Original article
Effect of Imiquimod as Compared With Surgery on the Cancerization Field in Basal Cell carcinoma
Efecto del imiquimod comparado con la cirugía sobre el campo de cancerización en el carcinoma basocelular
J. Graells
, R.M. Ojeda, A. García-Cruz
Autor para correspondencia
Servei de Dermatologia, Parc Sanitari Sant Joan de Déu, Sant Boi de Llobregat, Barcelona, Spain
Leído
5414
Vecesse ha leído el artículo
1896
Total PDF
3518
Total HTML
Compartir estadísticas
array:24 [ "pii" => "S1578219013002692" "issn" => "15782190" "doi" => "10.1016/j.adengl.2013.09.001" "estado" => "S300" "fechaPublicacion" => "2014-01-01" "aid" => "892" "copyright" => "Elsevier España, S.L. and AEDV" "copyrightAnyo" => "2013" "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Actas Dermosifiliogr. 2014;105:53-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1571 "formatos" => array:3 [ "EPUB" => 43 "HTML" => 1241 "PDF" => 287 ] ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0001731013003207" "issn" => "00017310" "doi" => "10.1016/j.ad.2013.09.001" "estado" => "S300" "fechaPublicacion" => "2014-01-01" "aid" => "892" "copyright" => "Elsevier España, S.L. and AEDV" "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Actas Dermosifiliogr. 2014;105:53-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2401 "formatos" => array:3 [ "EPUB" => 2 "HTML" => 1616 "PDF" => 783 ] ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original</span>" "titulo" => "Efecto del imiquimod comparado con la cirugía sobre el campo de cancerización en el carcinoma basocelular" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "53" "paginaFinal" => "59" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Effect of Imiquimod as Compared With Surgery on the Cancerization Field in Basal cell carcinoma" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1831 "Ancho" => 1666 "Tamanyo" => 95923 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Curva de supervivencia (Kaplan-Meier) comparando la aparición de un segundo CB tras tratamiento del primer tumor con cirugía versus imiquimod.</p> <p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">CB: carcinoma basocelular.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J. Graells, R.M. Ojeda, A. García-Cruz" "autores" => array:3 [ 0 => array:2 [ "nombre" => "J." "apellidos" => "Graells" ] 1 => array:2 [ "nombre" => "R.M." "apellidos" => "Ojeda" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "García-Cruz" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S1578219013002692" "doi" => "10.1016/j.adengl.2013.09.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219013002692?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731013003207?idApp=UINPBA000044" "url" => "/00017310/0000010500000001/v1_201401250106/S0001731013003207/v1_201401250106/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S1578219013002709" "issn" => "15782190" "doi" => "10.1016/j.adengl.2013.07.002" "estado" => "S300" "fechaPublicacion" => "2014-01-01" "aid" => "878" "copyright" => "Elsevier España, S.L. and AEDV" "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Actas Dermosifiliogr. 2014;105:60-8" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2270 "formatos" => array:3 [ "EPUB" => 45 "HTML" => 1935 "PDF" => 290 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Sentinel Lymph Node Status in Melanoma: Prognostic Value in a Tertiary Hospital and Correlation with Mitotic Activity" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "60" "paginaFinal" => "68" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Biopsia de ganglio centinela en melanoma. Valor pronóstico y correlación con el índice mitótico. Experiencia en un hospital terciario" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "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" => 2340 "Ancho" => 2337 "Tamanyo" => 317126 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Study population. SLN indicates sentinel lymph node.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "L. Mahiques Santos, V. Oliver Martinez, V. Alegre de Miquel" "autores" => array:3 [ 0 => array:2 [ "nombre" => "L." "apellidos" => "Mahiques Santos" ] 1 => array:2 [ "nombre" => "V." "apellidos" => "Oliver Martinez" ] 2 => array:2 [ "nombre" => "V." "apellidos" => "Alegre de Miquel" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0001731013002780" "doi" => "10.1016/j.ad.2013.07.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731013002780?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219013002709?idApp=UINPBA000044" "url" => "/15782190/0000010500000001/v1_201401220123/S1578219013002709/v1_201401220123/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1578219013002680" "issn" => "15782190" "doi" => "10.1016/j.adengl.2013.06.003" "estado" => "S300" "fechaPublicacion" => "2014-01-01" "aid" => "871" "copyright" => "Elsevier España, S.L. and AEDV" "documento" => "article" "crossmark" => 0 "subdocumento" => "ssu" "cita" => "Actas Dermosifiliogr. 2014;105:45-52" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 3485 "formatos" => array:3 [ "EPUB" => 43 "HTML" => 2629 "PDF" => 813 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Novelties in Dermatology</span>" "titulo" => "Omalizumab in the Treatment of Chronic Urticaria" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "45" "paginaFinal" => "52" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Omalizumab en el tratamiento de la urticaria crónica" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "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" => 1170 "Ancho" => 3170 "Tamanyo" => 215431 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Treatment algorithm recommended in the EAACI/GA2LEN/EDF/WAO guideline.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "L. Francés, M. Leiva-Salinas, J.F. Silvestre" "autores" => array:3 [ 0 => array:2 [ "nombre" => "L." "apellidos" => "Francés" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Leiva-Salinas" ] 2 => array:2 [ "nombre" => "J.F." "apellidos" => "Silvestre" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0001731013002603" "doi" => "10.1016/j.ad.2013.06.002" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731013002603?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219013002680?idApp=UINPBA000044" "url" => "/15782190/0000010500000001/v1_201401220123/S1578219013002680/v1_201401220123/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Effect of Imiquimod as Compared With Surgery on the Cancerization Field in Basal Cell carcinoma" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "53" "paginaFinal" => "59" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "J. Graells, R.M. Ojeda, A. García-Cruz" "autores" => array:3 [ 0 => array:4 [ "nombre" => "J." "apellidos" => "Graells" "email" => array:1 [ 0 => "jordi.graells@pssjd.org" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "R.M." "apellidos" => "Ojeda" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "García-Cruz" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servei de Dermatologia, Parc Sanitari Sant Joan de Déu, Sant Boi de Llobregat, Barcelona, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Efecto del imiquimod comparado con la cirugía sobre el campo de cancerización en el carcinoma basocelular" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 3331 "Ancho" => 3000 "Tamanyo" => 325964 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Survival curves (Kaplan-Meier) showing the development of a second basal cell carcinoma (BCC) in different cancerization fields in patients with an initial BCC treated with surgery or imiquimod. A, Local; B, Lymphatic; C, Regional; D, Outside the cancerization field.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Basal cell carcinoma is the most common tumor in humans and its incidence has risen dramatically worldwide in recent decades.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Patients who have had BCC have a greater chance of developing subsequent BCCs, with the risk of a second BCC estimated at between 22% and 50%.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2–5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Sun exposure is the main risk factor for skin cancer. The likelihood of a subsequent BCC developing at the site of a previous BCC and in the surrounding area is theoretically very similar as both areas have been subjected to a similar degree of sun damage. This concept is known as <span class="elsevierStyleItalic">field cancerization</span> and has been described in many epithelial tumors.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6–8</span></a> Whether or not it also applies to BCC, however, is still a matter of debate.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Surgery is the treatment of choice for BCC. Other alternatives include local immunotherapy, which can cure BCC by stimulating a local immune response. One local immune response modifier is topical imiquimod 5%, which has been licensed for the treatment of small superficial BCCs in adults and has a cure rate of between 43% and 100%.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Imiquimod exerts its effect as a topical immunomodulator by activating both the innate and acquired immune systems.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,11</span></a> It has been shown to have an effect on the cancerization field in actinic keratosis.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In this retrospective study we investigated the ability of imiquimod, when it is used to treat BCC, to prevent the development of second BCCs in the area treated, in the cancerization field, and beyond this field.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Material and Methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">The study was conducted in a secondary care level hospital serving a predominantly urban population of approximately 130 000 inhabitants.</p><p id="par0035" class="elsevierStylePara elsevierViewall">We retrospectively compared 2 groups of patients with histologically confirmed BCC treated with either surgery or imiquimod. We reviewed the charts of patients treated for their first BCC at our hospital between January 2003 and December 2011 and recorded the date and type of treatment (surgery vs imiquimod). Due to the retrospective design of the study, we were unable to systematically record why the treating physician decided to choose one treatment over the other. The treatment regimen for imiquimod was 5 days a week for 6 weeks in all cases.</p><p id="par0040" class="elsevierStylePara elsevierViewall">We also made note of the main variables that can influence the occurrence of subsequent BCCs based on the findings of previous studies, namely, age, sex, number of previous BCCs, and number of simultaneous BCCs. The follow-up data recorded included, where applicable, the date at which a second BCC was histologically confirmed; the proximity of the second BCC to the first one (local, same lymphatic drainage basin, same anatomic region, other); and the duration of follow-up (to diagnosis of the second BCC, discharge from care, last routine checkup, or loss to follow-up). The follow-up period analyzed was 60 months and patients followed for less than 3 months were excluded. BCCs diagnosed within 3 months of the first tumor were considered to be synchronous. Recurrent tumors were not classified as second BCCs.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Three levels of cancerization field were defined: local, lymphatic, and regional. The field was defined as local when the second tumor occurred within 5<span class="elsevierStyleHsp" style=""></span>cm of the first one, lymphatic when the first and second tumors occurred in the same lymphatic drainage basin, and regional, when the 2 tumors occurred in the same anatomic region (head and neck, anterior thorax, posterior thorax, abdomen, lumbar region, upper limbs and lower limbs). Second BCCs not in the same anatomic region as the first BCC were deemed to be outside the cancerization field.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Imiquimod-induced inflammation was classified as mild (not requiring any change in treatment), moderate (requiring the addition of a corticosteroid-antibiotic cream but no change in imiquimod treatment), or intense (requiring the temporary or permanent withdrawal of treatment).</p><p id="par0055" class="elsevierStylePara elsevierViewall">Data were analyzed using the Kaplan-Meier survival method for the estimation of risk; the event of interest was histologic confirmation of a second BCC. The Cox proportional hazards model was used to estimate the influence of variables. The χ<span class="elsevierStyleSup">2</span> test and the Fisher exact test were used to compare categorical data. Statistical significance was set at a <span class="elsevierStyleItalic">P</span> value of .05. Data were analyzed using the SPSS statistical package (SPSS Inc), version 19 for Windows.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><p id="par0060" class="elsevierStylePara elsevierViewall">We reviewed the charts of 623 patients with histologically confirmed BCC (349 men and 274 women). The mean (SD) age was 67.8 (12.9) years.</p><p id="par0065" class="elsevierStylePara elsevierViewall">The majority of BCCs (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>484) were located on the head and neck, followed by the trunk (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>101), and the limbs (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>37). The site of 1 of the tumors was not recorded. The treatment of choice was surgery for 550 tumors (88.3%), imiquimod for 71 tumors (11.4%), and cryotherapy for 2. The baseline characteristics of the patients are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Of the 71 BCCs treated with imiquimod, 34 were superficial, 22 were infiltrating, 1 was nodular, and 14 were of an unspecified histologic subtype. The cure rate was 85.9% (61 of 71 tumors). Ten tumors required complementary surgery. Three of these were superficial, 5 were infiltrating, and 2 were of an unknown subtype. One infiltrating BCC recurred at 3 years. The cure rate was 91% for superficial BCC (31 of 34 tumors) and 72% for infiltrating BCC (16 of 22 tumors).</p><p id="par0075" class="elsevierStylePara elsevierViewall">In total, 227 (36.4%) of the 623 patients developed a second BCC. The rate of occurrence of a second BCC was 38.2% in the surgery group (210 of 550 patients) and 23.9% in the imiquimod group (17 of 71 patients, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">.</span>02).</p><p id="par0080" class="elsevierStylePara elsevierViewall">In <a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>, the Kaplan-Meier survival curves show the risk of a second BCC according to whether patients were treated with surgery or imiquimod. Univariate analysis, with treatment type as the dependent variable, showed that surgery was associated with a significantly higher risk of a second BCC (hazard ratio [HR], 2.16; 95% CI, 1.31-3.59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">.</span>0026) than imiquimod. The following variables were included in the multivariate analysis: type of treatment (surgery vs imiquimod), age, sex, a past history of multiple BCCs (≥3), and current multiple BCCs (≥3). As shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>, this analysis showed significant associations between an increased risk of a second BCC and older age, male sex, previous multiple BCCs, and treatment with surgery (HR, 2.13; 95% CI, 1.28-3.53; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">.</span>0032).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Of the 396 patients who did not experience the event (a second BCC) in our series (63.6%), 29 were event-free at the time of discharge, 300 were in follow-up at the time of the chart review, and 67 (10.7% of the whole group) had been lost to follow-up.</p><p id="par0090" class="elsevierStylePara elsevierViewall">The analysis was repeated with a subgroup of patients who had only superficial BCC in order to create 2 comparable groups in terms of the indication of imiquimod in the summary of product characteristics (SPC). The survival curves obtained for the subgroup (data not shown) were practically identical to those found for the whole group and surgery was still associated with a higher risk of a second BCC (HR, 2.17). In this group, however, the difference was not significant (95% CI, 0.82-5.75; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.11), probably owing to the small sample size. We did find significant differences when the imiquimod group as a whole was compared with the subgroup of patients with superficial BCC who underwent surgery (HR, 2.21; 95% CI, 1.22-3.99; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.008).</p><p id="par0095" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a> shows the survival curves for patients stratified by surgery and imiquimod treatment who developed a second BCC in the local, lymphatic, and regional cancerization fields (A-C) and outside the cancerization field of the first tumor (D). The univariate analysis showed significant differences in the lymphatic and regional fields, and also showed a tendency towards a protective effect of imiquimod on the local cancerization field. No significant difference in the risk of a second BCC outside the cancerization field was observed between the surgery and the imiquimod groups (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">Most of the second BCCs (73% in the surgery group and 47% in the imiquimod group) occurred within 2 years of diagnosis of the first tumor. We examined the timing of the protective effect of imiquimod on the risk of a second BCC. We found that imiquimod tended to exert a protective effect at 12 and 24 months after the first BCC (8.5% of second BCCs vs 15.2% in the surgery group at 12 months and 2.8% vs 10% at 24 months; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.049). At later dates, no differences were found, although the data were limited by the small number of cases.</p><p id="par0105" class="elsevierStylePara elsevierViewall">We also analyzed whether the degree of inflammation induced by imiquimod influenced the risk of a second BCC and found no differences between patients with mild (incidence of second BCCs,27.3%), moderate (20.7%), or intense (22.2%) inflammation (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.127).</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discussion</span><p id="par0110" class="elsevierStylePara elsevierViewall">We found that, compared with surgery, imiquimod exerts an effect on the cancerization field in the treatment of BCC. Patients treated surgically had a higher risk of developing a second BCC than those treated with imiquimod, with a HR of 2.16 (95% CI, 1.31-3.59) in the univariate analysis and of 2.13 (95% CI, 1.28-3.53) in the multivariate analysis.</p><p id="par0115" class="elsevierStylePara elsevierViewall">As expected, older age, male sex, and a history of multiple BCCs, all factors identified as risk factors for subsequent BCCs in previous studies, also had a significant effect on the risk of a second BCC.</p><p id="par0120" class="elsevierStylePara elsevierViewall">There have been reports of imiquimod exerting an effect on the cancerization field in actinic keratosis,<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,8</span></a> but with the exception of 1 case report,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> we found no such reports for BCC.</p><p id="par0125" class="elsevierStylePara elsevierViewall">Imiquimod stimulates innate and cell-mediated immunity through the toll-like receptor 7 pathway<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> and induces apoptosis of neoplastic cells in BCC. It promotes the secretion of cytokines at the application site, the mobilization and activation of plasmacytoid dendritic cells, the mobilization and activation of Langerhans cells in the lymph nodes, the activation of specific cytotoxic T cells, and the accumulation of tumoricidal cells in the treated area.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">While imiquimod acts mainly at the local level, there is evidence that its effects extend beyond the application site.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Serum concentrations of imiquimod have been detected following topical use,<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> and several articles have reported systemic effects after the administration of topical imiquimod.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16,17</span></a> In our practice, we have also seen some cases of flu-like symptoms in patients treated with imiquimod.</p><p id="par0135" class="elsevierStylePara elsevierViewall">UV radiation not only acts at the level of the skin but also exerts immunosuppressive effects on the lymph nodes, impairing the antigen-presenting function of Langerhans cells.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> This could induce a cancerization field effect beyond the area directly irradiated by the UV rays. Furthermore, the mechanistic action of imiquimod on the lymph nodes would explain why its effect extends beyond the cancerization field. We hypothesize that the cancerization effect of imiquimod is not only local, but also regional and lymphatic. Akkilic-Materna et al.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> introduced the concept of lymphatic cancerization field in a report of a patient in whom topical imiquimod used to treat actinic keratosis cured a BCC in the same lymphatic region.</p><p id="par0140" class="elsevierStylePara elsevierViewall">In our study, imiquimod had an effect not only on the local cancerization field but also on the regional and lymphatic fields. Although the differences in the local cancerization field were not significant, we did observe a clear tendency towards a protective effect of imiquimod, which would probably have reached statistical significance if more patients had been treated with this immunomodulator. It is well known that patterns of lymphatic drainage vary greatly from one patient to another, and this is a limitation for retrospective evaluation. However, the results observed for the effect of imiquimod on the lymphatic cancerization field in our series are very similar to those seen for the regional field, which is much easier to define, even retrospectively. Our findings suggest that imiquimod treatment may reduce the risk of a second BCC in the cancerization field where it is applied and in the corresponding lymphatic drainage basin and anatomic region. If our hypothesis is correct, the concept of cancerization field could be extended to include areas outside the immediate area around the primary tumor.</p><p id="par0145" class="elsevierStylePara elsevierViewall">A clearance rate of 61% to 73% at 12 months has been reported for imiquimod in the treatment of actinic keratosis.<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20,21</span></a> In our series, the rate of second BCCs was lower with imiquimod than with surgery at 12 and 24 months, and the difference reached statistical significance in the second year. This finding is important, as 73% of second BCCs in the surgery group occurred within 2 years of the operation. Imiquimod could, therefore, offer an additional benefit by reducing the risk of a second BCC during the period when this risk is highest. Other studies have shown that second BCCs frequently appear within a year of diagnosis of the first tumor.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">According to the SPC, imiquimod is not indicated for the treatment of infiltrating BCC. In our series, however, a considerable number of infiltrating BCCs (n<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">=</span><span class="elsevierStyleHsp" style=""></span>22) were treated with imiquimod. The use of this drug in clinical practice may be seen as an opportunity to avoid aggressive surgery, by eliminating the tumor or at least reducing its size, regardless of whether it is superficial or infiltrating. Furthermore, not all patients who receive imiquimod undergo biopsy,<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> so it is likely that some tumors thought to be superficial are actually infiltrating. In addition, depending on the area sampled, infiltrating BCCs may be diagnosed as superficial on biopsy.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">In our series, imiquimod achieved a cure rate (no recurrences or need for complementary surgery) of 84.5% (91% for superficial BCCs and 72% for infiltrating BCCs). These percentages are similar to those published elsewhere.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,11,22</span></a> The median follow-up time in our study for patients treated with imiquimod was 32.9 months, and there was just 1 recurrence, at 3 years. The finding is interesting as there is a shortage of studies of imiquimod with long follow-up periods.</p><p id="par0160" class="elsevierStylePara elsevierViewall">Patients with BCC have a high risk of developing second and subsequent BCCs, and because nonmelanoma skin cancer is being increasingly viewed as a chronic disease,<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> strategies are needed to lower the incidence of new tumors. Some authors argue that the development of subsequent BCCs is unaffected by the application of preventive measures.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,25</span></a> Patients must, therefore, be monitored over a long period, although the duration of follow-up will obviously vary from case to case.</p><p id="par0165" class="elsevierStylePara elsevierViewall">Our results support the use of imiquimod in the treatment of superficial BCC and suggest that this drug has the added benefit of reducing the incidence of second tumors. However, it failed to achieve cure in 15% of patients. We therefore believe that surgery remains the treatment of choice and that the decision to use imiquimod should be made on a case-by-case basis. A further consideration is that treatment with imiquimod could bring additional benefit to patients with multiple BCCs.</p><p id="par0170" class="elsevierStylePara elsevierViewall">Our study has some limitations. For instance, due to its retrospective design, we were unable to determine whether histologic subtype influenced the decision to choose surgery or imiquimod. As can be seen in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, the imiquimod and surgery groups differed in several respects, the most noteworthy of which was the higher frequency of superficial BCCs in patients treated with imiquimod, which would be consistent with the indications listed in the current SPC. The proportion of patients with a history of multiple BCCs and current multiple BCCs was higher in the group of patients who received imiquimod, meaning that they had a higher initial risk of developing subsequent BCCs, an interesting observation given that the rate of second BCCs was lower in this group.</p><p id="par0175" class="elsevierStylePara elsevierViewall">We were unable to investigate the significance of some of our findings owing to the small number of patients treated with imiquimod. The study of a larger series, ideally within the setting of a prospective, randomized trial, is needed to provide more reliable scientific evidence for these findings.</p><p id="par0180" class="elsevierStylePara elsevierViewall">In conclusion, imiquimod may reduce the risk of second BCCs and exert an effect for up to 2 years in local, regional, and lymphatic cancerization fields. Based on our findings, we believe that the concept of cancerization field should not be restricted to the local area but extended to include both the lymphatic and regional areas.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Ethical Disclosures</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Protection of humans and animals.</span><p id="par0185" class="elsevierStylePara elsevierViewall">The authors declare that no tests were carried out in humans or animals for the purpose of this study.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Confidentiality of data</span><p id="par0190" class="elsevierStylePara elsevierViewall">The authors declare that they have followed their hospital's protocol on the publication of data concerning patients and that all patients included in the study have received sufficient information and have given their written informed consent to participate in the study.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Right to privacy and informed consent</span><p id="par0195" class="elsevierStylePara elsevierViewall">The authors declare that no private patient data appear in this article.</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflicts of Interest</span><p id="par0200" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:2 [ "identificador" => "xres304925" "titulo" => array:6 [ 0 => "Abstract" 1 => "Background" 2 => "Objective" 3 => "Methods" 4 => "Results" 5 => "Conclusions" ] ] 1 => array:2 [ "identificador" => "xpalclavsec288082" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres304926" "titulo" => array:6 [ 0 => "Resumen" 1 => "Antecedentes" 2 => "Objetivo" 3 => "Métodos" 4 => "Resultados" 5 => "Conclusiones" ] ] 3 => array:2 [ "identificador" => "xpalclavsec288081" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Material and Methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:3 [ "identificador" => "sec0025" "titulo" => "Ethical Disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Protection of humans and animals." ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0040" "titulo" => "Right to privacy and informed consent" ] ] ] 9 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflicts of Interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-03-11" "fechaAceptado" => "2013-09-04" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec288082" "palabras" => array:6 [ 0 => "Basal cell carcinoma" 1 => "Imiquimod" 2 => "Cancerization field" 3 => "Risk" 4 => "Cutaneous neoplasm" 5 => "Second primary." ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec288081" "palabras" => array:6 [ 0 => "Carcinoma basocelular" 1 => "Imiquimod" 2 => "Campo de cancerización" 3 => "Riesgo" 4 => "Neoplasia cutánea" 5 => "Segundo primario." ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Patients with basal cell carcinoma (BCC) have an increased risk of subsequent BCCs. It is possible that imiquimod might reduce this risk by acting on the cancerization field.</p> <span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To examine the ability of imiquimod to reduce subsequent BCCs.</p> <span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Retrospective cohort study of patients with BCC treated at our hospital between 2003 and 2011. The patients were divided into 2 groups depending on whether they had been treated with surgery or with imiquimod. Comparing the 2 groups, we analyzed the development of new BCCs, the time that elapsed between first and subsequent tumors, and the site of occurrence of the second BCC with respect to the first one (local, same lymphatic drainage basin or anatomic region, or other). Survival methods were used to analyze the data.</p> <span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">We reviewed the charts of 623 patients. Of these, 550 had been treated with surgery (88.3%) and 71 with imiquimod (11.4%). Overall, a second BCC occurred in 36.4% of patients (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>227). The rate of occurrence was 38.2% in the surgery group and 23.9% in the imiquimod group (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.02). The hazard ratio for the occurrence of a subsequent BCC was 2.13 (95% <span class="elsevierStyleSmallCaps">CI</span>, 1.28-3.53) for patients treated with surgery compared with those treated with imiquimod. Imiquimod reduced the risk of a second BCC locally, regionally, and in the lymphatic drainage area. Our findings are limited by the retrospective nature of our study and the small number of patients treated with imiquimod.</p> <span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Imiquimod may reduce the risk of subsequent BCC in patients treated for BCC and its effect could last for up to 2 years in local, regional and lymphatic cancerization fields. We believe that the cancerization field concept should be expanded to include not only the local area, but also the pertinent anatomic region and the regional lymphatic drainage area.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0040">Antecedentes</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Los pacientes con carcinoma basocelular (CB) tienen riesgo de CB subsiguientes. El imiquimod podría reducir dicho riesgo mediante su efecto sobre el campo de cancerización.</p> <span class="elsevierStyleSectionTitle" id="sect0045">Objetivo</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Examinar la capacidad de imiquimod para reducir CB subsiguientes.</p> <span class="elsevierStyleSectionTitle" id="sect0050">Métodos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Estudio de cohorte retrospectivo de los pacientes con CB tratados en nuestro centro entre 2003 y 2011. Se establecieron 2 grupos según hubieran sido tratados con cirugía o imiquimod. Se comparó entre ambos la aparición de nuevos CB, analizando la proximidad del segundo CB respecto al primero (local, mismo territorio linfático, misma región anatómica, otro territorio) y el tiempo transcurrido entre el primer y segundo tumor. Para el análisis de los datos se emplearon estudios de supervivencia.</p> <span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Se revisaron 623 pacientes: 550 tratados con cirugía (88,3%), 2 con crioterapia y 71 con imiquimod (11,4%). Doscientos veintisiete pacientes (36,4%) presentaron un segundo CB (38,2% en el grupo cirugía, 23,9% en el grupo imiquimod, p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,02). La función de riesgo (hazard ratio) de sufrir un segundo CB cuando fueron tratados con cirugía comparado con imiquimod fue 2,13 (1,28-3,53). El imiquimod mostró menor riesgo de segundo CB a nivel local, regional y en el territorio linfático. Limitaciones: la naturaleza retrospectiva del estudio y el número de pacientes tratados con imiquimod fue limitado.</p> <span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">El tratamiento del CB con imiquimod podría reducir el riesgo de segundos CB. Este efecto podría permanecer hasta 2 años y se presentaría en los campos de cancerización local, regional y linfático. Creemos que el concepto de campo de cancerización debería extenderse no solo a nivel local, sino también regional y linfático.</p>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as: Graells J, Ojeda R, García-Cruz A. Efecto del imiquimod comparado con la cirugía sobre el campo de cancerización en el carcinoma basocelular. Actas Dermosifiliogr. 2014;105:53–59.</p>" ] ] "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" => 1831 "Ancho" => 1666 "Tamanyo" => 94563 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Survival curve (Kaplan-Meier) showing the development of a second basal cell carcinoma (BCC) in patients with an initial BCC treated with surgery or imiquimod.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 3331 "Ancho" => 3000 "Tamanyo" => 325964 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Survival curves (Kaplan-Meier) showing the development of a second basal cell carcinoma (BCC) in different cancerization fields in patients with an initial BCC treated with surgery or imiquimod. A, Local; B, Lymphatic; C, Regional; D, Outside the cancerization field.</p>" ] ] 2 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "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 " 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">Treatment</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="" 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">Imiquimod \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">Surgery \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">Patients, 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="" 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">71 \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">550 \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">Mean age, y \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67.61 \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">67.95 \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">Sex \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">Male \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">35 (49.30) \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">312 (56.73) \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="" 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">Female \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 (50.70) \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">238 (43.27) \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">Mean previous BCCs, 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="" 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.95 \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">0.37 \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">Initial multiple BCCs (≥<span class="elsevierStyleHsp" style=""></span>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="" 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (11.27) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 (3.64) \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">Location \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">Head and neck \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">51 (72.86) \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">432 (78.55) \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="" 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">Trunk \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">14 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">87 (15.82) \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="" 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">Limbs \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 (7.14) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">31 (5.64) \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">Histologic subtype \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">Superficial \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">34 (47.89) \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">95 (17.27) \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="" 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">Infiltrating \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">22 (30.99) \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">278 (50.55) \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="" 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">Nodular \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 (1.41) \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">170 (30.91) \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="" 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">Not specified \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">14 (19.72) \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">7 (1.27) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab451002.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Data expressed as number (%) of patients unless otherwise specified.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Baseline Characteristics of Patients With Basal Cell Carcinoma (BCC) Treated With Surgery or Imiquimod.<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></p>" ] ] 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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Variable \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">Hazard Ratio \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">95% CI \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"><span class="elsevierStyleItalic">P</span> Value \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">Treatment (surgery vs imiquimod) \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">2.13 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.28-3.53 \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">.0032 \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">Age \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">1.02 \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">1.00-1.03 \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">.0003 \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">Male sex \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">1.34 \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">1.02-1.75 \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">.033 \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">Previous multiple BCCs (≥<span class="elsevierStyleHsp" style=""></span>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">2.13 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.32-3.44 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.002 \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">Initial multiple BCCs (≥<span class="elsevierStyleHsp" style=""></span>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">1.62 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.98-2.67 \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">.055 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab451001.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Multivariate Analysis of Risk of Second Basal Cell Carcinoma (BCC).</p>" ] ] 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="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">No. of Events</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">Hazard Ratio \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">95% CI \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"><span class="elsevierStyleItalic">P</span> Value \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">Imiquimod (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>71) \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">Surgery (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>550) \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><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="" 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">Local \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">73 \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">2.12 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.91-4.97 \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">.08 \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">Lymphatic \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">8 \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">101 \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">2.23 \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">1.07-4.65 \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">.03 \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">Regional \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">11 \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">160 \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">2.47 \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">1.33-4.59 \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">.004 \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">Outside the cancerization field \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="char" 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">1.59 \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">0.66-3.83 \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></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab451000.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Risk of Second Basal Cell Carcinoma Comparing Surgery and Imiquimod in Local, Lymphatic, and Regional Cancerization Fields and Outside Cancerization Field.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:25 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Incidence estimate of nonmelanoma skin cancer in the United States, 2006" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H.W. Rogers" 1 => "M.A. Weinstock" 2 => "A.R. Harris" 3 => "M.R. Hinckley" 4 => "S.R. Feldman" 5 => "A.B. Fleischer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/archdermatol.2010.19" "Revista" => array:6 [ "tituloSerie" => "Arch Dermatol" "fecha" => "2010" "volumen" => "146" "paginaInicial" => "283" "paginaFinal" => "287" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20231499" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cumulative risks and rates of subsequent basal cell carcinomas in the Netherlands" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S.C. Flohil" 1 => "S. Koljenovic" 2 => "E.R.M. de Haas" 3 => "L.I.H. Overbeek" 4 => "E. de Vries" 5 => "T. Nijsten" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2133.2011.10488.x" "Revista" => array:6 [ "tituloSerie" => "Br J Dermatol" "fecha" => "2011" "volumen" => "165" "paginaInicial" => "874" "paginaFinal" => "881" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21711333" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The risk and risk factors of a second nonmelanoma skin cancer: a study in a Mediterranean population" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J. Graells" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Eur Acad Dermatol Venereol" "fecha" => "2004" "volumen" => "18" "paginaInicial" => "142" "paginaFinal" => "147" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15009290" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Risk of subsequent basal cell carcinoma and squamous cell carcinoma of the skin among patients with prior skin cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M.R. Karagas" 1 => "T.A. Stukel" 2 => "E.R. Greenberg" 3 => "J.A. Baron" 4 => "L.A. Mott" 5 => "R.S. Stern" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "JAMA" "fecha" => "1992" "volumen" => "267" "paginaInicial" => "3305" "paginaFinal" => "3310" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1597912" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Predictors of basal cell carcinoma in high-risk patients in the VATTC (VA topical tretinoin chemoprevention) trial" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "VATTC Trial Group" "etal" => false "autores" => array:5 [ 0 => "R.K. Dyer" 1 => "M.A. Weinstock" 2 => "T.S. Cohen" 3 => "A.E. Rizzo" 4 => "S.F. Bingham" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/jid.2012.227" "Revista" => array:6 [ "tituloSerie" => "J Invest Dermatol" "fecha" => "2012" "volumen" => "132" "paginaInicial" => "2544" "paginaFinal" => "2551" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22810303" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "«Field cancerization» in oral stratified squamous epithelium. Clinical implications of multicentric origin" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "D.P. Slaughter" 1 => "H.W. Southwick" 2 => "W. Smejkal" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Cancer" "fecha" => "1953" "volumen" => "6" "paginaInicial" => "963" "paginaFinal" => "968" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/13094644" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Low incidence of new actinic keratoses after topical 5% imiquimod cream treatment: A long-term follow-up study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "E. Stockfleth" 1 => "E. Christophers" 2 => "B. Benninghoff" 3 => "W. Sterry" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/archderm.140.12.1542-a" "Revista" => array:5 [ "tituloSerie" => "Arch Dermatol" "fecha" => "2004" "volumen" => "140" "paginaInicial" => "1542" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15611446" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Actinic keratosis and field cancerisation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "E. Stockfleth" 1 => "J.P. Ortonne" 2 => "A. Alomar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1684/ejd.2011.1305" "Revista" => array:7 [ "tituloSerie" => "Eur J Dermatol" "fecha" => "2011" "volumen" => "21" "numero" => "Suppl 1" "paginaInicial" => "3" "paginaFinal" => "12" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21628133" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Topical imiquimod or fluorouracil therapy for basal and squamous cell carcinoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "W.E. Love" 1 => "J.D. Bernhard" 2 => "J.S. Bordeaux" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/archdermatol.2009.291" "Revista" => array:6 [ "tituloSerie" => "Arch Dermatol" "fecha" => "2009" "volumen" => "145" "paginaInicial" => "1431" "paginaFinal" => "1438" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20026854" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Immune response modifiers-mode of action" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Schiller" 1 => "D. Metze" 2 => "T.A. Luger" 3 => "S. Grabbe" 4 => "M. Gunzer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.0906-6705.2006.00414.x" "Revista" => array:6 [ "tituloSerie" => "Exp Dermatol" "fecha" => "2006" "volumen" => "15" "paginaInicial" => "331" "paginaFinal" => "341" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16630072" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Open study of the efficacy and mechanism of action of topical imiquimod in basal cell carcinoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "D. Vidal" 1 => "X. Matias-Guiu" 2 => "A. Alomar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2230.2004.01601.x" "Revista" => array:6 [ "tituloSerie" => "Clin Exp Dermatol" "fecha" => "2004" "volumen" => "29" "paginaInicial" => "518" "paginaFinal" => "525" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15347339" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Imiquimod treatment associated with a reduction in new skin cancer formation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C. Czarnecki" 1 => "D. Czarnecki" 2 => "S. Carroll" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2230.2008.02925.x" "Revista" => array:5 [ "tituloSerie" => "Clin Exp Dermatol" "fecha" => "2008" "volumen" => "34" "paginaInicial" => "92" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19076806" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. Hemmi" 1 => "T. Kaisho" 2 => "O. Takeuchi" 3 => "S. Sato" 4 => "H. Sanjo" 5 => "K. Hoshino" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ni758" "Revista" => array:6 [ "tituloSerie" => "Nat Immunol" "fecha" => "2002" "volumen" => "3" "paginaInicial" => "196" "paginaFinal" => "200" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11812998" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The appearance of inflammatory papules in the skin surrounding areas treated with imiquimod cream for basal cell carcinoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "G. Stinco" 1 => "A. Frattasio" 2 => "M. Forcione" 3 => "E. Quinkenstein" 4 => "N. Finato" 5 => "P. Patrone" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2133.2007.08301.x" "Revista" => array:6 [ "tituloSerie" => "Br J Dermatol" "fecha" => "2008" "volumen" => "158" "paginaInicial" => "408" "paginaFinal" => "409" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18028501" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pharmacokinetics and safety of imiquimod 5% cream in the treatment of molluscum contagiosum in children" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "P.E. Myhre" 1 => "M.L. Levy" 2 => "L.F. Eichenfield" 3 => "V.B. Kolb" 4 => "S.L. Fielder" 5 => "T.C. Meng" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1525-1470.2007.00590.x" "Revista" => array:6 [ "tituloSerie" => "Pediatr Dermatol" "fecha" => "2008" "volumen" => "25" "paginaInicial" => "88" "paginaFinal" => "95" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18304162" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Development of subacute cutaneous lupus erythematosus associated with the use of imiquimod to treat actinic keratoses" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "T.J. Burnett" 1 => "J.C. 3rd English" 2 => "L.K. Ferris" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Drugs Dermatol" "fecha" => "2010" "volumen" => "9" "paginaInicial" => "1022" "paginaFinal" => "1024" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20684157" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Imiquimod 5% cream induced psoriasis: A case report, summary of the literature and mechanism" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "U. Patel" 1 => "N.M. Mark" 2 => "B.C. Machler" 3 => "V.J. Levine" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2133.2010.10124.x" "Revista" => array:6 [ "tituloSerie" => "Br J Dermatol" "fecha" => "2011" "volumen" => "164" "paginaInicial" => "670" "paginaFinal" => "672" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21062268" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ultraviolet B radiation suppresses endocytosis, subsequent maturation, and migration activity of Langerhans cell-like dendritic cells" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "K. Mizuno" 1 => "H. Okamoto" 2 => "T. Horio" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1046/j.0022-202X.2004.22206.x" "Revista" => array:6 [ "tituloSerie" => "J Invest Dermatol" "fecha" => "2004" "volumen" => "122" "paginaInicial" => "300" "paginaFinal" => "306" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15009709" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Imiquimod and lymphatic field clearance: A new hypothesis based on a remote immune action on skin cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M. Akkilic-Materna" 1 => "C. Massone" 2 => "P. Komericki" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2340/00015555-1099" "Revista" => array:6 [ "tituloSerie" => "Acta Derm Venereol" "fecha" => "2011" "volumen" => "91" "paginaInicial" => "432" "paginaFinal" => "435" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21547348" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A randomised study of topical 5% imiquimod vs topical 5-fluorouracil vs cryosurgery in immunocompetent patients with actinic keratoses: A comparison of clinical and histological outcomes including 1-year follow-up" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "N. Krawtchenko" 1 => "J. Roewert-Huber" 2 => "M. Ulrich" 3 => "I. Mann" 4 => "W. Sterry" 5 => "E. Stockfleth" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Br J Dermatol" "fecha" => "2007" "volumen" => "2" "numero" => "157 Suppl" "paginaInicial" => "34" "paginaFinal" => "40" ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vehicle-controlled, double-blind, randomized study of imiquimod 5% cream applied 3 days per week in one or two courses of treatment for actinic keratoses on the head" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Jorizzo" 1 => "S. Dinehart" 2 => "R. Matheson" 3 => "J.K. Moore" 4 => "M. Ling" 5 => "T.L. Fox" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaad.2007.01.047" "Revista" => array:6 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "2007" "volumen" => "57" "paginaInicial" => "265" "paginaFinal" => "268" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17512087" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effectiveness and satisfaction with imiquimod for the treatment of superficial basal cell carcinoma in daily dermatological practice" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "on behalf of the BASALE Study Group" "etal" => false "autores" => array:1 [ 0 => "E. Dauden" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1468-3083.2011.03977.x" "Revista" => array:6 [ "tituloSerie" => "J Eur Acad Dermatol Venereol" "fecha" => "2011" "volumen" => "25" "paginaInicial" => "1304" "paginaFinal" => "1310" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21348896" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "High discordance between punch biopsy and excision in establishing basal cell carcinoma subtype: analysis of 500 cases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "E.A. Wolberink" 1 => "M.C. Pasch" 2 => "M. Zeiler" 3 => "P.E. van Erp" 4 => "J.M. Gerritsen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1468-3083.2012.04628.x" "Revista" => array:6 [ "tituloSerie" => "J Eur Acad Dermatol Venereol" "fecha" => "2013" "volumen" => "27" "paginaInicial" => "985" "paginaFinal" => "989" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22759209" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Need for a new skin cancer management strategy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S. Van der Geer" 1 => "H.A. Reijers" 2 => "H.F.J.M. van Tuijl" 3 => "H. de Vries" 4 => "G.A. Krekels" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/archdermatol.2010.1" "Revista" => array:6 [ "tituloSerie" => "Arch Dermatol" "fecha" => "2010" "volumen" => "146" "paginaInicial" => "332" "paginaFinal" => "336" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20231509" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Patients who have multiple skin cancers develop new skin cancers at a constant rate" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C. Czarnecki" 1 => "D. Czarnecki" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Arch Dermatol" "fecha" => "2002" "volumen" => "138" "paginaInicial" => "125" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11790182" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/15782190/0000010500000001/v1_201401220123/S1578219013002692/v1_201401220123/en/main.assets" "Apartado" => array:4 [ "identificador" => "6155" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original Articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15782190/0000010500000001/v1_201401220123/S1578219013002692/v1_201401220123/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219013002692?idApp=UINPBA000044" ]
| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 19 | 9 | 28 |
| 2024 Octubre | 91 | 42 | 133 |
| 2024 Septiembre | 101 | 31 | 132 |
| 2024 Agosto | 103 | 76 | 179 |
| 2024 Julio | 80 | 36 | 116 |
| 2024 Junio | 66 | 33 | 99 |
| 2024 Mayo | 67 | 25 | 92 |
| 2024 Abril | 50 | 24 | 74 |
| 2024 Marzo | 52 | 27 | 79 |
| 2024 Febrero | 53 | 27 | 80 |
| 2024 Enero | 46 | 37 | 83 |
| 2023 Diciembre | 41 | 13 | 54 |
| 2023 Noviembre | 63 | 22 | 85 |
| 2023 Octubre | 49 | 22 | 71 |
| 2023 Septiembre | 55 | 35 | 90 |
| 2023 Agosto | 39 | 13 | 52 |
| 2023 Julio | 32 | 36 | 68 |
| 2023 Junio | 43 | 20 | 63 |
| 2023 Mayo | 40 | 24 | 64 |
| 2023 Abril | 33 | 16 | 49 |
| 2023 Marzo | 27 | 20 | 47 |
| 2023 Febrero | 39 | 28 | 67 |
| 2023 Enero | 46 | 24 | 70 |
| 2022 Diciembre | 46 | 39 | 85 |
| 2022 Noviembre | 16 | 29 | 45 |
| 2022 Octubre | 29 | 17 | 46 |
| 2022 Septiembre | 21 | 40 | 61 |
| 2022 Agosto | 23 | 39 | 62 |
| 2022 Julio | 27 | 33 | 60 |
| 2022 Junio | 18 | 25 | 43 |
| 2022 Mayo | 33 | 33 | 66 |
| 2022 Abril | 33 | 41 | 74 |
| 2022 Marzo | 37 | 57 | 94 |
| 2022 Febrero | 18 | 27 | 45 |
| 2022 Enero | 25 | 35 | 60 |
| 2021 Diciembre | 26 | 29 | 55 |
| 2021 Noviembre | 30 | 48 | 78 |
| 2021 Octubre | 35 | 49 | 84 |
| 2021 Septiembre | 33 | 38 | 71 |
| 2021 Agosto | 20 | 33 | 53 |
| 2021 Julio | 31 | 34 | 65 |
| 2021 Junio | 33 | 37 | 70 |
| 2021 Mayo | 38 | 27 | 65 |
| 2021 Abril | 58 | 31 | 89 |
| 2021 Marzo | 69 | 17 | 86 |
| 2021 Febrero | 56 | 24 | 80 |
| 2021 Enero | 29 | 23 | 52 |
| 2020 Diciembre | 23 | 14 | 37 |
| 2020 Noviembre | 14 | 13 | 27 |
| 2020 Octubre | 17 | 9 | 26 |
| 2020 Septiembre | 28 | 18 | 46 |
| 2020 Agosto | 31 | 18 | 49 |
| 2020 Julio | 36 | 13 | 49 |
| 2020 Junio | 32 | 19 | 51 |
| 2020 Mayo | 24 | 32 | 56 |
| 2020 Abril | 26 | 14 | 40 |
| 2020 Marzo | 25 | 13 | 38 |
| 2020 Febrero | 3 | 1 | 4 |
| 2020 Enero | 4 | 0 | 4 |
| 2019 Diciembre | 8 | 3 | 11 |
| 2019 Noviembre | 4 | 0 | 4 |
| 2019 Octubre | 1 | 0 | 1 |
| 2019 Septiembre | 9 | 0 | 9 |
| 2019 Agosto | 6 | 0 | 6 |
| 2019 Julio | 4 | 1 | 5 |
| 2019 Junio | 4 | 2 | 6 |
| 2019 Mayo | 6 | 29 | 35 |
| 2019 Abril | 2 | 1 | 3 |
| 2019 Marzo | 2 | 5 | 7 |
| 2019 Febrero | 3 | 0 | 3 |
| 2018 Diciembre | 4 | 0 | 4 |
| 2018 Noviembre | 2 | 0 | 2 |
| 2018 Octubre | 7 | 0 | 7 |
| 2018 Septiembre | 3 | 0 | 3 |
| 2018 Marzo | 6 | 1 | 7 |
| 2018 Febrero | 24 | 6 | 30 |
| 2018 Enero | 34 | 5 | 39 |
| 2017 Diciembre | 40 | 9 | 49 |
| 2017 Noviembre | 33 | 2 | 35 |
| 2017 Octubre | 40 | 4 | 44 |
| 2017 Septiembre | 32 | 4 | 36 |
| 2017 Agosto | 28 | 5 | 33 |
| 2017 Julio | 24 | 6 | 30 |
| 2017 Junio | 38 | 9 | 47 |
| 2017 Mayo | 20 | 10 | 30 |
| 2017 Abril | 24 | 5 | 29 |
| 2017 Marzo | 18 | 2 | 20 |
| 2017 Febrero | 19 | 6 | 25 |
| 2017 Enero | 29 | 7 | 36 |
| 2016 Diciembre | 40 | 8 | 48 |
| 2016 Noviembre | 53 | 9 | 62 |
| 2016 Octubre | 39 | 10 | 49 |
| 2016 Septiembre | 63 | 12 | 75 |
| 2016 Agosto | 58 | 4 | 62 |
| 2016 Julio | 42 | 5 | 47 |
| 2016 Junio | 9 | 0 | 9 |
| 2016 Mayo | 16 | 9 | 25 |
| 2016 Abril | 12 | 1 | 13 |
| 2016 Marzo | 9 | 0 | 9 |
| 2016 Febrero | 6 | 6 | 12 |
| 2016 Enero | 8 | 1 | 9 |
| 2015 Diciembre | 7 | 1 | 8 |
| 2015 Noviembre | 10 | 1 | 11 |
| 2015 Octubre | 5 | 0 | 5 |
| 2015 Septiembre | 5 | 4 | 9 |
| 2015 Agosto | 6 | 2 | 8 |
| 2015 Julio | 28 | 3 | 31 |
| 2015 Junio | 28 | 3 | 31 |
| 2015 Mayo | 40 | 8 | 48 |
| 2015 Abril | 20 | 3 | 23 |
| 2015 Marzo | 34 | 5 | 39 |
| 2015 Febrero | 13 | 5 | 18 |
| 2015 Enero | 15 | 2 | 17 |
| 2014 Diciembre | 22 | 2 | 24 |
| 2014 Noviembre | 15 | 5 | 20 |
| 2014 Octubre | 22 | 7 | 29 |
| 2014 Septiembre | 14 | 5 | 19 |
| 2014 Agosto | 13 | 2 | 15 |
| 2014 Julio | 14 | 6 | 20 |
| 2014 Junio | 23 | 4 | 27 |
| 2014 Mayo | 24 | 7 | 31 |
| 2014 Abril | 23 | 9 | 32 |
| 2014 Marzo | 16 | 7 | 23 |
| 2014 Febrero | 10 | 8 | 18 |
| 2014 Enero | 0 | 1 | 1 |
Mostrar todo
