Impact of in vivo reflectance confocal microscopy on the number needed to treat melanoma in doubtful lesions

Background The number needed to treat ratio is an effective method for measuring accuracy in melanoma detection. Dermoscopy reduces the number of false positives and subsequently unnecessary excisions. In vivo confocal microscopy is a non-invasive technique which allows the examination of the skin with cellular resolution. Objectives To assess the impact of RCM analysis on the number of equivocal lesions, assumed to be melanocytic, excised for every melanoma. Methods Consecutive patients (n=343) presenting with doubtful lesions, were considered for enrolment. The lesions were analysed by dermoscopy and RCM and histopathological assessment was considered the reference standard. The main outcome was the number needed to treat, calculated as the proportion of equivocal lesions, excised for every melanoma. Results Dermoscopy alone obtained a hypothetical NNT of 3.73, the combination of dermoscopy and RCM identified 264 equivocal lesions that qualified for excision, 92 of which were confirmed to be a melanoma; resulting in a NNT of 2.87; whereas the analysis of RCM images classified as melanoma 103 lesions with a consequent NNT of 1.12; the difference in the reduction of this ratio was statistically significant (p< 0.0001) between the three groups. There was no significant improvement in sensitivity when comparing the combination of dermoscopy and RCM and RCM alone (94.56% vs. 97.82%; p = 0.043). However, the differences between specificities were statistically significant (p <0.000001), favouring RCM alone. Conclusion The addition of RCM analysis to dermoscopy reduces unnecessary excisions with a high diagnostic accuracy and could be a means for reducing the economic impact associated with the management of skin cancer

Association between confocal morphologic classification and clinical phenotypes of multiple primary and familial melanomas

Importance: The improved knowledge of clinical, morphologic, and epidemiologic heterogeneity of melanoma in the context of multiple primary and familial melanomas may improve prevention, diagnosis, and prognosis of melanoma. Objective: To characterize reflectance confocal microscopy (RCM) morphologic patterns of melanomas in multiple primary and familial melanomas. Design, Setting, and Participants: In this cross-sectional, retrospective study, patients in a hospital-based referral center were recruited from March 1, 2010, through August 31, 2013; data analysis was conducted from September 1, 2013, through May 31, 2014. Consecutive primary melanomas, documented by dermoscopic and confocal examination, from multiple primary and familial melanomas with known CDKN2A mutational status were studied. Main Outcomes and Measures: Epidemiologic, genetic, dermoscopic, and histologic data were evaluated according to an RCM morphologic classification: dendritic cell, round cell, dermal nest, combined, and nonclassifiable types. Results: Fifty-seven melanomas from 50 patients (28 women [56%] and 49 white patients [98%]) were included: 23 dendritic cell (40%), 21 round cell (37%), 2 dermal nests (4%), 2 combined (4%), and 9 nonclassifiable (16%). The median (SD) age of the participants was 53.0 (16.9) years (interquartile range, 41.8-71.2 years), and the median (SD) age at the first melanoma was 46.0 (17.1) years (interquartile range, 35.8-61.5 years). Dendritic cell melanoma was characterized by older age at diagnosis, phototypes 2 and 3, more intense solar exposure, and moderate to severe solar lentigines; it was the most prevalent confocal type in facial lesions and was associated with the lentigo maligna histologic subtype. Round cell melanomas were identified more often in the familial context and in individuals with phototype 1 skin types; RCM features, such as junctional thickening, dense dermal nests, and nucleated cells within papillary dermis, were more frequently found in this subtype. Dermal nest and combined melanoma were associated with the absence of pigmented network on dermoscopy and thicker tumors on histologic analysis. Nonclassifiable type was associated, by RCM, with the absence of pagetoid cells on confocal examination and lower frequency of marked atypia on melanocytes in the basal cell layer; it presented with lower ABCD Total Dermoscopy Scores and RCM scores compared with the other types. CDKN2A mutation carriers may develop any RCM type of melanoma. Conclusions and Relevance: Different routes to develop melanoma can be identified according to RCM morphologic classification, with dendritic cell melanomas being associated with chronic sun damage and round cell melanoma with early age at onset and phototype 1 in the context of multiple primary and familial melanomas. The morphologic expression of melanomas via dermoscopy and confocal examination varies according to differences in tumor stage and biological behavior

Temporal relationship of serum markers and tissue damage during acute intestinal ischemia/reperfusion

OBJECTIVE: It is essential to identify a serological marker of injury in order to study the pathophysiology of intestinal ischemia reperfusion. In this work, we studied the evolution of several serological markers after intestinal ischemia reperfusion injury in rats. The markers of non-specific cell damage were aspartate aminotransferase, alanine aminotransaminase, and lactic dehydrogenase, the markers of inflammation were tumor necrosis factor alpha, interleukin-6, and interleukin-1 beta, and the markers of intestinal mucosal damage were intestinal fatty acid binding protein and D-lactate. We used Chiús classification to grade the histopathological damage. METHODS: We studied 35 Wistar rats divided into groups according to reperfusion time. The superior mesenteric artery was clamped for 30 minutes, and blood and biopsies were collected at 1, 3, 6, 12, 24, and 48 hours after reperfusion. We plotted the mean ± standard deviation and compared the baseline and maximum values for each marker using Student's t-test. RESULTS: The maximum values of interleukin-1 beta and lactic dehydrogenase were present before the maximal histopathological damage. The maximum tumor necrosis factor alpha and D-lactate expressions coincided with histopathological damage. Alanine aminotransaminase and aspartate aminotransferase had a maximum expression level that increased following the histopathological damage. The maximum expressions of interluken-6 and intestinal fatty acid binding protein were not significantly different from the Sham treated group. CONCLUSION: For the evaluation of injury secondary to acute intestinal ischemia reperfusion with a 30 minute ischemia period, we recommend performing histopathological grading, quantification of D-lactate, which is synthesized by intestinal bacteria and is considered an indicator of mucosal injury, and quantification of tumor necrosis factor alpha as indicators of acute inflammation three hours after reperfusion

Immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in patients receiving secukinumab: a literature review

Purpose: There is a paucity of evidence on the impact of immune-mediated inflammatory disease (IMID) treatments on the immunogenicity of SARS-CoV-2 vaccination. The purpose of this literature review is to address the question of whether patients with IMIDs receiving secukinumab, a fully human anti-interleukin-17A monoclonal antibody, have an adequate immune response after SARS-CoV-2 vaccination. Materials and Methods: Clinical studies that evaluated the effect of secukinumab on immune responses in patients with IMIDs after SARS-CoV-2 vaccination were searched in publication databases, including Medline and Embase, until May 2022. Results: From the 53 articles identified, a total of 11 articles were included. Overall, the majority of the patients treated with secukinumab elicited an adequate immune response to SARS-CoV-2 vaccines. Patients receiving secukinumab for IMIDs developed cellular immune responses following vaccination with the BNT162b2 vaccine, and there were no significant differences in the overall humoral and cellular immune responses between patients and healthy individuals. The third dose of the BNT162b2 mRNA vaccine resulted in a positive antibody response in secukinumab-treated patients. Conclusion: The available data provide no evidence of impairment in immunological response to SARS-CoV-2 vaccines by secukinumab in patients with IMIDs

Impact of in vivo reflectance confocal microscopy on the number needed to treat melanoma in doubtful lesions

Background The number needed to treat ratio is an effective method for measuring accuracy in melanoma detection. Dermoscopy reduces the number of false positives and subsequently unnecessary excisions. In vivo confocal microscopy is a non-invasive technique which allows the examination of the skin with cellular resolution. Objectives To assess the impact of RCM analysis on the number of equivocal lesions, assumed to be melanocytic, excised for every melanoma. Methods Consecutive patients (n=343) presenting with doubtful lesions, were considered for enrolment. The lesions were analysed by dermoscopy and RCM and histopathological assessment was considered the reference standard. The main outcome was the number needed to treat, calculated as the proportion of equivocal lesions, excised for every melanoma. Results Dermoscopy alone obtained a hypothetical NNT of 3.73, the combination of dermoscopy and RCM identified 264 equivocal lesions that qualified for excision, 92 of which were confirmed to be a melanoma; resulting in a NNT of 2.87; whereas the analysis of RCM images classified as melanoma 103 lesions with a consequent NNT of 1.12; the difference in the reduction of this ratio was statistically significant (p< 0.0001) between the three groups. There was no significant improvement in sensitivity when comparing the combination of dermoscopy and RCM and RCM alone (94.56% vs. 97.82%; p = 0.043). However, the differences between specificities were statistically significant (p <0.000001), favouring RCM alone. Conclusion The addition of RCM analysis to dermoscopy reduces unnecessary excisions with a high diagnostic accuracy and could be a means for reducing the economic impact associated with the management of skin cancer

Impact of in vivo reflectance confocal microscopy on the number needed to treat melanoma in doubtful lesions

Background The number needed to treat ratio is an effective method for measuring accuracy in melanoma detection. Dermoscopy reduces the number of false positives and subsequently unnecessary excisions. In vivo confocal microscopy is a non-invasive technique which allows the examination of the skin with cellular resolution. Objectives To assess the impact of RCM analysis on the number of equivocal lesions, assumed to be melanocytic, excised for every melanoma. Methods Consecutive patients (n=343) presenting with doubtful lesions, were considered for enrolment. The lesions were analysed by dermoscopy and RCM and histopathological assessment was considered the reference standard. The main outcome was the number needed to treat, calculated as the proportion of equivocal lesions, excised for every melanoma. Results Dermoscopy alone obtained a hypothetical NNT of 3.73, the combination of dermoscopy and RCM identified 264 equivocal lesions that qualified for excision, 92 of which were confirmed to be a melanoma; resulting in a NNT of 2.87; whereas the analysis of RCM images classified as melanoma 103 lesions with a consequent NNT of 1.12; the difference in the reduction of this ratio was statistically significant (p< 0.0001) between the three groups. There was no significant improvement in sensitivity when comparing the combination of dermoscopy and RCM and RCM alone (94.56% vs. 97.82%; p = 0.043). However, the differences between specificities were statistically significant (p <0.000001), favouring RCM alone. Conclusion The addition of RCM analysis to dermoscopy reduces unnecessary excisions with a high diagnostic accuracy and could be a means for reducing the economic impact associated with the management of skin cancer

High-definition optical coherence tomography algorithm for discrimination of basal cell carcinoma from clinical BCC imitators and differentiation between common subtypes

Background Preliminary studies have described morphological features of basal cell carcinoma (BCC) imaged by high-definition optical coherence tomography (HD-OCT) and suggested that this technique may aid in its diagnosis and management. However, systematic studies evaluating the accuracy of HD-OCT for the diagnosis of BCC are lacking. Objective The aim of this study was to identify three-dimensional (3-D) HD-OCT features able i) to distinguish BCC from clinical BCC imitators and ii) to discriminate between the most common BCC subtypes. Based on these particular features, a diagnostic algorithm will be suggested. Method A total of 50 histopathologically confirmed BCCs (18 superficial, 19 nodular, 13 infiltrative) were imaged by HD-OCT at the centre of the lesion prior to standard surgical excision and subsequent histopathological analysis. Fifty images of clinical BCC imitators were also retrieved as a «pitfalls» group. Results The simultaneous presence of grey/dark subepidermal (hemi-spherical) or intradermal lobulated structure(s) presenting a typical cockade feature in both HD-OCT modes was a significant feature for BCC diagnosis. Features discriminating between BCC subtypes were location of the roof of BCC lobules, vascular pattern of the papillary plexus and stretching effect on the stroma. Clinical BCC imitators such as actinic keratosis, compound and intradermal naevi, amelanotic melanoma, sebaceous hyperplasia and small haemangioma could be differentiated from BCC by means of HD-OCT. Conclusion This study provides a thorough description of 3-D HD-OCT features that can permit discrimination of BCC from clinical BCC imitators and differentiation of BCC subtypes. Based on these features, a diagnostic algorithm is proposed which requires additional validation, but enhances current understanding of the morphological correlates of HD-OCT images in skin.SCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe

Association between confocal morphologic classification and clinical phenotypes of multiple primary and familial melanomas

Importance: The improved knowledge of clinical, morphologic, and epidemiologic heterogeneity of melanoma in the context of multiple primary and familial melanomas may improve prevention, diagnosis, and prognosis of melanoma. Objective: To characterize reflectance confocal microscopy (RCM) morphologic patterns of melanomas in multiple primary and familial melanomas. Design, Setting, and Participants: In this cross-sectional, retrospective study, patients in a hospital-based referral center were recruited from March 1, 2010, through August 31, 2013; data analysis was conducted from September 1, 2013, through May 31, 2014. Consecutive primary melanomas, documented by dermoscopic and confocal examination, from multiple primary and familial melanomas with known CDKN2A mutational status were studied. Main Outcomes and Measures: Epidemiologic, genetic, dermoscopic, and histologic data were evaluated according to an RCM morphologic classification: dendritic cell, round cell, dermal nest, combined, and nonclassifiable types. Results: Fifty-seven melanomas from 50 patients (28 women [56%] and 49 white patients [98%]) were included: 23 dendritic cell (40%), 21 round cell (37%), 2 dermal nests (4%), 2 combined (4%), and 9 nonclassifiable (16%). The median (SD) age of the participants was 53.0 (16.9) years (interquartile range, 41.8-71.2 years), and the median (SD) age at the first melanoma was 46.0 (17.1) years (interquartile range, 35.8-61.5 years). Dendritic cell melanoma was characterized by older age at diagnosis, phototypes 2 and 3, more intense solar exposure, and moderate to severe solar lentigines; it was the most prevalent confocal type in facial lesions and was associated with the lentigo maligna histologic subtype. Round cell melanomas were identified more often in the familial context and in individuals with phototype 1 skin types; RCM features, such as junctional thickening, dense dermal nests, and nucleated cells within papillary dermis, were more frequently found in this subtype. Dermal nest and combined melanoma were associated with the absence of pigmented network on dermoscopy and thicker tumors on histologic analysis. Nonclassifiable type was associated, by RCM, with the absence of pagetoid cells on confocal examination and lower frequency of marked atypia on melanocytes in the basal cell layer; it presented with lower ABCD Total Dermoscopy Scores and RCM scores compared with the other types. CDKN2A mutation carriers may develop any RCM type of melanoma. Conclusions and Relevance: Different routes to develop melanoma can be identified according to RCM morphologic classification, with dendritic cell melanomas being associated with chronic sun damage and round cell melanoma with early age at onset and phototype 1 in the context of multiple primary and familial melanomas. The morphologic expression of melanomas via dermoscopy and confocal examination varies according to differences in tumor stage and biological behavior

Association between confocal morphologic classification and clinical phenotypes of multiple primary and familial melanomas

Importance: The improved knowledge of clinical, morphologic, and epidemiologic heterogeneity of melanoma in the context of multiple primary and familial melanomas may improve prevention, diagnosis, and prognosis of melanoma. Objective: To characterize reflectance confocal microscopy (RCM) morphologic patterns of melanomas in multiple primary and familial melanomas. Design, Setting, and Participants: In this cross-sectional, retrospective study, patients in a hospital-based referral center were recruited from March 1, 2010, through August 31, 2013; data analysis was conducted from September 1, 2013, through May 31, 2014. Consecutive primary melanomas, documented by dermoscopic and confocal examination, from multiple primary and familial melanomas with known CDKN2A mutational status were studied. Main Outcomes and Measures: Epidemiologic, genetic, dermoscopic, and histologic data were evaluated according to an RCM morphologic classification: dendritic cell, round cell, dermal nest, combined, and nonclassifiable types. Results: Fifty-seven melanomas from 50 patients (28 women [56%] and 49 white patients [98%]) were included: 23 dendritic cell (40%), 21 round cell (37%), 2 dermal nests (4%), 2 combined (4%), and 9 nonclassifiable (16%). The median (SD) age of the participants was 53.0 (16.9) years (interquartile range, 41.8-71.2 years), and the median (SD) age at the first melanoma was 46.0 (17.1) years (interquartile range, 35.8-61.5 years). Dendritic cell melanoma was characterized by older age at diagnosis, phototypes 2 and 3, more intense solar exposure, and moderate to severe solar lentigines; it was the most prevalent confocal type in facial lesions and was associated with the lentigo maligna histologic subtype. Round cell melanomas were identified more often in the familial context and in individuals with phototype 1 skin types; RCM features, such as junctional thickening, dense dermal nests, and nucleated cells within papillary dermis, were more frequently found in this subtype. Dermal nest and combined melanoma were associated with the absence of pigmented network on dermoscopy and thicker tumors on histologic analysis. Nonclassifiable type was associated, by RCM, with the absence of pagetoid cells on confocal examination and lower frequency of marked atypia on melanocytes in the basal cell layer; it presented with lower ABCD Total Dermoscopy Scores and RCM scores compared with the other types. CDKN2A mutation carriers may develop any RCM type of melanoma. Conclusions and Relevance: Different routes to develop melanoma can be identified according to RCM morphologic classification, with dendritic cell melanomas being associated with chronic sun damage and round cell melanoma with early age at onset and phototype 1 in the context of multiple primary and familial melanomas. The morphologic expression of melanomas via dermoscopy and confocal examination varies according to differences in tumor stage and biological behavior