Preoperative 15-MHz Ultrasound Assessment of Tumor Thickness in Malignant Melanoma

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Abbreviations: CLE indicates cutaneous lupus erythematosus; SLE, systemic lupus erythematosus; ANA, antinuclear antibodies; aPTT, activated partial thromboplastin time; LA, lupus anticoagulant; ACA, anticardiolipin antibodies; anti-β2GPI, anti-β2-glycoprotein I; APS, antiphospholipid syndrome." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "P. García-Martín, C. García-García, J. Fraga, A. García-Díez" "autores" => array:4 [ 0 => array:2 [ "nombre" => "P." "apellidos" => "García-Martín" ] 1 => array:2 [ "nombre" => "C." "apellidos" => "García-García" ] 2 => array:2 [ "nombre" => "J." "apellidos" => "Fraga" ] 3 => array:2 [ "nombre" => "A." 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Fernández Canedo, M. de Troya Martín, R. Fúnez Liébana, F. Rivas Ruiz, G. Blanco Eguren, N. Blázquez Sánchez" "autores" => array:6 [ 0 => array:4 [ "nombre" => "I." "apellidos" => "Fernández Canedo" "email" => array:1 [ 0 => "inesbier@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "¿" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "M." "apellidos" => "de Troya Martín" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "R." "apellidos" => "Fúnez Liébana" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "F." "apellidos" => "Rivas Ruiz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 4 => array:3 [ "nombre" => "G." 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"apellidos" => "Blázquez Sánchez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital Costa del Sol, Marbella, Málaga, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Costa del Sol, Marbella, Málaga, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Unidad de Investigación, Hospital Costa del Sol, Marbella, Málaga, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Radiología, Hospital Costa del Sol, Marbella, Málaga, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Evaluación de la ecografía cutánea de 15 Mhz en la estimación preoperatoria del espesor tumoral en el melanoma maligno" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 742 "Ancho" => 2167 "Tamanyo" => 180325 ] ] "descripcion" => array:1 [ "en" => "Ultrasound and histologic assessment of tumor thickness." ] ] ] "textoCompleto" => "IntroductionTumor thickness is of great importance in the management of cutaneous malignant melanoma because it is used to determine the prognosis and is a key factor in planning surgical margins and selecting candidates for sentinel node biopsy.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>Breslow depth is the standard measure of tumor thickness in primary cutaneous melanoma.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> A histologic measurement, Breslow depth requires a preoperative excisional skin biopsy and, in addition to being invasive, the procedure may delay definitive surgical treatment because it involves a 2-stage intervention.Cutaneous ultrasound is a noninvasive imaging technique for visualizing the interior layers of the skin. The use of this tool in the field of dermatology has been studied in recent years.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> Although the majority of early studies used 20-MHz probes capable of measuring lesions at a depth of 6 to 8mm, many others used lower-resolution probes (10-15MHz) because these were available in most hospitals. However, the current trend is to use higher-resolution probes (75-100MHz), which measure lesions confined to the epidermis and dermis more accurately. In cutaneous malignant melanoma, cutaneous ultrasound offers the possibility of estimating tumor thickness in vivo, thus avoiding excisional biopsy and speeding up surgical treatment planning.<a class="elsevierStyleCrossRefs" href="#bib0015">3–5</a> Results of recent studies of the validity and utility of cutaneous ultrasound in the management of cutaneous malignant melanoma have been inconsistent.<a class="elsevierStyleCrossRefs" href="#bib0030">6–12</a>The aim of this study was to evaluate cutaneous ultrasound as a tool for measuring tumor thickness in cutaneous malignant melanoma. The histologic variables that affect ultrasound assessment of tumor thickness are also analyzed.Material and MethodsThis retrospective study evaluated the records of a consecutive series of patients with cutaneous malignant melanomas who underwent surgery between 2008 and 2010 in the dermatology department of the Hospital Costa del Sol. In all cases, members of the hospital's radiology department had performed a preoperative assessment of the lesion using a Toshiba Aplio XG 15-Mhz ultrasound probe to determine tumor thickness. Tumor thickness had been calculated automatically as the maximum vertical distance from the entry echo to the lowest hypoechoic signal, expressed in mm (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The histologic measure of thickness (Breslow depth) had been determined by a pathologist experienced in dermatopathology using an ocular micrometer to measure the maximum distance between the highest level of the stratum granulosum of the epidermis and the deepest point of the tumor, expressed in mm (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The histologic presence of ulceration, regression (absent, < 50%, > 50%), inflammatory infiltrate (absent, mild, moderate, severe), and associated nevi had also been recorded.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>The study was approved by the ethics committee of Hospital Costa del Sol.Statistical AnalysisWe compared the ultrasound measurement of tumor thickness against the results obtained with the gold standard method (Breslow depth), using the Pearson correlation coefficient and the intraclass correlation coefficient to quantify the degree of correlation and agreement between the 2 variables. To study the association between histologic variables (ulceration, regression, inflammatory infiltrate, and presence of nevi) and ultrasound assessment of thickness, bivariate analysis was performed, taking as the dependent variable the overestimation of thickness by ultrasound (+ 0.1mm) compared with Breslow depth, using χ2 tests and, where appropriate, the Fisher exact test. Statistical significance was set at P<.05. Finally, we studied the sensitivity, specificity, and positive and negative predictive values of cutaneous ultrasound against those of the gold standard for the correct classification of thick melanomas (Breslow depth > 1mm) with a 95% CI.ResultsWe studied 79 melanomas from 79 patients (53% of them women) with a mean (SD) age of 56.8 (16.2) years; 42% were located on the trunk, 40% on the limbs, and 18% on the head and neck. Melanomas in situ accounted for 45% of the tumors (n=35) and the remaining 55% were invasive tumors (n=44; 27 melanomas ≤ 1mm, 17 melanomas > 1mm). The mean Breslow depth of the series was 0.8 (1.4) mm. The mean thickness as measured by ultrasound was 1.2 (1.7) mm. The histologic findings are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>The Pearson correlation coefficient between ultrasound assessment of thickness and Breslow depth was 0.678 (P<.001) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The value of the intraclass correlation coefficient measuring agreement between the ultrasound assessment of thickness and Breslow depth was 0.78 (95% CI, 0.61-0.88).<elsevierMultimedia ident="fig0010"></elsevierMultimedia>Bivariate analysis showed that ultrasound tended to overestimate tumor thickness in the presence of moderate to severe inflammatory infiltrate and nevi, though this tendency was not statistically significant (P>.05) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Classic sensitivity tests showed that the sensitivity of ultrasound for the diagnosis of thick melanomas (Breslow depth > 1mm) was 82%, specificity was 80%, and positive and negative predictive values were 54% and 94%, respectively (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>DiscussionIn this study we analyzed the accuracy of cutaneous ultrasound as a tool for measuring tumor thickness in a consecutive series of 79 primary melanomas. Of interest is the high proportion of minimally invasive melanomas in situ, a finding that we attribute to the systematic use of dermoscopy in the diagnosis of pigmented skin lesions and to the continuous application of primary prevention strategies in our population.We found moderate correlation and agreement between ultrasound and histologic measures, whereas most earlier studies<a class="elsevierStyleCrossRefs" href="#bib0030">6–10</a> have reported good correlation. Tacke et al.,<a class="elsevierStyleCrossRef" href="#bib0030">6</a> using a 20-MHz probe on a series of 259 melanomas, reported a correlation coefficient of 0.88 (lesions of 0.55 to 0.95mm were classified incorrectly by ultrasound in 34% of cases and lesions of 1.30 to 1.70mm were classified incorrectly in 50% of cases). Conversely, Serrone et al.,<a class="elsevierStyleCrossRef" href="#bib0035">7</a> using a 20-MHz probe on a series of 261 lesions, reported a correlation coefficient of 0.95 in melanomas larger than 1.51mm, finding the lowest correlation in lesions smaller than 0.75mm. The results reported by Kaikaris et al.,<a class="elsevierStyleCrossRef" href="#bib0040">8</a> using a 14-MHz probe, were similar (r=0.283 in melanomas of 1–2mm and r=0.869 in melanomas larger than 2mm). Many factors make comparison between studies difficult, including the use of diverse probes, differences between the series studied, the inclusion of benign lesions (mainly nevi),<a class="elsevierStyleCrossRef" href="#bib0035">7</a> and the exclusion of in situ lesions<a class="elsevierStyleCrossRef" href="#bib0045">9</a> in the belief that ultrasound does not visualize epidermal lesions.Some histologic features of tumors may alter the ultrasound assessment of thickness.<a class="elsevierStyleCrossRef" href="#bib0050">10</a> Hoffman et al.<a class="elsevierStyleCrossRef" href="#bib0055">11</a> found that the cause of 80% of cases of overestimation was the presence of inflammatory infiltrate. In our series, cutaneous ultrasound tended to overestimate tumor thickness in comparison with the histologic measure in the presence of moderate to severe inflammatory infiltrate and associated nevi, though no statistical significance was found (P>.05). These histologic features act as artifacts and interfere with the ultrasound assessment of the tumor because cutaneous ultrasound does not differentiate between tumor cells and inflammatory or nevus cells.The sensitivity, specificity, and positive and negative predictive values for the diagnosis of thick melanomas (>1mm) were 82%, 80%, 54%, and 94%, respectively. These results suggest that cutaneous ultrasound would properly stage the tumor and allow a single surgical intervention to be planned in approximately 80% of melanomas. However, it would not provide an accurate measurement on which to base a therapeutic decision in 20% of melanomas. Cutaneous ultrasound showed high discriminatory capacity for thin melanomas but was less successful at discriminating thick melanomas. Some authors have developed diagnostic algorithms that increase the diagnostic accuracy for thick melanomas by combining clinical, dermoscopic, and ultrasound findings, reaching a sensitivity of 97% and a specificity of 100%.<a class="elsevierStyleCrossRef" href="#bib0060">12</a>Almost half the melanomas assessed by ultrasound as thick were in fact thin (< 1mm). This finding is explained by the frequent association of inflammatory infiltrate and nevi with the melanomas in our series. This tendency towards overestimation can be remedied by using higher-frequency probes, which have a higher resolution.<a class="elsevierStyleCrossRef" href="#bib0065">13</a>The results of one study, in line with our findings, showed a particularly good correspondence between ultrasound and histologic measurements using a 30-MHz probe when the lesions were smaller than 1mm in a series of 68 melanomas and an even better correspondence in lesions on the sole (r=0.945).<a class="elsevierStyleCrossRef" href="#bib0070">14</a> In contrast, Machet et al.,<a class="elsevierStyleCrossRef" href="#bib0075">15</a> using a 20-MHz probe, found lesions on the sole to be difficult to measure because of the thickness of the stratum corneum.In the ultrasound estimation of tumor thickness our results contrast with those published in a recent prospective study of 54 cutaneous malignant melanomas, which reported sensitivity, specificity, and positive and negative predictive values in the diagnosis of thick melanomas (> 1mm) of 86%, 97%, 95%, and 91%, respectively.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> The diagnostic accuracy of cutaneous ultrasound in that study was striking despite the lower ultrasound resolution of the probe used by the authors (10 Mhz). These results could be explained by the high proportion of melanomas later found to be thick on histology, which would be more accurately measured by ultrasound assessment because the presence of other histologic factors would not alter their ultrasound assessment as thick melanomas.The present study had several limitations. The small size of our series made it difficult to interpret the results with regard to the influence of histologic findings on the ultrasound assessment of thickness, so it was not possible to establish causal relationships between histologic and ultrasound findings. Interpersonal variability may interfere in the ultrasound assessment of tumor thickness, though the use of standardized procedure minimizes this bias.Technological advances in ultrasound, such as the use of contrast agents,<a class="elsevierStyleCrossRef" href="#bib0025">5</a> and the incorporation of new in vivo microscopy techniques, including dermoscopy<a class="elsevierStyleCrossRefs" href="#bib0085">17,18</a> and confocal microscopy,<a class="elsevierStyleCrossRef" href="#bib0095">19</a> are encouraging and their combined use will improve the preoperative diagnosis of melanoma in the near future.In conclusion, cutaneous ultrasound is a tool of great interest in the preoperative study of cutaneous malignant melanoma. It identifies thin melanomas fairly accurately and can be useful for planning appropriate surgical margins. Further studies are necessary to confirm whether certain histologic characteristics of the tumor, such as the presence of moderate to severe inflammatory infiltrate and associated nevi, can lead to an overestimation of thickness by ultrasound, limiting the clinical utility of this imaging technique in the management of cutaneous malignant melanoma.Ethical ConsiderationsProtection of persons and animalsThe authors state that no experiments on humans or animals were performed in this study.Data confidentialityThe authors state that no patient data appear in this article.Right to privacy and informed consentThe authors state that no patient data appear in this article.Conflicts of interestThe authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:2 [ "identificador" => "xres97873" "titulo" => array:6 [ 0 => "Abstract" 1 => "Background" 2 => "Objectives" 3 => "Materials and methods" 4 => "Results" 5 => "Conclusions" ] ] 1 => array:2 [ "identificador" => "xpalclavsec85029" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres97872" "titulo" => array:6 [ 0 => "Resumen" 1 => "Introducción" 2 => "Objetivos" 3 => "Material y métodos" 4 => "Resultados" 5 => "Conclusión" ] ] 3 => array:2 [ "identificador" => "xpalclavsec85028" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and Methods" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Statistical Analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0020" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0025" "titulo" => "Discussion" ] 8 => array:3 [ "identificador" => "sec0030" "titulo" => "Ethical Considerations" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Protection of persons and animals" ] 1 => array:2 [ "identificador" => "sec0040" "titulo" => "Data confidentiality" ] 2 => array:2 [ "identificador" => "sec0045" "titulo" => "Right to privacy and informed consent" ] 3 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflicts of interest" ] ] ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2012-01-16" "fechaAceptado" => "2012-06-27" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec85029" "palabras" => array:3 [ 0 => "Cutaneous ultrasound" 1 => "Tumour thickness" 2 => "Melanoma" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec85028" "palabras" => array:3 [ 0 => "Ecografía cutánea" 1 => "Espesor tumoral" 2 => "Melanoma" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "BackgroundTumor thickness is of great importance in the management of cutaneous malignant melanoma (MM): this variable not only affects prognosis but is also a key factor in planning surgical margins and selecting candidates for sentinel node biopsy. Breslow depth is the standard histologic measure of thickness, but technological advances have provided imaging techniques such as cutaneous ultrasound that can potentially assess tumor thickness and enable prompt initiation of definitive treatment. Objectivesa) To evaluate the utility of ultrasound assessment of tumor thickness in MM, and b) to analyze histologic variables that affect ultrasound assessments of thickness. Materials and methodsRetrospective study of a consecutive series of 79 primary cutaneous MMs in which tumor thickness had been assessed by 15-MHz ultrasound before surgery. We gathered data from histology reports, studying Breslow depth and the presence of ulceration, regression, inflammatory infiltrate, and associated nevi. Correlation coefficients were calculated to evaluate the strength of association between Breslow depth and thickness assessed by ultrasound. We also calculated the sensitivity, specificity, and positive and negative predictive values of ultrasound measurement in the diagnosis of MMs more than 1mm thick. Associations between histologic variables and the overestimation of thickness by ultrasound were also analyzed. ResultsThe 79 primary MMs studied had a mean (SD) Breslow depth of 0.8 (1.4) mm. There was moderate correlation and agreement between Breslow depth and the ultrasound assessment of thickness (Pearson correlation coefficient, 0.678; intraclass correlation coefficient, 0.78). The tendency of ultrasound to overestimate thickness was nonsignificantly related to the presence of a moderate to intense infiltrate and associated nevi (P>.05). The sensitivity of ultrasound for the diagnosis of MM over 1mm thick was 82%; specificity was 80%, and positive and negative predictive values were 54% and 94%, respectively. ConclusionsUltrasound imaging quite correctly identifies thin MMs and can be useful for planning adequate surgical margins; however, there are limitations on its usefulness in the diagnosis of thick MMs. Additional studies are required to confirm whether certain histologic characteristics, such as the presence of a moderate to intense inflammatory infiltrate or associated nevi can lead to overestimation of thickness by ultrasound, limiting the clinical utility of this imaging technique in MM management." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "IntroducciónEl espesor tumoral es una variable de gran trascendencia en el manejo clínico del melanoma maligno cutáneo (MMC), ya que no solo establece el pronóstico, sino que además determina la planificación de márgenes quirúrgicos y selecciona a aquellos pacientes candidatos a biopsia selectiva de ganglio centinela. El índice de Breslow (IB) es el procedimiento histométrico estándar para la determinación del espesor tumoral del melanoma. El desarrollo de técnicas de imagen, como la ecografía cutánea (EC), plantea la posibilidad de realizar una estimación no invasiva que agiliza la instauración del tratamiento definitivo. Objetivosa) Evaluar la EC como instrumento de medición del espesor tumoral en el MMC, y b) analizar los factores histológicos que influyen en la estimación del espesor ecográfico. Material y métodosEstudio retrospectivo de una serie consecutiva de 79 melanomas cutáneos primarios. En todos los casos, se practicó un estudio ecográfico preoperatorio con una sonda de 15 Mhz para la determinación del espesor tumoral (EE). Se analizaron los exámenes histológicos, estudiándose el IB, además de la presencia de ulceración, regresión, infiltrado inflamatorio y nevus. Se estudian el grado de correlación y el nivel de concordancia entre los valores de EE e IB. Se estiman la sensibilidad, la especificidad y los valores predictivos de la EC en el diagnóstico de melanomas de espesor >1mm. Se analiza la relación de las variables histológicas en la determinación del EE. ResultadosSe estudian 79 melanomas primarios, IB medio: 0.8mm (DE: 1,4). La EC evidenció un grado de correlación y un nivel de concordancia moderado con respecto al IB (coeficiente de correlación de Pearson: 0.678, coeficiente de correlación intraclase: 0.78, respectivamente). La EC mostró tendencia a sobrestimar el espesor histológico en relación con la presencia de infiltrado inflamatorio moderado-intenso y nevus, sin alcanzar significación estadística (p>0.05). La EC mostró valores de sensibilidad y especificidad, y valores predictivos positivo y negativo para el diagnóstico de melanomas gruesos (>1mm) del 82, el 80, el 54 y el 94%, respectivamente. ConclusiónLa EC permite discriminar con bastante precisión melanomas finos y planificar márgenes quirúrgicos adecuados, pero presenta limitaciones para el diagnóstico de melanomas gruesos. Son necesarios más estudios para confirmar si determinadas características histológicas del tumor, como la presencia de infiltrado inflamatorio moderado-intenso y nevus, pueden condicionar una sobrestimación del espesor ecográfico, limitando su aplicabilidad clínica en el manejo del MMC." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Fernández Canedo I, et al. Evaluación de la ecografía cutánea de 15 Mhz en la estimación preoperatoria del espesor tumoral en el melanoma maligno. Actas Dermosifiliogr. 2013;104:227–31." ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 742 "Ancho" => 2167 "Tamanyo" => 180325 ] ] "descripcion" => array:1 [ "en" => "Ultrasound and histologic assessment of tumor thickness." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1340 "Ancho" => 1632 "Tamanyo" => 114314 ] ] "descripcion" => array:1 [ "en" => "Scatter plot of histologic and ultrasound assessment of tumor thickness." ] ] 2 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Histology(n=79) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">In Situ (n=36) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">≤1mm (n=27) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">>1mm (n=16) \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ulceration: yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Regression:>50% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Inflammatory infiltrate: moderate-intense \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Associated nevus: yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab183312.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Histologic Characteristics of the Melanomas." ] ] 3 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">No Overestimation</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Overestimation (+ 0.1 mm)</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">P \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">n \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">n \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Regression</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Absent \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">80.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.43 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 50% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">41.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">> 50% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">44.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">55.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ulceration</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">66.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.23 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">44 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Inflammatory infiltrate</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Absent-mild \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">65.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.26 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Moderate-severe \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Associated nevus</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">43.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.15 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">64.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">35.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab183311.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Relationship of Ultrasound Assessment of Thickness and Histological Variables." ] ] 4 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Histology</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">≤1mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">>1mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ultrasound \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≤1mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>1mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">79 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab183313.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Histologic and Ultrasound Assessment of Thickness of the Series of 79 Melanomas." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:19 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Revised U. K. Guidelines for the Management of Cutaneous Melanoma 2010" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.R. Marsden" 1 => "J.A. Newton-Bishop" 2 => "L. Burrows" 3 => "M. Cook" 4 => "P.G. Corrie" 5 => "N.H. Cox" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2133.2010.09883.x" "Revista" => array:6 [ "tituloSerie" => "Br J Dermatol" "fecha" => "2010" "volumen" => "163" "paginaInicial" => "238" "paginaFinal" => "256" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20608932" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Thickness, cross sectional areas and depth of invasion in the prognosis of malignant melanoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "A. Breslow" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ann Surg" "fecha" => "1970" "volumen" => "172" "paginaInicial" => "902" "paginaFinal" => "908" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/5477666" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ultrasound scanning in dermatology" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.H. Schmid-Wendtner" 1 => "W. Burgdorf" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Arch Dermatology" "fecha" => "2005" "volumen" => "141" "paginaInicial" => "217" "paginaFinal" => "224" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Current technologies in vivo diagnosis of cutaneous melanoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S.Q. Wang" 1 => "H. Rabinovitz" 2 => "A.W. Kopf" 3 => "M. 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Preoperative 15-MHz Ultrasound Assessment of Tumor Thickness in Malignant Melanoma

Evaluación de la ecografía cutánea de 15 Mhz en la estimación preoperatoria del espesor tumoral en el melanoma maligno

I. Fernández Canedoa,

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inesbier@gmail.com

Corresponding author.

, M. de Troya Martína, R. Fúnez Liébanab, F. Rivas Ruizc, G. Blanco Egurend, N. Blázquez Sáncheza

a Servicio de Dermatología, Hospital Costa del Sol, Marbella, Málaga, Spain

b Servicio de Anatomía Patológica, Hospital Costa del Sol, Marbella, Málaga, Spain

c Unidad de Investigación, Hospital Costa del Sol, Marbella, Málaga, Spain

d Servicio de Radiología, Hospital Costa del Sol, Marbella, Málaga, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Tumor thickness is of great importance in the management of cutaneous malignant melanoma because it is used to determine the prognosis and is a key factor in planning surgical margins and selecting candidates for sentinel node biopsy&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Breslow depth is the standard measure of tumor thickness in primary cutaneous melanoma&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> A histologic measurement&#44; Breslow depth requires a preoperative excisional skin biopsy and&#44; in addition to being invasive&#44; the procedure may delay definitive surgical treatment because it involves a 2-stage intervention&#46;Cutaneous ultrasound is a noninvasive imaging technique for visualizing the interior layers of the skin&#46; The use of this tool in the field of dermatology has been studied in recent years&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Although the majority of early studies used 20-MHz probes capable of measuring lesions at a depth of 6 to 8<span class="elsevierStyleHsp" style=""></span>mm&#44; many others used lower-resolution probes &#40;10-15<span class="elsevierStyleHsp" style=""></span>MHz&#41; because these were available in most hospitals&#46; However&#44; the current trend is to use higher-resolution probes &#40;75-100<span class="elsevierStyleHsp" style=""></span>MHz&#41;&#44; which measure lesions confined to the epidermis and dermis more accurately&#46; In cutaneous malignant melanoma&#44; cutaneous ultrasound offers the possibility of estimating tumor thickness in vivo&#44; thus avoiding excisional biopsy and speeding up surgical treatment planning&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#8211;5</span></a> Results of recent studies of the validity and utility of cutaneous ultrasound in the management of cutaneous malignant melanoma have been inconsistent&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#8211;12</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The aim of this study was to evaluate cutaneous ultrasound as a tool for measuring tumor thickness in cutaneous malignant melanoma&#46; The histologic variables that affect ultrasound assessment of tumor thickness are also analyzed&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Material and Methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">This retrospective study evaluated the records of a consecutive series of patients with cutaneous malignant melanomas who underwent surgery between 2008 and 2010 in the dermatology department of the Hospital Costa del Sol&#46; In all cases&#44; members of the hospital&#39;s radiology department had performed a preoperative assessment of the lesion using a Toshiba Aplio XG 15-Mhz ultrasound probe to determine tumor thickness&#46; Tumor thickness had been calculated automatically as the maximum vertical distance from the entry echo to the lowest hypoechoic signal&#44; expressed in mm &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The histologic measure of thickness &#40;Breslow depth&#41; had been determined by a pathologist experienced in dermatopathology using an ocular micrometer to measure the maximum distance between the highest level of the stratum granulosum of the epidermis and the deepest point of the tumor&#44; expressed in mm &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The histologic presence of ulceration&#44; regression &#40;absent&#44; &#60; 50&#37;&#44; &#62; 50&#37;&#41;&#44; inflammatory infiltrate &#40;absent&#44; mild&#44; moderate&#44; severe&#41;&#44; and associated nevi had also been recorded&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The study was approved by the ethics committee of Hospital Costa del Sol&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Statistical Analysis</span><p id="par0030" class="elsevierStylePara elsevierViewall">We compared the ultrasound measurement of tumor thickness against the results obtained with the gold standard method &#40;Breslow depth&#41;&#44; using the Pearson correlation coefficient and the intraclass correlation coefficient to quantify the degree of correlation and agreement between the 2 variables&#46; To study the association between histologic variables &#40;ulceration&#44; regression&#44; inflammatory infiltrate&#44; and presence of nevi&#41; and ultrasound assessment of thickness&#44; bivariate analysis was performed&#44; taking as the dependent variable the overestimation of thickness by ultrasound &#40;&#43; 0&#46;1<span class="elsevierStyleHsp" style=""></span>mm&#41; compared with Breslow depth&#44; using &#967;<span class="elsevierStyleSup">2</span> tests and&#44; where appropriate&#44; the Fisher exact test&#46; Statistical significance was set at <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#46; Finally&#44; we studied the sensitivity&#44; specificity&#44; and positive and negative predictive values of cutaneous ultrasound against those of the gold standard for the correct classification of thick melanomas &#40;Breslow depth &#62; 1<span class="elsevierStyleHsp" style=""></span>mm&#41; with a 95&#37; CI&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Results</span><p id="par0035" class="elsevierStylePara elsevierViewall">We studied 79 melanomas from 79 patients &#40;53&#37; of them women&#41; with a mean &#40;SD&#41; age of 56&#46;8 &#40;16&#46;2&#41; years&#59; 42&#37; were located on the trunk&#44; 40&#37; on the limbs&#44; and 18&#37; on the head and neck&#46; Melanomas in situ accounted for 45&#37; of the tumors &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>35&#41; and the remaining 55&#37; were invasive tumors &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>44&#59; 27 melanomas &#8804; 1<span class="elsevierStyleHsp" style=""></span>mm&#44; 17 melanomas &#62; 1<span class="elsevierStyleHsp" style=""></span>mm&#41;&#46; The mean Breslow depth of the series was 0&#46;8 &#40;1&#46;4&#41; mm&#46; The mean thickness as measured by ultrasound was 1&#46;2 &#40;1&#46;7&#41; mm&#46; The histologic findings are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">The Pearson correlation coefficient between ultrasound assessment of thickness and Breslow depth was 0&#46;678 &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; The value of the intraclass correlation coefficient measuring agreement between the ultrasound assessment of thickness and Breslow depth was 0&#46;78 &#40;95&#37; CI&#44; 0&#46;61-0&#46;88&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Bivariate analysis showed that ultrasound tended to overestimate tumor thickness in the presence of moderate to severe inflammatory infiltrate and nevi&#44; though this tendency was not statistically significant &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Classic sensitivity tests showed that the sensitivity of ultrasound for the diagnosis of thick melanomas &#40;Breslow depth &#62; 1<span class="elsevierStyleHsp" style=""></span>mm&#41; was 82&#37;&#44; specificity was 80&#37;&#44; and positive and negative predictive values were 54&#37; and 94&#37;&#44; respectively &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0055" class="elsevierStylePara elsevierViewall">In this study we analyzed the accuracy of cutaneous ultrasound as a tool for measuring tumor thickness in a consecutive series of 79 primary melanomas&#46; Of interest is the high proportion of minimally invasive melanomas in situ&#44; a finding that we attribute to the systematic use of dermoscopy in the diagnosis of pigmented skin lesions and to the continuous application of primary prevention strategies in our population&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">We found moderate correlation and agreement between ultrasound and histologic measures&#44; whereas most earlier studies<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#8211;10</span></a> have reported good correlation&#46; Tacke et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> using a 20-MHz probe on a series of 259 melanomas&#44; reported a correlation coefficient of 0&#46;88 &#40;lesions of 0&#46;55 to 0&#46;95<span class="elsevierStyleHsp" style=""></span>mm were classified incorrectly by ultrasound in 34&#37; of cases and lesions of 1&#46;30 to 1&#46;70<span class="elsevierStyleHsp" style=""></span>mm were classified incorrectly in 50&#37; of cases&#41;&#46; Conversely&#44; Serrone et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> using a 20-MHz probe on a series of 261 lesions&#44; reported a correlation coefficient of 0&#46;95 in melanomas larger than 1&#46;51<span class="elsevierStyleHsp" style=""></span>mm&#44; finding the lowest correlation in lesions smaller than 0&#46;75<span class="elsevierStyleHsp" style=""></span>mm&#46; The results reported by Kaikaris et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> using a 14-MHz probe&#44; were similar &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;283 in melanomas of 1&#8211;2<span class="elsevierStyleHsp" style=""></span>mm and <span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;869 in melanomas larger than 2<span class="elsevierStyleHsp" style=""></span>mm&#41;&#46; Many factors make comparison between studies difficult&#44; including the use of diverse probes&#44; differences between the series studied&#44; the inclusion of benign lesions &#40;mainly nevi&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> and the exclusion of in situ lesions<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> in the belief that ultrasound does not visualize epidermal lesions&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Some histologic features of tumors may alter the ultrasound assessment of thickness&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Hoffman et al&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> found that the cause of 80&#37; of cases of overestimation was the presence of inflammatory infiltrate&#46; In our series&#44; cutaneous ultrasound tended to overestimate tumor thickness in comparison with the histologic measure in the presence of moderate to severe inflammatory infiltrate and associated nevi&#44; though no statistical significance was found &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41;&#46; These histologic features act as artifacts and interfere with the ultrasound assessment of the tumor because cutaneous ultrasound does not differentiate between tumor cells and inflammatory or nevus cells&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The sensitivity&#44; specificity&#44; and positive and negative predictive values for the diagnosis of thick melanomas &#40;&#62;1<span class="elsevierStyleHsp" style=""></span>mm&#41; were 82&#37;&#44; 80&#37;&#44; 54&#37;&#44; and 94&#37;&#44; respectively&#46; These results suggest that cutaneous ultrasound would properly stage the tumor and allow a single surgical intervention to be planned in approximately 80&#37; of melanomas&#46; However&#44; it would not provide an accurate measurement on which to base a therapeutic decision in 20&#37; of melanomas&#46; Cutaneous ultrasound showed high discriminatory capacity for thin melanomas but was less successful at discriminating thick melanomas&#46; Some authors have developed diagnostic algorithms that increase the diagnostic accuracy for thick melanomas by combining clinical&#44; dermoscopic&#44; and ultrasound findings&#44; reaching a sensitivity of 97&#37; and a specificity of 100&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Almost half the melanomas assessed by ultrasound as thick were in fact thin &#40;&#60; 1<span class="elsevierStyleHsp" style=""></span>mm&#41;&#46; This finding is explained by the frequent association of inflammatory infiltrate and nevi with the melanomas in our series&#46; This tendency towards overestimation can be remedied by using higher-frequency probes&#44; which have a higher resolution&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">The results of one study&#44; in line with our findings&#44; showed a particularly good correspondence between ultrasound and histologic measurements using a 30-MHz probe when the lesions were smaller than 1<span class="elsevierStyleHsp" style=""></span>mm in a series of 68 melanomas and an even better correspondence in lesions on the sole &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;945&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> In contrast&#44; Machet et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> using a 20-MHz probe&#44; found lesions on the sole to be difficult to measure because of the thickness of the stratum corneum&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">In the ultrasound estimation of tumor thickness our results contrast with those published in a recent prospective study of 54 cutaneous malignant melanomas&#44; which reported sensitivity&#44; specificity&#44; and positive and negative predictive values in the diagnosis of thick melanomas &#40;&#62; 1<span class="elsevierStyleHsp" style=""></span>mm&#41; of 86&#37;&#44; 97&#37;&#44; 95&#37;&#44; and 91&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> The diagnostic accuracy of cutaneous ultrasound in that study was striking despite the lower ultrasound resolution of the probe used by the authors &#40;10 Mhz&#41;&#46; These results could be explained by the high proportion of melanomas later found to be thick on histology&#44; which would be more accurately measured by ultrasound assessment because the presence of other histologic factors would not alter their ultrasound assessment as thick melanomas&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">The present study had several limitations&#46; The small size of our series made it difficult to interpret the results with regard to the influence of histologic findings on the ultrasound assessment of thickness&#44; so it was not possible to establish causal relationships between histologic and ultrasound findings&#46; Interpersonal variability may interfere in the ultrasound assessment of tumor thickness&#44; though the use of standardized procedure minimizes this bias&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Technological advances in ultrasound&#44; such as the use of contrast agents&#44;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> and the incorporation of new in vivo microscopy techniques&#44; including dermoscopy<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;18</span></a> and confocal microscopy&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> are encouraging and their combined use will improve the preoperative diagnosis of melanoma in the near future&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">In conclusion&#44; cutaneous ultrasound is a tool of great interest in the preoperative study of cutaneous malignant melanoma&#46; It identifies thin melanomas fairly accurately and can be useful for planning appropriate surgical margins&#46; Further studies are necessary to confirm whether certain histologic characteristics of the tumor&#44; such as the presence of moderate to severe inflammatory infiltrate and associated nevi&#44; can lead to an overestimation of thickness by ultrasound&#44; limiting the clinical utility of this imaging technique in the management of cutaneous malignant melanoma&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Ethical Considerations</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Protection of persons and animals</span><p id="par0105" class="elsevierStylePara elsevierViewall">The authors state that no experiments on humans or animals were performed in this study&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Data confidentiality</span><p id="par0110" class="elsevierStylePara elsevierViewall">The authors state that no patient data appear in this article&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Right to privacy and informed consent</span><p id="par0115" class="elsevierStylePara elsevierViewall">The authors state that no patient data appear in this article&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of interest</span><p id="par0120" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span></span>"
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        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Tumor thickness is of great importance in the management of cutaneous malignant melanoma &#40;MM&#41;&#58; this variable not only affects prognosis but is also a key factor in planning surgical margins and selecting candidates for sentinel node biopsy&#46; Breslow depth is the standard histologic measure of thickness&#44; but technological advances have provided imaging techniques such as cutaneous ultrasound that can potentially assess tumor thickness and enable prompt initiation of definitive treatment&#46;</p> <span class="elsevierStyleSectionTitle">Objectives</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">a&#41;</span> To evaluate the utility of ultrasound assessment of tumor thickness in MM&#44; and <span class="elsevierStyleItalic">b&#41;</span> to analyze histologic variables that affect ultrasound assessments of thickness&#46;</p> <span class="elsevierStyleSectionTitle">Materials and methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Retrospective study of a consecutive series of 79 primary cutaneous MMs in which tumor thickness had been assessed by 15-MHz ultrasound before surgery&#46; We gathered data from histology reports&#44; studying Breslow depth and the presence of ulceration&#44; regression&#44; inflammatory infiltrate&#44; and associated nevi&#46; Correlation coefficients were calculated to evaluate the strength of association between Breslow depth and thickness assessed by ultrasound&#46; We also calculated the sensitivity&#44; specificity&#44; and positive and negative predictive values of ultrasound measurement in the diagnosis of MMs more than 1<span class="elsevierStyleHsp" style=""></span>mm thick&#46; Associations between histologic variables and the overestimation of thickness by ultrasound were also analyzed&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The 79 primary MMs studied had a mean &#40;SD&#41; Breslow depth of 0&#46;8 &#40;1&#46;4&#41; mm&#46; There was moderate correlation and agreement between Breslow depth and the ultrasound assessment of thickness &#40;Pearson correlation coefficient&#44; 0&#46;678&#59; intraclass correlation coefficient&#44; 0&#46;78&#41;&#46; The tendency of ultrasound to overestimate thickness was nonsignificantly related to the presence of a moderate to intense infiltrate and associated nevi &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41;&#46; The sensitivity of ultrasound for the diagnosis of MM over 1<span class="elsevierStyleHsp" style=""></span>mm thick was 82&#37;&#59; specificity was 80&#37;&#44; and positive and negative predictive values were 54&#37; and 94&#37;&#44; respectively&#46;</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Ultrasound imaging quite correctly identifies thin MMs and can be useful for planning adequate surgical margins&#59; however&#44; there are limitations on its usefulness in the diagnosis of thick MMs&#46; Additional studies are required to confirm whether certain histologic characteristics&#44; such as the presence of a moderate to intense inflammatory infiltrate or associated nevi can lead to overestimation of thickness by ultrasound&#44; limiting the clinical utility of this imaging technique in MM management&#46;</p>"
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        "resumen" => "<span class="elsevierStyleSectionTitle">Introducci&#243;n</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">El espesor tumoral es una variable de gran trascendencia en el manejo cl&#237;nico del melanoma maligno cut&#225;neo &#40;MMC&#41;&#44; ya que no solo establece el pron&#243;stico&#44; sino que adem&#225;s determina la planificaci&#243;n de m&#225;rgenes quir&#250;rgicos y selecciona a aquellos pacientes candidatos a biopsia selectiva de ganglio centinela&#46; El &#237;ndice de Breslow &#40;IB&#41; es el procedimiento histom&#233;trico est&#225;ndar para la determinaci&#243;n del espesor tumoral del melanoma&#46; El desarrollo de t&#233;cnicas de imagen&#44; como la ecograf&#237;a cut&#225;nea &#40;EC&#41;&#44; plantea la posibilidad de realizar una estimaci&#243;n no invasiva que agiliza la instauraci&#243;n del tratamiento definitivo&#46;</p> <span class="elsevierStyleSectionTitle">Objetivos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">a&#41;</span> Evaluar la EC como instrumento de medici&#243;n del espesor tumoral en el MMC&#44; y <span class="elsevierStyleItalic">b&#41;</span> analizar los factores histol&#243;gicos que influyen en la estimaci&#243;n del espesor ecogr&#225;fico&#46;</p> <span class="elsevierStyleSectionTitle">Material y m&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Estudio retrospectivo de una serie consecutiva de 79 melanomas cut&#225;neos primarios&#46; En todos los casos&#44; se practic&#243; un estudio ecogr&#225;fico preoperatorio con una sonda de 15 Mhz para la determinaci&#243;n del espesor tumoral &#40;EE&#41;&#46; Se analizaron los ex&#225;menes histol&#243;gicos&#44; estudi&#225;ndose el IB&#44; adem&#225;s de la presencia de ulceraci&#243;n&#44; regresi&#243;n&#44; infiltrado inflamatorio y nevus&#46; Se estudian el grado de correlaci&#243;n y el nivel de concordancia entre los valores de EE e IB&#46; Se estiman la sensibilidad&#44; la especificidad y los valores predictivos de la EC en el diagn&#243;stico de melanomas de espesor &#62;<span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>mm&#46; Se analiza la relaci&#243;n de las variables histol&#243;gicas en la determinaci&#243;n del EE&#46;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Se estudian 79 melanomas primarios&#44; IB medio&#58; 0&#46;8<span class="elsevierStyleHsp" style=""></span>mm &#40;DE&#58; 1&#44;4&#41;&#46; La EC evidenci&#243; un grado de correlaci&#243;n y un nivel de concordancia moderado con respecto al IB &#40;coeficiente de correlaci&#243;n de Pearson&#58; 0&#46;678&#44; coeficiente de correlaci&#243;n intraclase&#58; 0&#46;78&#44; respectivamente&#41;&#46; La EC mostr&#243; tendencia a sobrestimar el espesor histol&#243;gico en relaci&#243;n con la presencia de infiltrado inflamatorio moderado-intenso y nevus&#44; sin alcanzar significaci&#243;n estad&#237;stica &#40;p<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; La EC mostr&#243; valores de sensibilidad y especificidad&#44; y valores predictivos positivo y negativo para el diagn&#243;stico de melanomas gruesos &#40;&#62;<span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>mm&#41; del 82&#44; el 80&#44; el 54 y el 94&#37;&#44; respectivamente&#46;</p> <span class="elsevierStyleSectionTitle">Conclusi&#243;n</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">La EC permite discriminar con bastante precisi&#243;n melanomas finos y planificar m&#225;rgenes quir&#250;rgicos adecuados&#44; pero presenta limitaciones para el diagn&#243;stico de melanomas gruesos&#46; Son necesarios m&#225;s estudios para confirmar si determinadas caracter&#237;sticas histol&#243;gicas del tumor&#44; como la presencia de infiltrado inflamatorio moderado-intenso y nevus&#44; pueden condicionar una sobrestimaci&#243;n del espesor ecogr&#225;fico&#44; limitando su aplicabilidad cl&#237;nica en el manejo del MMC&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara">Please cite this article as&#58; Fern&#225;ndez Canedo I&#44; et al&#46; Evaluaci&#243;n de la ecograf&#237;a cut&#225;nea de 15 Mhz en la estimaci&#243;n preoperatoria del espesor tumoral en el melanoma maligno&#46; Actas Dermosifiliogr&#46; 2013&#59;104&#58;227&#8211;31&#46;</p>"
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Associated nevus&#58; yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                  \t\t\t\t\tvoid\n
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                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">No Overestimation</td><td class="td" title="\n
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                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Overestimation &#40;&#43; 0&#46;1 mm&#41;</td><td class="td" title="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">80&#46;0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#60; 50&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">58&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">41&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#62; 50&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Ulceration</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#46;23&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Absent-mild&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">65&#46;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Moderate-severe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Associated nevus</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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Article information

ISSN: 15782190
Original language: English

DOI:10.1016/j.adengl.2012.06.025

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Year/Month	Html	Pdf	Total

2024 November	8	8	16
2024 October	63	42	105
2024 September	74	34	108
2024 August	95	68	163
2024 July	75	40	115
2024 June	96	37	133
2024 May	68	30	98
2024 April	78	35	113
2024 March	69	26	95
2024 February	59	26	85
2024 January	73	46	119
2023 December	43	33	76
2023 November	68	35	103
2023 October	79	48	127
2023 September	64	36	100
2023 August	37	23	60
2023 July	53	45	98
2023 June	49	31	80
2023 May	38	25	63
2023 April	38	22	60
2023 March	46	28	74
2023 February	52	29	81
2023 January	38	34	72
2022 December	55	38	93
2022 November	38	31	69
2022 October	32	43	75
2022 September	36	48	84
2022 August	41	38	79
2022 July	31	45	76
2022 June	31	26	57
2022 May	38	47	85
2022 April	41	40	81
2022 March	58	61	119
2022 February	36	27	63
2022 January	40	43	83
2021 December	34	39	73
2021 November	37	38	75
2021 October	66	60	126
2021 September	44	47	91
2021 August	35	35	70
2021 July	34	38	72
2021 June	32	31	63
2021 May	39	39	78
2021 April	107	90	197
2021 March	60	25	85
2021 February	55	29	84
2021 January	34	21	55
2020 December	39	14	53
2020 November	28	19	47
2020 October	29	13	42
2020 September	38	9	47
2020 August	18	21	39
2020 July	34	17	51
2020 June	36	28	64
2020 May	36	16	52
2020 April	38	23	61
2020 March	40	17	57
2020 February	0	1	1
2020 January	0	3	3
2019 December	4	2	6
2019 November	0	1	1
2019 October	1	1	2
2019 September	10	0	10
2019 July	0	7	7
2019 June	0	9	9
2019 May	3	34	37
2019 April	0	22	22
2019 March	0	9	9
2019 February	2	5	7
2019 January	0	4	4
2018 November	2	0	2
2018 September	2	0	2
2018 February	35	7	42
2018 January	29	11	40
2017 December	48	10	58
2017 November	45	11	56
2017 October	42	10	52
2017 September	19	7	26
2017 August	31	6	37
2017 July	32	14	46
2017 June	56	21	77
2017 May	51	13	64
2017 April	45	20	65
2017 March	45	24	69
2017 February	22	10	32
2017 January	57	11	68
2016 December	54	8	62
2016 November	46	12	58
2016 October	65	10	75
2016 September	50	17	67
2016 August	54	13	67
2016 July	31	16	47
2016 June	7	13	20
2016 May	9	17	26
2016 April	7	2	9
2016 March	6	3	9
2016 February	4	1	5
2016 January	11	3	14
2015 December	6	0	6
2015 November	11	1	12
2015 October	7	1	8
2015 September	8	1	9
2015 August	9	1	10
2015 July	68	119	187
2015 June	68	11	79
2015 May	82	31	113
2015 April	61	17	78
2015 March	28	1	29
2015 February	20	4	24
2015 January	14	2	16
2014 December	26	5	31
2014 November	14	5	19
2014 October	24	2	26
2014 September	16	1	17
2014 August	17	6	23
2014 July	21	3	24
2014 June	24	2	26
2014 May	22	6	28
2014 April	31	5	36
2014 March	26	9	35
2014 February	19	4	23
2014 January	18	5	23
2013 December	27	12	39
2013 November	23	4	27
2013 October	23	8	31
2013 September	5	3	8
2013 August	8	2	10
2013 July	3	2	5
2013 June	2	6	8
2013 May	0	2	2
2013 April	2	2	4

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