.org/10.1111/srt.12984DOI Listing
November 2020

Red dye-related tattoo reactions: Could optical coherence tomography be of help?

Skin Res Technol 2020 Nov 15. Epub 2020 Nov 15.

Dermatology Unit, Surgical, Medical and Dental Department of Morphological Sciences related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy.

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http://dx.doi.org/10.1111/srt.12966DOI Listing
November 2020

Folliculotropism in head and neck lentigo maligna and lentigo maligna melanoma.

J Dtsch Dermatol Ges 2021 02 9;19(2):223-229. Epub 2020 Nov 9.

Dermatology Department, University of Modena and Reggio Emilia, Modena, Italy.

Background: Lentigo maligna (LM) and lentigo maligna-melanoma (LMM) are histotypes of melanoma arising in skin with cumulative solar radiation damage. The extension of atypical melanocytes to the hair follicle (folliculotropism) is a histopathological feature of LM/LMM. Its role has not been totally clarified, but it may be correlated to treatment response in LM or to progression in LMM.

Objective: This retrospective, multicentric study aims to identify dermatoscopic features associated with folliculotropism in LMs/LMMs.

Patients And Methods: We analyzed cases of head and neck LMs/LMMs diagnosed between 2005-2014 at Melanoma Units, University of Bologna/Modena/Florence/Siena (Italy), Nice (France): 25 LMs and 73 LMMs were included.

Results: Grey circles (44 %) indicated an isthmic/bulb level of involvement, which were completely absent in the infundibular LM lesions (P = 0.041). In the group of LMMs, light/dark brown pseudonetwork and light brown structureless areas were an indicator of diffuse distribution of malignant melanocytes in the follicular units (P < 0.001 and P = 0.001, respectively), while grey circles indicated focal or diffuse distribution (P < 0.001).

Conclusions: A better understanding of the extension of malignant melanocytes is helpful, aiding clinicians in their decision to perform a radical excision or obtaining a biopsy in the most invasive area of the lesion, which includes potential folliculotropism.
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http://dx.doi.org/10.1111/ddg.14311DOI Listing
February 2021

Carbon Peel Laser Technique to Improve Skin Quality: Back to Science!

Dermatol Pract Concept 2020 Oct 26;10(4):e2020113. Epub 2020 Oct 26.

Dermatology Unit, Department of Surgical, Medical, Dental and Morphological Sciences related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy.

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http://dx.doi.org/10.5826/dpc.1004a113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588164PMC
October 2020

A Peculiar Case of Darier Disease in Blaschkoid Distribution.

Dermatol Pract Concept 2020 Oct 26;10(4):e2020078. Epub 2020 Oct 26.

Department of Surgical, Medical, Dental and Morphological Sciences, Transplant, Oncological and Regenerative Medicine; Dermatology Unit, University of Modena and Reggio Emilia, Modena, Italy.

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http://dx.doi.org/10.5826/dpc.1004a78DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588170PMC
October 2020

Segmentation of cellular patterns in confocal images of melanocytic lesions in vivo via a multiscale encoder-decoder network (MED-Net).

Med Image Anal 2021 01 7;67:101841. Epub 2020 Oct 7.

Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, 11377,NY, USA. Electronic address:

In-vivo optical microscopy is advancing into routine clinical practice for non-invasively guiding diagnosis and treatment of cancer and other diseases, and thus beginning to reduce the need for traditional biopsy. However, reading and analysis of the optical microscopic images are generally still qualitative, relying mainly on visual examination. Here we present an automated semantic segmentation method called "Multiscale Encoder-Decoder Network (MED-Net)" that provides pixel-wise labeling into classes of patterns in a quantitative manner. The novelty in our approach is the modeling of textural patterns at multiple scales (magnifications, resolutions). This mimics the traditional procedure for examining pathology images, which routinely starts with low magnification (low resolution, large field of view) followed by closer inspection of suspicious areas with higher magnification (higher resolution, smaller fields of view). We trained and tested our model on non-overlapping partitions of 117 reflectance confocal microscopy (RCM) mosaics of melanocytic lesions, an extensive dataset for this application, collected at four clinics in the US, and two in Italy. With patient-wise cross-validation, we achieved pixel-wise mean sensitivity and specificity of 74% and 92%, respectively, with 0.74 Dice coefficient over six classes. In the scenario, we partitioned the data clinic-wise and tested the generalizability of the model over multiple clinics. In this setting, we achieved pixel-wise mean sensitivity and specificity of 77% and 94%, respectively, with 0.77 Dice coefficient. We compared MED-Net against the state-of-the-art semantic segmentation models and achieved better quantitative segmentation performance. Our results also suggest that, due to its nested multiscale architecture, the MED-Net model annotated RCM mosaics more coherently, avoiding unrealistic-fragmented annotations.
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http://dx.doi.org/10.1016/j.media.2020.101841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885250PMC
January 2021

Analysis of Sentinel Node Biopsy and Clinicopathologic Features as Prognostic Factors in Patients With Atypical Melanocytic Tumors.

J Natl Compr Canc Netw 2020 10 1;18(10):1327-1336. Epub 2020 Oct 1.

Department of Pathology.

Background: Atypical melanocytic tumors (AMTs) include a wide spectrum of melanocytic neoplasms that represent a challenge for clinicians due to the lack of a definitive diagnosis and the related uncertainty about their management. This study analyzed clinicopathologic features and sentinel node status as potential prognostic factors in patients with AMTs.

Patients And Methods: Clinicopathologic and follow-up data of 238 children, adolescents, and adults with histologically proved AMTs consecutively treated at 12 European centers from 2000 through 2010 were retrieved from prospectively maintained databases. The binary association between all investigated covariates was studied by evaluating the Spearman correlation coefficients, and the association between progression-free survival and all investigated covariates was evaluated using univariable Cox models. The overall survival and progression-free survival curves were established using the Kaplan-Meier method.

Results: Median follow-up was 126 months (interquartile range, 104-157 months). All patients received an initial diagnostic biopsy followed by wide (1 cm) excision. Sentinel node biopsy was performed in 139 patients (58.4%), 37 (26.6%) of whom had sentinel node positivity. There were 4 local recurrences, 43 regional relapses, and 8 distant metastases as first events. Six patients (2.5%) died of disease progression. Five patients who were sentinel node-negative and 3 patients who were sentinel node-positive developed distant metastases. Ten-year overall and progression-free survival rates were 97% (95% CI, 94.9%-99.2%) and 82.2% (95% CI, 77.3%-87.3%), respectively. Age, mitotic rate/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss were factors affecting prognosis in the whole series and the sentinel node biopsy subgroup.

Conclusions: Age >20 years, mitotic rate >4/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss proved to be worse prognostic factors in patients with ATMs. Sentinel node status was not a clear prognostic predictor.
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http://dx.doi.org/10.6004/jnccn.2020.7582DOI Listing
October 2020

Automatic Quality Assessment of Reflectance Confocal Microscopy Mosaics using Attention-Based Deep Neural Network.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:1824-1827

Skin cancers are the most common cancers with an increased incidence, and a valid, early diagnosis may significantly reduce its morbidity and mortality. Reflectance confocal microscopy (RCM) is a relatively new, non-invasive imaging technique that allows screening lesions at a cellular resolution. However, one of the main disadvantages of the RCM is frequently occurring artifacts which makes the diagnostic process more time consuming and hard to automate using e.g. end-to-end deep learning approach. A tool to automatically determine the RCM mosaic quality could be beneficial for both the lesion classification and informing the user (dermatologist) about its quality in real-time, during the examination procedure. In this work, we propose an attention-based deep network to automatically determine if a given RCM mosaic has an acceptable quality. We achieved accuracy above 87% on the test set which may considerably improve further classification results and the RCM-based examination.
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http://dx.doi.org/10.1109/EMBC44109.2020.9176557DOI Listing
July 2020

Digital Biopsy with Fluorescence Confocal Microscope for Effective Real-time Diagnosis of Prostate Cancer: A Prospective, Comparative Study.

Eur Urol Oncol 2020 Sep 17. Epub 2020 Sep 17.

Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy.

Background: A microscopic analysis of tissue is the gold standard for cancer detection. Hematoxylin-eosin (HE) for the reporting of prostate biopsy (PB) is conventionally based on fixation, processing, acquisition of glass slides, and analysis with an analog microscope by a local pathologist. Digitalization and real-time remote access to images could enhance the reporting process, and form the basis of artificial intelligence and machine learning. Fluorescence confocal microscopy (FCM), a novel optical technology, enables immediate digital image acquisition in an almost HE-like resolution without requiring conventional processing.

Objective: The aim of this study is to assess the diagnostic ability of FCM for prostate cancer (PCa) identification and grading from PB.

Design, Setting, And Participants: This is a prospective, comparative study evaluating FCM and HE for prostate tissue interpretation. PBs were performed (March to June 2019) at a single coordinating unit on consecutive patients with clinical and laboratory indications for assessment. FCM digital images (n = 427) were acquired immediately from PBs (from 54 patients) and stored; corresponding glass slides (n = 427) undergoing the conventional HE processing were digitalized and stored as well. A panel of four international pathologists with diverse background participated in the study and was asked to evaluate all images. The pathologists had no FCM expertise and were blinded to clinical data, HE interpretation, and each other's evaluation. All images, FCM and corresponding HE, were assessed for the presence or absence of cancer tissue and cancer grading, when appropriate. Reporting was gathered via a dedicated web platform.

Outcome Measurements And Statistical Analysis: The primary endpoint is to evaluate the ability of FCM to identify cancer tissue in PB cores (per-slice analysis). FCM outcomes are interpreted by agreement level with HE (K value). Additionally, either FCM or HE outcomes are assessed with interobserver agreement for cancer detection (presence vs absence of cancer) and for the discrimination between International Society of Urologic Pathologists (ISUP) grade = 1 and ISUP grade > 1 (secondary endpoint).

Results And Limitations: Overall, 854 images were evaluated from each pathologist. PCa detection of FCM was almost perfectly aligned with HE final reports (95.1% of correct diagnosis with FCM, κ = 0.84). Inter-rater agreement between pathologists was almost perfect for both HE and FCM for PCa detection (0.98 for HE, κ = 0.95; 0.95 for FCM, κ = 0.86); for cancer grade attribution, only a moderate agreement was reached for both HE and FCM (HE, κ = 0.47; FCM, κ = 0.49).

Conclusions: FCM provides a microscopic, immediate, and seemingly reliable diagnosis for PCa. The real-time acquisition of digital images-without requiring conventional processing-offers opportunities for immediate sharing and reporting. FCM is a promising tool for improvements in cancer diagnostic pathways.

Patient Summary: Fluorescence confocal microscopy may provide an immediate, microscopic, and apparently reliable diagnosis of prostate cancer on prostate biopsy, overcoming the standard turnaround time of conventional processing and interpretation.
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http://dx.doi.org/10.1016/j.euo.2020.08.009DOI Listing
September 2020

Reflectance confocal microscopy for striae distansae treatment monitoring after CO fractional laser.

Dermatol Ther 2020 11 27;33(6):e14318. Epub 2020 Sep 27.

Department of Dermatology, University of Modena, Reggio Emilia, Italy.

The aim of this study is to describe the efficacy and safety of CO fractional laser to treat striae distensae (SD), before (T0) and 1 month after the last laser session (T1), in patients following different protocols based on the number of laser sessions, ≤4 and > 4. Efficacy was estimated with global assessment improvement scale (GAIS) performed by both physicians and patients, reflectance confocal microscopy (RCM), dermatology life quality index (DLQI). Safety was evaluated through pain assessment and adverse events. Eighteen patients with SD were enrolled. Clinical improvement of SD was observed in all patients at T1, as compared to T0. Furthermore, a reduction of RCM features of SD was observed at T1, above all in patients receiving >4 treatments, as compared to T0. Interestingly, we describe herein a new RCM feature of SD, the "neat-wall", corresponding to a distortion of the normal dermo-epidermal junction (DEJ), with a well-demarcated margin. A significant improvement of DLQI (P-value = .007) was also registered after SD treatment. Adverse events included temporary erythema and edema. In conclusion, the current study confirms the efficacy and safety of fractional CO laser, proposing RCM features, such as parallel collagen fibers and the neat-wall, as potential markers of SD treatment response.
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http://dx.doi.org/10.1111/dth.14318DOI Listing
November 2020

Hidradenitis Suppurativa: Surgical and Postsurgical Management.

Skin Appendage Disord 2020 Jul 14;6(4):195-201. Epub 2020 May 14.

Section of Dermatology. Department of Surgical, Medical, Dental and Morphological Sciences with Interest Transplant, Oncological and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy.

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory disorder. Several medical treatments, with varying degrees of efficacy, have been developed. However, in most cases of advanced HS, the definitive treatment option is often represented by surgical excisions.

Objective: Surgical techniques, reconstructive approach, and local wound care should be accurately designed in order to obtain the best result. In this review we analyze the possible surgical treatments and local wound care.

Methods: A MEDLINE search was performed on the various surgical treatments, reconstructive techniques, and local wound care.

Results: Surgical treatment is a common therapeutic modality for HS. Different surgical reconstructive techniques and post-surgical wound care approaches are described for the management of HS patients.

Conclusions: There were few high-quality evidence-based studies evaluating the surgical management of HS. Many disparate HS severity scores were used in these studies, making comparisons between them difficult. Nonetheless, research on different surgical approaches and wound care management has increased substantially in the past decade and it has given patients more surgical therapeutic strategies. The description of the best combinations and timing of surgery, wound care, and medical therapies will be a matter of future research for the definition of the optimal management of the HS patient.
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http://dx.doi.org/10.1159/000507297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445542PMC
July 2020