Estadísticas

 array:24 [
  "pii" => "S0001731018304976"
  "issn" => "00017310"
  "doi" => "10.1016/j.ad.2018.10.006"
  "estado" => "S300"
  "fechaPublicacion" => "2019-07-01"
  "aid" => "2100"
  "copyright" => "AEDV"
  "copyrightAnyo" => "2018"
  "documento" => "article"
  "crossmark" => 1
  "subdocumento" => "rev"
  "cita" => "Actas Dermosifiliogr. 2019;110:426-33"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:2 [
    "total" => 664
    "formatos" => array:2 [
      "HTML" => 473
      "PDF" => 191
    ]
  ]
  "Traduccion" => array:1 [
    "en" => array:19 [
      "pii" => "S1578219019301684"
      "issn" => "15782190"
      "doi" => "10.1016/j.adengl.2019.05.007"
      "estado" => "S300"
      "fechaPublicacion" => "2019-07-01"
      "aid" => "2100"
      "copyright" => "Elsevier España, S.L.U. and AEDV"
      "documento" => "article"
      "crossmark" => 1
      "subdocumento" => "rev"
      "cita" => "Actas Dermosifiliogr. 2019;110:426-33"
      "abierto" => array:3 [
        "ES" => true
        "ES2" => true
        "LATM" => true
      ]
      "gratuito" => true
      "lecturas" => array:2 [
        "total" => 3
        "formatos" => array:2 [
          "HTML" => 1
          "PDF" => 2
        ]
      ]
      "en" => array:13 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Review</span>"
        "titulo" => "Perineural Invasion in Cutaneous Squamous Cell Carcinoma"
        "tienePdf" => "en"
        "tieneTextoCompleto" => "en"
        "tieneResumen" => array:2 [
          0 => "en"
          1 => "es"
        ]
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "426"
            "paginaFinal" => "433"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "es" => array:1 [
            "titulo" => "Invasi&#243;n perineural en el carcinoma epidermoide cut&#225;neo"
          ]
        ]
        "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" => 620
                "Ancho" => 900
                "Tamanyo" => 66481
              ]
            ]
            "descripcion" => array:1 [
              "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Clinical perineural infiltration&#58; supraorbital nerve thickening&#46;</p>"
            ]
          ]
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "M&#46;P&#46; P&#233;rez Garc&#237;a, A&#46; Mateu Puchades, O&#46; Sanmart&#237;n Jim&#233;nez"
            "autores" => array:3 [
              0 => array:2 [
                "nombre" => "M&#46;P&#46;"
                "apellidos" => "P&#233;rez Garc&#237;a"
              ]
              1 => array:2 [
                "nombre" => "A&#46;"
                "apellidos" => "Mateu Puchades"
              ]
              2 => array:2 [
                "nombre" => "O&#46;"
                "apellidos" => "Sanmart&#237;n Jim&#233;nez"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "en"
      "Traduccion" => array:1 [
        "es" => array:9 [
          "pii" => "S0001731018304976"
          "doi" => "10.1016/j.ad.2018.10.006"
          "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/S0001731018304976?idApp=UINPBA000044"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219019301684?idApp=UINPBA000044"
      "url" => "/15782190/0000011000000006/v1_201907040838/S1578219019301684/v1_201907040838/en/main.assets"
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S0001731019301231"
    "issn" => "00017310"
    "doi" => "10.1016/j.ad.2018.11.009"
    "estado" => "S300"
    "fechaPublicacion" => "2019-07-01"
    "aid" => "2189"
    "copyright" => "AEDV"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "rev"
    "cita" => "Actas Dermosifiliogr. 2019;110:434-47"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 640
      "formatos" => array:2 [
        "HTML" => 454
        "PDF" => 186
      ]
    ]
    "es" => array:14 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">REVISI&#211;N</span>"
      "titulo" => "Melanoma cut&#225;neo en el anciano&#58; revisi&#243;n de un problema creciente"
      "tienePdf" => "es"
      "tieneTextoCompleto" => "es"
      "tieneResumen" => array:3 [
        0 => "es"
        1 => "es"
        2 => "en"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "434"
          "paginaFinal" => "447"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "en" => array:1 [
          "titulo" => "Cutaneous Melanoma in the Elderly&#58; Review of a Growing Problem"
        ]
      ]
      "contieneResumen" => array:2 [
        "es" => true
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "es" => true
      ]
      "contienePdf" => array:1 [
        "es" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 1
        "multimedia" => array:5 [
          "identificador" => "fig0045"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => false
          "mostrarDisplay" => true
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "fx1.jpeg"
              "Alto" => 718
              "Ancho" => 1333
              "Tamanyo" => 137371
            ]
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "N&#46; Iglesias-Pena, S&#46; Paradela, A&#46; Tejera-Vaquerizo, A&#46; Boada, E&#46; Fonseca"
          "autores" => array:5 [
            0 => array:2 [
              "nombre" => "N&#46;"
              "apellidos" => "Iglesias-Pena"
            ]
            1 => array:2 [
              "nombre" => "S&#46;"
              "apellidos" => "Paradela"
            ]
            2 => array:2 [
              "nombre" => "A&#46;"
              "apellidos" => "Tejera-Vaquerizo"
            ]
            3 => array:2 [
              "nombre" => "A&#46;"
              "apellidos" => "Boada"
            ]
            4 => array:2 [
              "nombre" => "E&#46;"
              "apellidos" => "Fonseca"
            ]
          ]
        ]
      ]
      "resumen" => array:1 [
        0 => array:3 [
          "titulo" => "Graphical abstract"
          "clase" => "graphical"
          "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><elsevierMultimedia ident="fig0045"></elsevierMultimedia></p></span>"
        ]
      ]
    ]
    "idiomaDefecto" => "es"
    "Traduccion" => array:1 [
      "en" => array:9 [
        "pii" => "S1578219019301817"
        "doi" => "10.1016/j.adengl.2019.05.012"
        "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/S1578219019301817?idApp=UINPBA000044"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731019301231?idApp=UINPBA000044"
    "url" => "/00017310/0000011000000006/v1_201907020633/S0001731019301231/v1_201907020633/es/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S0001731019301115"
    "issn" => "00017310"
    "doi" => "10.1016/j.ad.2019.02.007"
    "estado" => "S300"
    "fechaPublicacion" => "2019-07-01"
    "aid" => "2177"
    "copyright" => "AEDV"
    "documento" => "simple-article"
    "crossmark" => 1
    "subdocumento" => "cor"
    "cita" => "Actas Dermosifiliogr. 2019;110:425"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 379
      "formatos" => array:3 [
        "EPUB" => 1
        "HTML" => 263
        "PDF" => 115
      ]
    ]
    "es" => array:10 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Comentarios Editoriales</span>"
      "titulo" => "Biopsia selectiva del ganglio centinela"
      "tienePdf" => "es"
      "tieneTextoCompleto" => "es"
      "paginas" => array:1 [
        0 => array:1 [
          "paginaInicial" => "425"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "en" => array:1 [
          "titulo" => "Sentinel Lymph Node Biopsy"
        ]
      ]
      "contieneTextoCompleto" => array:1 [
        "es" => true
      ]
      "contienePdf" => array:1 [
        "es" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "S&#46; Mart&#237;nez Garc&#237;a"
          "autores" => array:1 [
            0 => array:2 [
              "nombre" => "S&#46;"
              "apellidos" => "Mart&#237;nez Garc&#237;a"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "es"
    "Traduccion" => array:1 [
      "en" => array:9 [
        "pii" => "S1578219019301647"
        "doi" => "10.1016/j.adengl.2019.02.021"
        "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/S1578219019301647?idApp=UINPBA000044"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731019301115?idApp=UINPBA000044"
    "url" => "/00017310/0000011000000006/v1_201907020633/S0001731019301115/v1_201907020633/es/main.assets"
  ]
  "es" => array:19 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">REVISI&#211;N</span>"
    "titulo" => "Invasi&#243;n perineural en el carcinoma epidermoide cut&#225;neo"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "426"
        "paginaFinal" => "433"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "M&#46;P&#46; P&#233;rez Garc&#237;a, A&#46; Mateu Puchades, O&#46; Sanmart&#237;n Jim&#233;nez"
        "autores" => array:3 [
          0 => array:4 [
            "nombre" => "M&#46;P&#46;"
            "apellidos" => "P&#233;rez Garc&#237;a"
            "email" => array:1 [
              0 => "glupipg@hotmail.com"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "A&#46;"
            "apellidos" => "Mateu Puchades"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "O&#46;"
            "apellidos" => "Sanmart&#237;n Jim&#233;nez"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:3 [
          0 => array:3 [
            "entidad" => "Servicio de Dermatolog&#237;a&#44; Hospital Marina Salud&#44; Denia&#44; Alicante&#44; Espa&#241;a"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Servicio de Dermatolog&#237;a&#44; Hospital Dr&#46; Peset&#44; Valencia&#44; Espa&#241;a"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Servicio de Dermatolog&#237;a&#44; Instituto Valenciano de Oncolog&#237;a&#44; Valencia&#44; Espa&#241;a"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Autor para correspondencia&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "en" => array:1 [
        "titulo" => "Perineural Invasion in Cutaneous Squamous Cell Carcinoma"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 1
      "multimedia" => array:5 [
        "identificador" => "fig0035"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "fx1.jpeg"
            "Alto" => 985
            "Ancho" => 1333
            "Tamanyo" => 210478
          ]
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Introducci&#243;n</span><p id="par0005" class="elsevierStylePara elsevierViewall">La infiltraci&#243;n perineural &#40;IPN&#41; fue descrita por primera vez por Cruveilhier<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">2</span></a> en 1835&#44; en un caso de afectaci&#243;n del nervio facial por un carcinoma mamario&#46; Se define como la infiltraci&#243;n de c&#233;lulas tumorales a trav&#233;s de los nervios&#44; que se extienden por el espacio perineural<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">1</span></a> mostrando poca tendencia a invadir el nervio en profundidad&#46; Por tanto&#44; la IPN no es una variedad de diseminaci&#243;n linf&#225;tica ni hem&#225;tica&#44; sino que representa una extensi&#243;n directa del tumor primario<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">3&#44;4</span></a>&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Epidemiolog&#237;a</span><p id="par0010" class="elsevierStylePara elsevierViewall">La IPN en los tumores cut&#225;neos est&#225; infravalorada&#44; y con frecuencia pasa desapercibida tanto cl&#237;nica como radiogr&#225;ficamente&#46; La incidencia en carcinoma epidermoide cut&#225;neo &#40;CEC&#41; es del 2&#44;4 al 14&#37;<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">5&#8211;7</span></a>&#44; asciende al 24&#37; en los CEC recurrentes<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">8</span></a>&#44; y si nos referimos exclusivamente a los CEC de mucosas de cabeza y cuello<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">9</span></a>&#44; es del 29&#37;&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Tambi&#233;n var&#237;a seg&#250;n el tama&#241;o tumoral&#44; estando presente en el 64&#37; de los tumores mayores de 2&#44;5<span class="elsevierStyleHsp" style=""></span>cm y en el 11&#37; de los tumores menores de 2&#44;5<span class="elsevierStyleHsp" style=""></span>cm<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">10</span></a>&#44; y el subtipo histol&#243;gico&#44; siendo m&#225;s frecuente en los CEC pobremente diferenciados<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">9</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">La edad media<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">11</span></a> de los pacientes se sit&#250;a en los 64 a&#241;os&#44; con un claro predominio por el sexo masculino &#40;77&#37;&#41;&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Patog&#233;nesis</span><p id="par0025" class="elsevierStylePara elsevierViewall">Inicialmente&#44; se cre&#237;a que consist&#237;a en una propagaci&#243;n linf&#225;tica del tumor a los nervios&#46; Posteriormente se consider&#243; a la vaina del nervio como una v&#237;a de baja resistencia para la diseminaci&#243;n del tumor<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">10</span></a>&#44; teor&#237;a que ha quedado refutada al demostrar con microscop&#237;a electr&#243;nica la elevada selectividad de la barrera hematoneural<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">4&#44;12&#44;13</span></a>&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">En la actualidad se considera que la IPN se produce por invasi&#243;n&#44; como resultado de la interacci&#243;n rec&#237;proca y din&#225;mica entre el tumor y las terminaciones nerviosas<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">4&#44;14</span></a>&#46; Se han identificado varios agentes neurotr&#243;picos implicados&#58; el factor de crecimiento neural<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">15</span></a>&#44; la mol&#233;cula de adhesi&#243;n neural celular<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">16&#44;17</span></a>&#44; el factor neurotr&#243;fico derivado del cerebro&#44; la neurotrofina 3<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">4</span></a>&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">En un estudio reciente&#44; Binmadi et al&#46; muestran que plexin-B1 &#40;un subtipo de prote&#237;nas que interviene en la adhesi&#243;n de las c&#233;lulas nerviosas y la migraci&#243;n de los axones durante el desarrollo<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">18</span></a>&#41; se sobreexpresa en tejidos y l&#237;neas celulares de neoplasias neurotr&#243;picas y promueve que los nervios expresen su ligando&#44; semaforina 4<span class="elsevierStyleHsp" style=""></span>D&#44; a trav&#233;s de la v&#237;a Rho&#47;Rho quinasa-dependiente<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">19</span></a>&#46; Los tumores atraen a los nervios a trav&#233;s de este mismo sistema de prote&#237;nas&#44; lo que sugiere que tanto la plexina B1 como la semaforina 4<span class="elsevierStyleHsp" style=""></span>D son importantes en la promoci&#243;n de la PNI&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Diagn&#243;stico</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Clasificaci&#243;n de la infiltraci&#243;n perineural</span><p id="par0040" class="elsevierStylePara elsevierViewall">En el 60-70&#37; de los pacientes con CEC e IPN esta se presenta como un hallazgo incidental&#44; es decir&#44; se identifica en el estudio histol&#243;gico del tumor tras la cirug&#237;a&#44; sin sintomatolog&#237;a ni evidencia radiol&#243;gica&#44; denomin&#225;ndose IPN incidental o microsc&#243;pica<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">20&#44;21</span></a>&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Cuando aparecen s&#237;ntomas como dolor&#44; parestesias&#44; disestesias&#44; anestesia o par&#225;lisis y&#47;o evidencia radiol&#243;gica de la extensi&#243;n de la IPN&#44; se clasifica como IPN cl&#237;nica<a class="elsevierStyleCrossRefs" href="#bib0545"><span class="elsevierStyleSup">22&#44;23</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; Los primeros s&#237;ntomas suelen ser muy sutiles&#44; sensaci&#243;n de hormigueo o entumecimiento&#44; pudiendo pasar desapercibidos salvo que se tenga un alto &#237;ndice de sospecha de IPN<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">24</span></a>&#46; El hecho de que en ocasiones en las pruebas de imagen de pacientes con IPN cl&#237;nica no se observan alteraciones&#44; a&#250;n dificulta m&#225;s su manejo<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">25&#44;26</span></a>&#46; En casos m&#225;s avanzados puede aparecer dolor o d&#233;ficit motor &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">De esta forma puede diagnosticarse err&#243;neamente de par&#225;lisis de Bell&#44; neuralgia del trig&#233;mino o accidente cerebrovascular&#44; demorando el diagn&#243;stico y con ello empeorando el pron&#243;stico de estos pacientes<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">27</span></a>&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Anatom&#237;a de los nervios de la regi&#243;n facial</span><p id="par0055" class="elsevierStylePara elsevierViewall">El nervio facial y el trig&#233;mino son los nervios que con mayor frecuencia se ven afectados&#44; especialmente la rama maxilar<a class="elsevierStyleCrossRefs" href="#bib0455"><span class="elsevierStyleSup">28&#44;29</span></a>&#44; habi&#233;ndose descrito casos aislados de CEC fuera de cabeza y cuello con IPN cl&#237;nica<a class="elsevierStyleCrossRefs" href="#bib0465"><span class="elsevierStyleSup">30&#44;31</span></a>&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Es fundamental conocer su distribuci&#243;n anat&#243;mica para entender la IPN&#44; as&#237; como su abordaje terap&#233;utico<a class="elsevierStyleCrossRefs" href="#bib0475"><span class="elsevierStyleSup">32&#8211;34</span></a>&#46;</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Nervio trig&#233;mino</span><p id="par0065" class="elsevierStylePara elsevierViewall">Es el nervio craneal m&#225;s vulnerable para la IPN de c&#225;ncer cut&#225;neo&#44; debido a la rica inervaci&#243;n cut&#225;nea en la mayor&#237;a de las regiones expuestas a los rayos UV de la cabeza y el cuello&#46; Emerge de la protuberancia&#44; con una ra&#237;z sensitiva y una ra&#237;z motora&#46; Su ganglio sensitivo &#40;semilunar&#41; asienta en la caverna trigeminal&#44; en el suelo de la fosa craneal media&#46; Desde la porci&#243;n distal del ganglio&#44; se divide en tres ramas&#58;</p><p id="par0070" class="elsevierStylePara elsevierViewall">-V1&#58; la rama oft&#225;lmica entra en la &#243;rbita a trav&#233;s de la fisura orbitaria superior&#46; Antes de entrar en ella da sus tres ramas principales&#58; lacrimal&#44; frontal y nasociliar&#46; La rama terminal es el nervio supraorbitario&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">-V2&#58; la rama maxilar es un nervio sensitivo que sale por el agujero redondo mayor&#44; atraviesa la fosa pterigomaxilar y el suelo de la &#243;rbita&#46; Al llegar al agujero infraorbitario&#44; ingresa en la regi&#243;n geniana&#44; donde pasa a llamarse nervio infraorbitario&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">-V3&#58; la rama mandibular nace del ganglio de Gasser como un nervio sensitivo&#59; se dirige hacia el agujero oval&#44; por el que ingresa en la fosa cigom&#225;tica&#46; Durante su paso por este agujero&#44; la ra&#237;z motora del trig&#233;mino se funde a &#233;l&#44; convirti&#233;ndolo as&#237; en nervio mixto&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Su ra&#237;z sensitiva se divide en tres ramas&#58; el nervio auriculotemporal&#44; que se dirige a la gl&#225;ndula par&#243;tida donde se anastomosa con ramas del nervio facial&#59; el nervio lingual&#59; y nervio alveolar inferior&#44; que sale por el agujero mentoniano como nervio mentoniano&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">La ra&#237;z motora se divide en los nervios masticador y milohioideo&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Nervio facial</span><p id="par0095" class="elsevierStylePara elsevierViewall">Es junto con el trig&#233;mino&#44; el que m&#225;s frecuentemente se encuentra implicado&#44; especialmente en casos de CEC que metastatizan en la gl&#225;ndula par&#243;tida&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Emerge del surco bulboprotuberancial&#44; alcanza la cisterna del &#225;ngulo pontocerebeloso&#44; y se introduce en el conducto auditivo interno&#44; en el que se diferencian tres segmentos&#58; laber&#237;ntico&#44; timp&#225;nico y mastoideo&#46; Posteriormente&#44; el nervio facial sale del cr&#225;neo por el agujero estilomastoideo y se introduce en la gl&#225;ndula par&#243;tida donde se divide en dos troncos mayores&#58; cervicofacial&#44; que a su vez se divide en maxilar&#44; mandibular y cervical&#59; y temporofacial&#44; que se divide en dos&#44; rama temporal y rama cigom&#225;tica&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Histolog&#237;a</span><p id="par0105" class="elsevierStylePara elsevierViewall">Los nervios perif&#233;ricos est&#225;n formados por haces de fibras nerviosas&#44; envueltas por tres capas denominadas epineuro&#44; perineuro y endoneuro&#46; El endoneuro es tejido conectivo laxo que rodea cada fibra nerviosa individual&#59; el perineuro es tejido conectivo especializado que rodea cada fasc&#237;culo de fibras nerviosas&#59; y el epineuro es tejido conectivo denso no modelado que rodea todo un nervio perif&#233;rico y llena los espacios entre los fasc&#237;culos nerviosos&#46; El perineuro es el componente principal de la barrera hematoneural y tiene una permeabilidad altamente selectiva&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">En la actualidad no existe una definici&#243;n unificada de IPN&#44; al existir controversia para establecer los criterios histol&#243;gicos&#46; Dunn et al&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">1</span></a> proponen los siguientes hallazgos diagn&#243;sticos&#58; en presencia de una neoplasia maligna&#44; la IPN puede diagnosticarse con la observaci&#243;n de c&#233;lulas citol&#243;gicamente malignas en el espacio perineural de los nervios&#46; En casos ambiguos&#44; es &#250;til la afectaci&#243;n circunferencial total o casi total&#44; as&#237; como la presencia de un seguimiento perineural en las secciones tangenciales y la afectaci&#243;n intraneural&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Por el contrario&#44; Liebig et al&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">4</span></a> afirman que encontrar c&#233;lulas tumorales dentro de cualquiera de las 3 capas de la cubierta del nervio o focos tumorales fuera del nervio con la participaci&#243;n del 33&#37; de la circunferencia del nervio son caracter&#237;sticas suficientes para definir la IPN&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Es importante tener presente que existen simuladores de IPN<a class="elsevierStyleCrossRefs" href="#bib0585"><span class="elsevierStyleSup">42&#8211;44</span></a>&#58; la fibrosis peritumoral&#44; la inflamaci&#243;n perineural&#44; la presencia de epitelio escamoso en &#225;reas de ex&#233;resis previas o el neuroma de las vainas epiteliales&#46; Para establecer el diagn&#243;stico definitivo son muy &#250;tiles las t&#233;cnicas de inmunohistoqu&#237;mica&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Radiolog&#237;a</span><p id="par0125" class="elsevierStylePara elsevierViewall">La resonancia magn&#233;tica es la t&#233;cnica de imagen m&#225;s sensible para diagnosticar la IPN<a class="elsevierStyleCrossRefs" href="#bib0475"><span class="elsevierStyleSup">32&#44;45&#8211;47</span></a>&#46; Al estudiar el trayecto neural en su totalidad&#44; permite evaluar la presencia&#44; as&#237; como la extensi&#243;n de la IPN en aquellos pacientes que presenten signos o s&#237;ntomas de afectaci&#243;n neurol&#243;gica y con ello&#44; planificar la actitud terap&#233;utica&#46; Los hallazgos primarios<a class="elsevierStyleCrossRef" href="#bib0615"><span class="elsevierStyleSup">48</span></a> son&#58; la captaci&#243;n de toda la circunferencia del nervio en las secuencias T1 con gadolinio&#44; el aumento del calibre normal del nervio y la obliteraci&#243;n de planos grasos yuxtaforaminales &#40;<a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall">Se ha descrito como signo indirecto<a class="elsevierStyleCrossRefs" href="#bib0620"><span class="elsevierStyleSup">49&#44;50</span></a> de IPN&#44; la atrofia por denervaci&#243;n cuando existe afectaci&#243;n de una rama motora&#46; Esto se ve en resonancia magn&#233;tica como hiperintensidad de se&#241;al en im&#225;genes T2 con realce en las fases agudas &#40;edema por denervaci&#243;n&#41; y menor volumen muscular e infiltraci&#243;n grasa en las fases tard&#237;as&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Estos signos radiol&#243;gicos pueden persistir indefinidamente a pesar de la mejor&#237;a cl&#237;nica&#44; por tanto&#44; se sospechar&#225; recidiva cuando la lesi&#243;n crezca o progresen los s&#237;ntomas&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">El TAC<a class="elsevierStyleCrossRefs" href="#bib0600"><span class="elsevierStyleSup">45&#44;47</span></a> es menos sensible&#44; sin embargo es muy &#250;til para valorar los cambios &#243;seos&#58; alteraciones en la cortical&#44; forma y tama&#241;o de los for&#225;menes nerviosos&#44; as&#237; como la dilataci&#243;n foraminal y la erosi&#243;n &#243;sea en los casos m&#225;s avanzados&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">El PET<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">51</span></a> es de gran utilidad en los c&#225;nceres de cabeza y cuello&#44; detecta la invasi&#243;n linf&#225;tica&#44; la presencia de met&#225;stasis y de tumor residual o recurrente&#44; pero hasta el momento no existen an&#225;lisis de su sensibilidad para identificar IPN&#44; posiblemente tenga una sensibilidad muy baja&#44; ya que solo detecta recidivas o met&#225;stasis a partir de un determinado tama&#241;o &#40;lesiones mayores de 1&#44;5-2<span class="elsevierStyleHsp" style=""></span>cm en la mayor&#237;a de los casos&#41;&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Si las pruebas de imagen demuestran IPN intracraneal o diseminaci&#243;n perineural&#44; la lesi&#243;n se puede considerar irresecable&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Pron&#243;stico</span><p id="par0155" class="elsevierStylePara elsevierViewall">En ausencia de otros factores de riesgo&#44; si el calibre de los nervios afectos es inferior a 0&#44;1<span class="elsevierStyleHsp" style=""></span>mm y no se encuentra en proximidad al tumor primario&#44; la presencia de IPN no augura un peor pron&#243;stico&#44; por ello no se considera necesaria la terapia adyuvante en estos casos<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">35&#44;36</span></a>&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Campoli<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">9</span></a> revela que aunque la IPN incidental es un hallazgo infrecuente en el CEC&#44; est&#225; asociada con marcadores previos de mal pron&#243;stico&#58; el tama&#241;o del tumor&#44; la profundidad de este&#44; factores de riesgo cl&#237;nico y la extensi&#243;n subcl&#237;nica significativa&#46; Sugiere que la IPN incidental puede servir como marcador para mejorar la precisi&#243;n en la evaluaci&#243;n pron&#243;stica de estos pacientes&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">La invasi&#243;n de nervios m&#225;s gruesos o a distancia del foco principal del tumor<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">35</span></a> independientemente de su di&#225;metro &#40;<a class="elsevierStyleCrossRefs" href="#fig0020">figs&#46; 4 y 5</a>&#41;&#44; implica un peor pron&#243;stico&#46; Clayman et al&#46; objetivaron una supervivencia espec&#237;fica de la enfermedad a 3 a&#241;os del 64&#37; en pacientes con CEC con IPN&#44; frente al 91&#37; para CEC sin IPN<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">40</span></a>&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0170" class="elsevierStylePara elsevierViewall">En una revisi&#243;n sist&#233;mica realizada recientemente a partir de 12 estudios recogiendo 640 CEC con IPN&#44; se determina que no existen diferencias en el riesgo de met&#225;stasis ganglionares o a distancia entre pacientes con IPN microsc&#243;pica y pacientes con IPN cl&#237;nica&#44; sin embargo&#44; estos &#250;ltimos tienen mayor riesgo de recurrencia local y un riesgo de muerte del 30&#37;<a class="elsevierStyleCrossRefs" href="#bib0570"><span class="elsevierStyleSup">37&#8211;39&#44;41</span></a>&#46;</p><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Clasificaci&#243;n zonal</span><p id="par0175" class="elsevierStylePara elsevierViewall">Williams et al&#46;<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">47</span></a> describieron la clasificaci&#243;n zonal para determinar la extensi&#243;n de la IPN a lo largo de los nervios facial y trig&#233;mino en la RMN y con ello la posibilidad de resecci&#243;n quir&#250;rgica&#46; Se distinguen tres zonas&#58; distal &#40;zona 1&#41;&#44; base del cr&#225;neo &#40;zona 2&#41;&#44; cisternal &#40;zona 3&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0180" class="elsevierStylePara elsevierViewall">Esta clasificaci&#243;n ha demostrado ser tambi&#233;n un importante predictor de evoluci&#243;n adversa<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">52</span></a>&#44; con tasas de supervivencia a los 5 a&#241;os del 85&#44;7&#37; para la zona 1&#44; del 64&#44;4&#37; para la zona 2 y del 20&#37; para la zona 3&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Tratamiento</span><p id="par0185" class="elsevierStylePara elsevierViewall">La cirug&#237;a de Mohs<a class="elsevierStyleCrossRefs" href="#bib0640"><span class="elsevierStyleSup">53&#44;54</span></a> se considera la t&#233;cnica de elecci&#243;n para el tratamiento del CECAR&#44; al lograr tasas de recurrencia inferiores&#44; as&#237; como una mayor sensibilidad para la detecci&#243;n de la IPN que la cirug&#237;a est&#225;ndar&#44; ya que permite examinar los m&#225;rgenes laterales y profundos en su totalidad&#44; proporcionando la mejor semejanza de extirpaci&#243;n tumoral completa&#46; Posiblemente la t&#233;cnica m&#225;s empleada es la variante diferida con pieza fijada en formol &#40;<a class="elsevierStyleCrossRef" href="#fig0030">fig&#46; 6</a>&#41;&#46;</p><elsevierMultimedia ident="fig0030"></elsevierMultimedia><p id="par0190" class="elsevierStylePara elsevierViewall">Rowe et al&#46;<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">55</span></a> demostraron tasas de recurrencia local del 47&#37; para la cirug&#237;a convencional y del 0&#37; para la cirug&#237;a de Mohs&#46; Cottel<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">5</span></a> a partir de 17 casos de CEC con IPN tratados con cirug&#237;a de Mohs con un periodo de seguimiento de 42 meses&#44; no recoge ning&#250;n caso de recidiva local y uno de met&#225;stasis &#40;5&#44;9&#37;&#41;&#46; En un estudio retrospectivo con 70 pacientes tratados con cirug&#237;a de Mohs&#44; Leibovitch et al&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">11</span></a> demostraron una tasa de recurrencia del 8&#37; en 5 a&#241;os&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">La presencia de infiltrado inflamatorio entorno a un nervio&#44; al considerarse marcador de IPN&#44; indica la necesidad de continuar estudiando el nervio hasta encontrar c&#233;lulas tumorales o hasta que dicha inflamaci&#243;n desaparece&#46; Incluso&#44; sin que el infiltrado inflamatorio est&#233; presente&#44; se han objetivado en etapas sucesivas&#44; lesiones a distancia&#44; de hasta 14<span class="elsevierStyleHsp" style=""></span>cm m&#225;s all&#225; del sitio inicial del tumor&#44; lo que se conoce como &#171;skip lesions<a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">56</span></a>&#187;&#46; Estas podr&#237;an ser una explicaci&#243;n para la tasa relativamente m&#225;s alta de recidiva posquir&#250;rgica de CEC con IPN en comparaci&#243;n con lesiones sin IPN&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Por ello&#44; algunos investigadores consideran que se deber&#237;a tomar un margen de seguridad adicional con cirug&#237;a de Mohs&#44; incluso despu&#233;s de obtener un margen histol&#243;gico negativo en los casos con IPN<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">11</span></a>&#46; Por el contrario&#44; otros no lo recomiendan&#44; al considerar&#44; que la presencia y localizaci&#243;n de las &#171;skip lesions&#187; son impredecibles y deciden tratar a estos paciente con radioterapia adyuvante&#44; preservando al m&#225;ximo el tejido sano<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">54</span></a>&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Generalmente&#44; la IPN es un hallazgo histol&#243;gico incidental tras la extirpaci&#243;n completa del tumor primario&#46; En los pacientes con m&#225;rgenes quir&#250;rgicos negativos e IPN en peque&#241;os nervios cut&#225;neos &#40;di&#225;metro menor de 0&#44;1<span class="elsevierStyleHsp" style=""></span>mm&#41;&#44; se aconseja realizar seguimiento cl&#237;nico exclusivamente&#46; Ante invasi&#243;n perineural significativa &#40;di&#225;metro superior a 0&#44;1<span class="elsevierStyleHsp" style=""></span>mm&#41; incluso cuando han sido extirpados con m&#225;rgenes quir&#250;rgicos libres&#44; est&#225; indicada la radioterapia adyuvante<a class="elsevierStyleCrossRef" href="#bib0660"><span class="elsevierStyleSup">57</span></a>&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">En aquellos pacientes con IPN cl&#237;nica es fundamental realizar una evaluaci&#243;n exhaustiva de los signos y s&#237;ntomas de IPN durante el examen cl&#237;nico pretratamiento&#44; as&#237; como un abordaje terap&#233;utico agresivo&#44; para minimizar el riesgo de recidiva tumoral y met&#225;stasis&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">Si mediante las pruebas de imagen se considera posible la resecabilidad del tumor primario se aboga por la resecci&#243;n quir&#250;rgica agresiva seguida de radioterapia&#46; La red nacional de estudio del c&#225;ncer &#40;NCCN&#41; recomienda en su &#250;ltima actualizaci&#243;n del a&#241;o 2017 la radioterapia adyuvante en aquellos CEC con invasi&#243;n perineural extensa&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">En los casos en los que no sea posible&#58; enfermedad en la zona 3&#44; IPN cerca o dentro de la cavidad craneal o aquellos tumores que extienden a lo largo de un nervio craneal a la base del cr&#225;neo&#44; la radioterapia est&#225; indicada&#44; con intenci&#243;n paliativa&#44; reduci&#233;ndose considerablemente las posibilidades de curar a estos pacientes&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">Actualmente&#44; no hay estudios prospectivos que confirmen la eficacia de agregar quimioterapia en pacientes con CEC con IPN<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">29</span></a>&#46; Se est&#225;n realizando ensayos cl&#237;nicos con un anticuerpo monoclonal anti-PD1 en pacientes con CEC metast&#225;sicos o localmente avanzados&#44; ser&#237;a interesante evaluar su utilidad como terapia adyuvante en pacientes con IPN para minimizar el riesgo de recurrencia local y met&#225;stasis<a class="elsevierStyleCrossRefs" href="#bib0665"><span class="elsevierStyleSup">58&#8211;61</span></a><span class="elsevierStyleItalic">&#46;</span></p></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Seguimiento</span><p id="par0230" class="elsevierStylePara elsevierViewall">Debido a la alta agresividad y a las altas tasas de recurrencias&#44; es fundamental realizar un control estricto en aquellos pacientes con IPN significativa&#44; siendo los primeros 24 meses&#44; el per&#237;odo de mayor riesgo de recurrencia local&#44; realizando rutinariamente una exploraci&#243;n minuciosa del nervio trig&#233;mino y facial&#44; as&#237; como de la movilidad ocular<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">62</span></a>&#46; Adem&#225;s&#44; se aconseja la realizaci&#243;n de RMN semestrales&#46; Si bien es cierto que la utilidad de la vigilancia radiol&#243;gica no ha sido bien cuantificada&#44; la detecci&#243;n precoz y con ella el retratamiento&#44; permiten aumentar la supervivencia en estos pacientes&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conclusiones</span><p id="par0235" class="elsevierStylePara elsevierViewall">Debido a la implicaci&#243;n pron&#243;stica de la IPN en el CEC&#44; resulta fundamental su detecci&#243;n precoz&#44; por ello&#44; realizar una exploraci&#243;n cl&#237;nica minuciosa&#44; un estudio histol&#243;gico y radiol&#243;gico exhaustivo&#44; as&#237; como protocolos de seguimiento&#44; es esencial para optimizar el manejo terap&#233;utico de estos pacientes&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Financiaci&#243;n</span><p id="par0240" class="elsevierStylePara elsevierViewall">&#40;2017-172-001&#41; Universidad Cat&#243;lica de Valencia&#44; ayudas internas investigaci&#243;n UCV&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflicto de intereses</span><p id="par0245" class="elsevierStylePara elsevierViewall">Los autores declaran no tener ning&#250;n conflicto de intereses&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:14 [
        0 => array:3 [
          "identificador" => "xres1214695"
          "titulo" => "Graphical abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0005"
            ]
          ]
        ]
        1 => array:3 [
          "identificador" => "xres1214693"
          "titulo" => "Resumen"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0010"
            ]
          ]
        ]
        2 => array:2 [
          "identificador" => "xpalclavsec1130592"
          "titulo" => "Palabras clave"
        ]
        3 => array:3 [
          "identificador" => "xres1214694"
          "titulo" => "Abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0015"
            ]
          ]
        ]
        4 => array:2 [
          "identificador" => "xpalclavsec1130591"
          "titulo" => "Keywords"
        ]
        5 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introducci&#243;n"
        ]
        6 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Epidemiolog&#237;a"
        ]
        7 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Patog&#233;nesis"
        ]
        8 => array:3 [
          "identificador" => "sec0020"
          "titulo" => "Diagn&#243;stico"
          "secciones" => array:6 [
            0 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Clasificaci&#243;n de la infiltraci&#243;n perineural"
            ]
            1 => array:3 [
              "identificador" => "sec0030"
              "titulo" => "Anatom&#237;a de los nervios de la regi&#243;n facial"
              "secciones" => array:2 [
                0 => array:2 [
                  "identificador" => "sec0035"
                  "titulo" => "Nervio trig&#233;mino"
                ]
                1 => array:2 [
                  "identificador" => "sec0040"
                  "titulo" => "Nervio facial"
                ]
              ]
            ]
            2 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Histolog&#237;a"
            ]
            3 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Radiolog&#237;a"
            ]
            4 => array:3 [
              "identificador" => "sec0055"
              "titulo" => "Pron&#243;stico"
              "secciones" => array:1 [
                0 => array:2 [
                  "identificador" => "sec0060"
                  "titulo" => "Clasificaci&#243;n zonal"
                ]
              ]
            ]
            5 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "Tratamiento"
            ]
          ]
        ]
        9 => array:2 [
          "identificador" => "sec0070"
          "titulo" => "Seguimiento"
        ]
        10 => array:2 [
          "identificador" => "sec0075"
          "titulo" => "Conclusiones"
        ]
        11 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Financiaci&#243;n"
        ]
        12 => array:2 [
          "identificador" => "sec0085"
          "titulo" => "Conflicto de intereses"
        ]
        13 => array:1 [
          "titulo" => "Bibliograf&#237;a"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2018-08-05"
    "fechaAceptado" => "2018-10-01"
    "PalabrasClave" => array:2 [
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1130592"
          "palabras" => array:4 [
            0 => "Carcinoma epidermoide"
            1 => "Infiltraci&#243;n perineural"
            2 => "Alto riesgo"
            3 => "Radioterapia"
          ]
        ]
      ]
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1130591"
          "palabras" => array:4 [
            0 => "Squamous cell carcinoma"
            1 => "Perineural infiltration"
            2 => "High risk"
            3 => "Radiotherapy"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">En ocasiones el carcinoma epidermoide cut&#225;neo se caracteriza por tener un mayor riesgo de desarrollar recurrencia locorregional y ocasionalmente met&#225;stasis a distancia&#46; Existen diversos factores cl&#237;nico-patol&#243;gicos de reconocido valor pron&#243;stico&#44; entre ellos la presencia de infiltraci&#243;n perineural&#46; Esta consiste en la diseminaci&#243;n de c&#233;lulas tumorales a trav&#233;s de los nervios&#44; siendo en la mayor&#237;a de los casos un hallazgo incidental&#46; Cuando aparecen s&#237;ntomas y&#47;o evidencia radiol&#243;gica de la extensi&#243;n de la infiltraci&#243;n perineural&#44; se clasifica como infiltraci&#243;n perineural cl&#237;nica y se asocia a un mayor riesgo de recurrencia local y de mortalidad&#46;</p></span>"
      ]
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0015" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Cutaneous squamous cell carcinoma is sometimes characterized by an increased risk of locoregional recurrence and occasionally distant metastasis&#46; Several clinical and pathological factors&#44; including perineural invasion&#44; have been shown to have prognostic value in this setting&#46; Perineural invasion&#44; that is&#44; the spread of tumor cells into the space surrounding a nerve&#44; is usually an incidental finding&#46; In the presence of symptoms or radiographic evidence of perineural spread&#44; the diagnosis is clinical perineural invasion&#44; which is associated with an increased risk of local recurrence and mortality&#46;</p></span>"
      ]
    ]
    "multimedia" => array:8 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figura 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 620
            "Ancho" => 900
            "Tamanyo" => 66272
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">IPN cl&#237;nica&#58; nervio supraorbitario engrosado&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figura 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 525
            "Ancho" => 1400
            "Tamanyo" => 81906
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">IPN cl&#237;nica del nervio facial&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Figura 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 1975
            "Ancho" => 2500
            "Tamanyo" => 1458100
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">IPN significativa&#58; di&#225;metro del nervio superior a 0&#44;1 mm&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "fig0020"
        "etiqueta" => "Figura 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 2149
            "Ancho" => 2500
            "Tamanyo" => 1249360
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">IPN en nervios de calibre inferior a 0&#44;1 mm&#44; pero a distancia del foco principal del tumor&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "fig0025"
        "etiqueta" => "Figura 5"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr5.jpeg"
            "Alto" => 2924
            "Ancho" => 2500
            "Tamanyo" => 592353
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">IPN de la rama maxilar &#40;V2&#41;&#46;</p>"
        ]
      ]
      5 => array:7 [
        "identificador" => "fig0030"
        "etiqueta" => "Figura 6"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr6.jpeg"
            "Alto" => 1358
            "Ancho" => 2169
            "Tamanyo" => 135326
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Algoritmo terap&#233;utico del CEC con IPN&#46;</p>"
        ]
      ]
      6 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Tabla 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Tabla "
            "rol" => "short"
          ]
        ]
        "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=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Zona 1</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>V1&#58; hasta la fisura orbitaria superior&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>V2&#58; hasta la apertura externa del foramen redondo mayor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>V3&#58; hasta la apertura externa del foramen oval&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>VII&#58; hasta la apertura externa del forman estilomastoideo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Zona 2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>V1&#44; V2 y V3&#58; desde la zona 1 al ganglio de Gasser&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>VII&#58; desde la zona 1 al extremo lateral del CAI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Zona 3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Todo el nervio desde el ganglio de Gasser o CAI hasta las cisternas o tronco del enc&#233;falo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2073718.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Clasificaci&#243;n zonal para IPN en tumores de cabeza y cuello</p>"
        ]
      ]
      7 => array:5 [
        "identificador" => "fig0035"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "fx1.jpeg"
            "Alto" => 985
            "Ancho" => 1333
            "Tamanyo" => 210478
          ]
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "Bibliograf&#237;a"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:62 [
            0 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Perineural invasion&#58; identification&#44; significance&#44; and a standardized definition"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46; Dunn"
                            1 => "M&#46;B&#46; Morgan"
                            2 => "T&#46;W&#46; Beer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1524-4725.2008.34412.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Dermatol Surg"
                        "fecha" => "2009"
                        "volumen" => "35"
                        "paginaInicial" => "214"
                        "paginaFinal" => "221"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19215258"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0325"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Maladies des nerfs"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "J&#46; Cruveilhier"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:6 [
                        "editores" => "J&#46;Cruveilhier"
                        "titulo" => "Anatomie Pathologique du Corps Humain&#46;"
                        "paginaInicial" => "1"
                        "paginaFinal" => "3"
                        "edicion" => "2&#46;<span class="elsevierStyleHsp" style=""></span>nd ed&#46;"
                        "serieFecha" => "1835"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Perineural invasion and spread in head and neck cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46; Johnston"
                            1 => "E&#46; Yu"
                            2 => "J&#46; Kim"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1586/era.12.9"
                      "Revista" => array:6 [
                        "tituloSerie" => "Expert Rev Anticancer Ther&#46;"
                        "fecha" => "2012"
                        "volumen" => "12"
                        "paginaInicial" => "359"
                        "paginaFinal" => "371"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22369327"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Perineural invasion in cancer&#58; a review of the literature"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "C&#46; Liebig"
                            1 => "G&#46; Ayala"
                            2 => "J&#46;A&#46; Wilks"
                            3 => "D&#46;H&#46; Berger"
                            4 => "D&#46; Albo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/cncr.24396"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cancer"
                        "fecha" => "2009"
                        "volumen" => "115"
                        "paginaInicial" => "3379"
                        "paginaFinal" => "3391"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19484787"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0340"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Perineural invasion by squamous cell carcinoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "W&#46;I&#46; Cottel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Dermatol Surg Oncol"
                        "fecha" => "1982"
                        "volumen" => "2"
                        "paginaInicial" => "589"
                        "paginaFinal" => "600"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0345"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Squamous cell carcinoma of the skin &#40;excluding lip and oral mucosa&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "T&#46;M&#46; Johnson"
                            1 => "D&#46;E&#46; Rowe"
                            2 => "B&#46;R&#46; Nelson"
                            3 => "N&#46;A&#46; Swanson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Am Acad Dermatol"
                        "fecha" => "1992"
                        "volumen" => "6"
                        "paginaInicial" => "467"
                        "paginaFinal" => "484"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0350"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Perineural invasion of cutaneous malignancies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46;M&#46; Feasel"
                            1 => "T&#46;J&#46; Brown"
                            2 => "M&#46; Bogle"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Dermatol Surg"
                        "fecha" => "2001"
                        "volumen" => "27"
                        "paginaInicial" => "531"
                        "paginaFinal" => "542"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0355"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Squamous cell carcinoma of the skin with perineural invasion"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "N&#46; Lawrence"
                            1 => "W&#46;I&#46; Cottel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Acad Dermatol"
                        "fecha" => "1994"
                        "volumen" => "31"
                        "paginaInicial" => "30"
                        "paginaFinal" => "33"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8021368"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0515"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A prospective evaluation of the clinical&#44; histologic&#44; and therapeutic variables associated with incidental perineural invasion in cutaneous squamous cell carcinoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46; Campoli"
                            1 => "D&#46;G&#46; Brodland"
                            2 => "J&#46; Zitelli"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Am Acad Dermatol&#46;"
                        "fecha" => "2014"
                        "volumen" => "70"
                        "paginaInicial" => "630"
                        "paginaFinal" => "636"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0365"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Perineural spreads by squamous carcinomas of the head and neck&#58; a morphological study using antiaxonal and antimyelin monoclonal antibodies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "R&#46;L&#46; Carter"
                            1 => "C&#46;S&#46; Foster"
                            2 => "E&#46;A&#46; Dinsdale"
                            3 => "M&#46;R&#46; Pittam"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/jcp.36.3.269"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Pathol"
                        "fecha" => "1983"
                        "volumen" => "36"
                        "paginaInicial" => "269"
                        "paginaFinal" => "275"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6338053"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0520"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cutaneous squamous cell carcinoma treated with Mohs micrographic surgery in Australia II Perineural invasion"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "I&#46; Leibovitch"
                            1 => "S&#46;C&#46; Huilgol"
                            2 => "D&#46; Selva"
                            3 => "D&#46; Hill"
                            4 => "S&#46; Richards"
                            5 => "R&#46; Paver"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Am Acad Dermatol&#46;"
                        "fecha" => "2005"
                        "volumen" => "53"
                        "paginaInicial" => "261"
                        "paginaFinal" => "266"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0525"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Morphology of peripheral nerves&#44; their sheaths&#44; and their vascularisation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46;A&#46; Reina"
                            1 => "A&#46; Lopez"
                            2 => "M&#46;C&#46; Villanueva"
                            3 => "J&#46;A&#46; de Andr&#233;s"
                            4 => "G&#46;I&#46; Le&#243;n"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Esp Anestesiol Reanim&#46;"
                        "fecha" => "2000"
                        "volumen" => "47"
                        "paginaInicial" => "464"
                        "paginaFinal" => "475"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11171467"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0530"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Perineural invasion in oral squamous cell carcinoma&#58;&#46;a discussion of significance and review of the literature"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "N&#46;O&#46; Binmadi"
                            1 => "J&#46;R&#46; Basile"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Oral Oncol&#46;"
                        "fecha" => "2011"
                        "volumen" => "47"
                        "paginaInicial" => "1005"
                        "paginaFinal" => "1010"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0385"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mechanisms of perineural invasion"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "L&#46; Richard Bakst"
                            1 => "J&#46; Richard Wong"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Neurol Surg B"
                        "fecha" => "2016"
                        "volumen" => "77"
                        "paginaInicial" => "96"
                        "paginaFinal" => "106"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0390"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nerve growth factor and tyrosine kinase A receptor in oral squamous cell carcinoma&#58; is there an association with perineural invasion&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46; Kolokythas"
                            1 => "D&#46;P&#46; Cox"
                            2 => "N&#46; Dekker"
                            3 => "B&#46;L&#46; Schmidt"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.joms.2010.01.006"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Oral Maxillofac Surg"
                        "fecha" => "2010"
                        "volumen" => "68"
                        "paginaInicial" => "1290"
                        "paginaFinal" => "1295"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20363547"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0395"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Correlation of neural cell adhesion molecules with perineural spread of squamous cell carcinoma of the head and neck"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "E&#46; Vural"
                            1 => "J&#46; Hutcheson"
                            2 => "S&#46; Korourian"
                            3 => "S&#46; Kechelava"
                            4 => "E&#46; Hanna"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0194-5998(00)70203-8"
                      "Revista" => array:6 [
                        "tituloSerie" => "Otolaryngol Head Neck Surg"
                        "fecha" => "2000"
                        "volumen" => "122"
                        "paginaInicial" => "717"
                        "paginaFinal" => "720"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10793353"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0400"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nerve cell adhesion molecule expression in squamous cell carcinoma of the head and neck&#58; a predictor of propensity toward perineural spread"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;B&#46; McLaughlin Jr&#46;"
                            1 => "K&#46;T&#46; Montone"
                            2 => "S&#46;J&#46; Wall"
                            3 => "A&#46;A&#46; Chalian"
                            4 => "G&#46;S&#46; Weinstein"
                            5 => "S&#46;A&#46; Roberts"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Laryngoscope&#46;"
                        "fecha" => "1999"
                        "volumen" => "109"
                        "paginaInicial" => "821"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10334238"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0405"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The semaphorins"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "U&#46; Yazdani"
                            1 => "J&#46;R&#46; Terman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Gen Biol"
                        "fecha" => "2006"
                        "volumen" => "7"
                        "paginaInicial" => "211"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0535"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Binmadi NO&#44; Yang Y&#44; Zhou H&#44; Proia P&#44; Lin YL&#44; Batista de Paula AM&#44; et al&#46; Plexin-B1 and semaphorin 4<span class="elsevierStyleHsp" style=""></span>D cooperate to promote perineural invasion in a RhoA&#47;ROK-dependent manner&#46; Am J Pathol&#46; 1203&#59;180&#58;1232-42&#46;"
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0415"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Perineural spread in head and neck skin cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "M&#46;J&#46; Veness"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Australas J Dermatol&#46;"
                        "fecha" => "2000"
                        "volumen" => "41"
                        "paginaInicial" => "117"
                        "paginaFinal" => "119"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10812708"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0540"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Carcinoma of the skin of the head and neck with perineural invasion"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "W&#46;M&#46; Mendenhall"
                            1 => "J&#46;T&#46; Parsons"
                            2 => "N&#46;P&#46; Mendenhall"
                            3 => "T&#46;A&#46; Brant"
                            4 => "S&#46;P&#46; Stringer"
                            5 => "N&#46;J&#46; Cassisi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Head Neck&#46;"
                        "fecha" => "1989"
                        "volumen" => "11"
                        "paginaInicial" => "301"
                        "paginaFinal" => "308"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0545"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Perineural invasion in skin cancer of the head and neck&#58; a review of nine cases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "F&#46;L&#46; Ampil"
                            1 => "J&#46;C&#46; Hardin"
                            2 => "S&#46;P&#46; Peskind"
                            3 => "F&#46;J&#46; Stucker"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Oral Maxillofac Surg&#46;"
                        "fecha" => "1995"
                        "volumen" => "53"
                        "paginaInicial" => "34"
                        "paginaFinal" => "38"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7799119"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0550"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Carcinoma of the skin with perineural invasion"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Garcia-Serra"
                            1 => "R&#46;W&#46; Hinerman"
                            2 => "W&#46;M&#46; Mendenhall"
                            3 => "R&#46;J&#46; Amdur"
                            4 => "C&#46;G&#46; Morris"
                            5 => "L&#46;S&#46; Williams"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hed.10334"
                      "Revista" => array:6 [
                        "tituloSerie" => "Head Neck&#46;"
                        "fecha" => "2003"
                        "volumen" => "25"
                        "paginaInicial" => "1027"
                        "paginaFinal" => "1033"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14648861"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0555"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Impact of Radiographic Findings on For Prognosis Skin Cancer With Perineural Invasion"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46;J&#46; Balamucki"
                            1 => "R&#46; Dejesus"
                            2 => "T&#46;J&#46; Galloway"
                            3 => "A&#46;A&#46; Mancuso"
                            4 => "R&#46;J&#46; Amdur"
                            5 => "C&#46;G&#46; Morris"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/COC.0b013e3182940ddf"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Clin Oncol&#46;"
                        "fecha" => "2015"
                        "volumen" => "38"
                        "paginaInicial" => "248"
                        "paginaFinal" => "251"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23648439"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0440"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Facial and trigeminal neural dysfunction by a primary cutaneous squamous cell carcinoma&#58; MRI and clinicopathologic correlates"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46;J&#46; Gulya"
                            1 => "R&#46; Scher"
                            2 => "A&#46; Schwartz"
                            3 => "W&#46;R&#46; Wilson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Otol&#46;"
                        "fecha" => "1992"
                        "volumen" => "13"
                        "paginaInicial" => "587"
                        "paginaFinal" => "590"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1449189"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0445"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treatment recommendations in patients diagnosed with high-risk cutaneous squamous cell carcinoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "M&#46;J&#46; Veness"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1440-1673.2005.01496.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Australas Radiol&#46;"
                        "fecha" => "2005"
                        "volumen" => "49"
                        "paginaInicial" => "365"
                        "paginaFinal" => "376"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16174174"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0450"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Perineural spread of cutaneous squamous cell carcinoma manifesting as ophthalmoplegia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46; Koukkoulli"
                            1 => "N&#46; Koutroumanos"
                            2 => "D&#46; Kidd"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3109/01658107.2015.1035449"
                      "Revista" => array:6 [
                        "tituloSerie" => "Neuroophthalmology&#46;"
                        "fecha" => "2015"
                        "volumen" => "39"
                        "paginaInicial" => "144"
                        "paginaFinal" => "146"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27928347"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0455"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Perineural spread of facial squamous cell carcinoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46;H&#46; Nogajski"
                            1 => "J&#46; Brewer"
                            2 => "C&#46;E&#46; Storey"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Clin Neurosci"
                        "fecha" => "2006"
                        "volumen" => "16"
                        "paginaInicial" => "400"
                        "paginaFinal" => "403"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0460"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Skin cancer of the head and neck with perineural invasion"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "W&#46;M&#46; Mendenhall"
                            1 => "R&#46;J&#46; Amdur"
                            2 => "R&#46;W&#46; Hinerman"
                            3 => "J&#46;W&#46; Werning"
                            4 => "R&#46;S&#46; Malyapa"
                            5 => "D&#46;B&#46; Villaret"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/01.coc.0000251224.16075.60"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Clin Oncol&#46;"
                        "fecha" => "2007 Feb"
                        "volumen" => "30"
                        "paginaInicial" => "93"
                        "paginaFinal" => "96"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17278901"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0465"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A rare case of acral cutaneous squamous cell carcinoma with multiple late cutaneous metastases and extensive neurotropic spread"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "E&#46; Lowe"
                            1 => "T&#46; Brown"
                            2 => "W&#46;A&#46; Geary"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "JAAD Case Rep&#46;"
                        "fecha" => "2016"
                        "volumen" => "2"
                        "paginaInicial" => "34"
                        "paginaFinal" => "36"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0560"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Perineural spread of squamous cell carcinoma&#58; from skin to skin through the brachial plexus"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "S&#46; Capek"
                            1 => "K&#46; Amrami"
                            2 => "B&#46; Howe"
                            3 => "D&#46;R&#46; Salomao"
                            4 => "P&#46;J&#46; Dyck"
                            5 => "R&#46;J&#46; Spinner"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.clineuro.2014.11.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Neurol Neurosurg&#46;"
                        "fecha" => "2015"
                        "volumen" => "128"
                        "paginaInicial" => "90"
                        "paginaFinal" => "93"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25462103"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0475"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Perineural invasion of skin cancers in the head and neck&#58; an uncommon phenomenon revisited"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "S&#46; Gaddikeri"
                            1 => "A&#46; Bhrany"
                            2 => "Y&#46; Anzai"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Otolaryngology"
                        "fecha" => "2014"
                        "volumen" => "4"
                        "paginaInicial" => "169"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0480"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Intracranial management of perineural spread in the trigeminal nerve"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46;J&#46; Redmond"
                            1 => "B&#46;J&#46; Panizza"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1055/s-0036-1571838"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Neurol Surg B Skull Base&#46;"
                        "fecha" => "2016"
                        "volumen" => "77"
                        "paginaInicial" => "150"
                        "paginaFinal" => "160"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27123391"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0485"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Imaging the trigeminal nerve"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46; Borges"
                            1 => "J&#46; Casselman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ejrad.2010.02.006"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Radiol&#46;"
                        "fecha" => "2010"
                        "volumen" => "74"
                        "paginaInicial" => "323"
                        "paginaFinal" => "340"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20227216"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0565"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:1 [
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:4 [
                        "editores" => "M&#46;B&#46;Amin, S&#46;Edge, F&#46;Greene, D&#46;R&#46;Byrd, R&#46;K&#46;Brookland, M&#46;K&#46;Washington"
                        "titulo" => "AJCC Cancer Staging Manual"
                        "edicion" => "8<span class="elsevierStyleHsp" style=""></span>th ed&#46;"
                        "serieFecha" => "2017"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0495"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Outcomes of primary cutaneous squamous cell carcinoma with perineural invasion&#58; an 11-year cohort study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "J&#46;B&#46; Carter"
                            1 => "M&#46;M&#46; Johnson"
                            2 => "T&#46;L&#46; Chua"
                            3 => "P&#46;S&#46; Karia"
                            4 => "C&#46;D&#46; Schmults"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jamadermatol.2013.746"
                      "Revista" => array:7 [
                        "tituloSerie" => "JAMA Dermatol&#46;"
                        "fecha" => "2013 Jan"
                        "volumen" => "149"
                        "paginaInicial" => "35"
                        "paginaFinal" => "41"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23324754"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0022347613008147"
                          "estado" => "S300"
                          "issn" => "00223476"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0570"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma&#58; a prospective study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46;D&#46; Brantsch"
                            1 => "C&#46; Meisner"
                            2 => "B&#46; Schonfisch"
                            3 => "B&#46; Trilling"
                            4 => "J&#46; Wehner-Caroli"
                            5 => "M&#46; R&#246;cken"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S1470-2045(08)70178-5"
                      "Revista" => array:7 [
                        "tituloSerie" => "Lancet Oncol&#46;"
                        "fecha" => "2008"
                        "volumen" => "9"
                        "paginaInicial" => "713"
                        "paginaFinal" => "720"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18617440"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0735109717409971"
                          "estado" => "S300"
                          "issn" => "07351097"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0505"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Factors predictive of recurrence and death from cutaneous squamous cell carcinoma&#58; a 10-year&#44; single-institution cohort study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "C&#46;D&#46; Schmults"
                            1 => "P&#46;S&#46; Karia"
                            2 => "J&#46;B&#46; Carter"
                            3 => "J&#46; Han"
                            4 => "A&#46;A&#46; Qureshi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "JAMA Dermatol&#46;"
                        "fecha" => "2013"
                        "volumen" => "149"
                        "paginaInicial" => "541"
                        "paginaFinal" => "547"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0510"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sentinel lymph node biopsy in cutaneous squamous cell carcinoma&#58; a systematic review of the English literature"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46;S&#46; Ross"
                            1 => "C&#46;D&#46; Schmults"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1524-4725.2006.32300.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Dermatol Surg&#46;"
                        "fecha" => "2006"
                        "volumen" => "32"
                        "paginaInicial" => "1309"
                        "paginaFinal" => "1321"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17083582"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0575"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mortality risk from squamous cell skin cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46;L&#46; Clayman"
                            1 => "J&#46;J&#46; Lee"
                            2 => "F&#46;C&#46; Holsinger"
                            3 => "X&#46; Zhou"
                            4 => "M&#46; Duvic"
                            5 => "A&#46;K&#46; El-Naggar"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2005.02.155"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol&#46;"
                        "fecha" => "2005"
                        "volumen" => "23"
                        "paginaInicial" => "759"
                        "paginaFinal" => "765"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15681519"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0580"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical and incidental perineural invasion of cutaneous squamous cell carcinoma&#58; A systematic review and pooled analysis of outcomes data"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "P&#46;S&#46; Karia"
                            1 => "F&#46;C&#46; Morgan"
                            2 => "E&#46;S&#46; Ruiz"
                            3 => "C&#46;D&#46; Schmults"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jamadermatol.2017.1680"
                      "Revista" => array:6 [
                        "tituloSerie" => "JAMA Dermatol"
                        "fecha" => "2017"
                        "volumen" => "153"
                        "paginaInicial" => "781"
                        "paginaFinal" => "788"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28678985"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0585"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Peritumoral fibrosis in basal cell and squamous cell carcinoma mimicking perineural invasion&#58; potential pitfall in Mohs micrographic surgery"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46;M&#46; Hassanein"
                            1 => "S&#46;A&#46; Proper"
                            2 => "N&#46;D&#46; Depcik-Smith"
                            3 => "F&#46;P&#46; Flowers"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Dermatol Surg"
                        "fecha" => "2005"
                        "volumen" => "31"
                        "paginaInicial" => "1101"
                        "paginaFinal" => "1106"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16164857"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0590"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Histologic mimics of perineural invasion"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46; Dunn"
                            1 => "M&#46;B&#46; Morgan"
                            2 => "T&#46;W&#46; Beer"
                            3 => "K&#46;T&#46; Chen"
                            4 => "S&#46;M&#46; Acker"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1600-0560.2008.01197.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Cutan Pathol&#46;"
                        "fecha" => "2009"
                        "volumen" => "36"
                        "paginaInicial" => "937"
                        "paginaFinal" => "942"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19210583"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0595"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical value of paraffin sections in association with Mohs micrographic surgery for nonmelanoma skin cancers"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "T&#46;L&#46; Ebede"
                            1 => "E&#46;H&#46; Lee"
                            2 => "S&#46;W&#46; Dusza"
                            3 => "K&#46;J&#46; Busam"
                            4 => "K&#46;S&#46; Nehal"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1524-4725.2012.02570.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Dermatol Surg&#46;"
                        "fecha" => "2012"
                        "volumen" => "38"
                        "paginaInicial" => "1631"
                        "paginaFinal" => "1638"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22958072"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0600"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Perineural spread in head and neck tumors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "B&#46; Brea &#193;lvarez"
                            1 => "M&#46; Tu&#241;&#243;n G&#243;mez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.rx.2014.04.006"
                      "Revista" => array:6 [
                        "tituloSerie" => "Radiolog&#237;a&#46;"
                        "fecha" => "2014"
                        "volumen" => "56"
                        "paginaInicial" => "400"
                        "paginaFinal" => "412"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25002354"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0605"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Impact of radiographic findings on prognosis for skin carcinoma with clinical perineural invasion"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "T&#46;J&#46; Galloway"
                            1 => "C&#46;G&#46; Morris"
                            2 => "A&#46;A&#46; Mancuso"
                            3 => "R&#46;J&#46; Amdur"
                            4 => "W&#46;M&#46; Mendenhall"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Cancer&#46;"
                        "fecha" => "2005"
                        "volumen" => "103"
                        "paginaInicial" => "1254"
                        "paginaFinal" => "1257"
                        "itemHostRev" => array:3 [
                          "pii" => "S073510971401660X"
                          "estado" => "S300"
                          "issn" => "07351097"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0610"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Perineural spreads of cutaneous squamous and basal cell carcinoma&#58; CT and MR detections and its impact on patient management and prognosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "L&#46;S&#46; Williams"
                            1 => "A&#46;A&#46; Mancuso"
                            2 => "W&#46;M&#46; Mendenhall"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Int J Radiat Biol Phys"
                        "fecha" => "2001"
                        "volumen" => "49"
                        "paginaInicial" => "1061"
                        "paginaFinal" => "1069"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0615"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Identification of juxtaforaminal fat pads of the second division of the trigeminal pathway on MRI and CT"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46; Yamamoto"
                            1 => "H&#46;D&#46; Curtin"
                            2 => "P&#46; Suwansa-ard"
                            3 => "O&#46; Sakai"
                            4 => "T&#46; Sano"
                            5 => "T&#46; Okano"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2214/ajr.182.2.1820385"
                      "Revista" => array:6 [
                        "tituloSerie" => "AJR Am J Roentgenol&#46;"
                        "fecha" => "2004"
                        "volumen" => "182"
                        "paginaInicial" => "385"
                        "paginaFinal" => "392"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14736668"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib0620"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Magnetic resonance imaging of perineural spread of head and neck malignancies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "D&#46; Gandhi"
                            1 => "S&#46; Gujar"
                            2 => "S&#46;K&#46; Mukherji"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Top Magn Reson Imaging&#46;"
                        "fecha" => "2004"
                        "volumen" => "15"
                        "paginaInicial" => "79"
                        "paginaFinal" => "85"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15269610"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib0625"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "MR Imaging in two cases of subacute denervation change in the muscles of facial expression"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "N&#46;J&#46; Fischbein"
                            1 => "M&#46;J&#46; Kaplan"
                            2 => "R&#46;K&#46; Jackler"
                            3 => "W&#46;P&#46; Dillon"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "AJNR Am J Neuroradiol&#46;"
                        "fecha" => "2001"
                        "volumen" => "22"
                        "paginaInicial" => "880"
                        "paginaFinal" => "884"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib0630"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fluorodeoxyglucose positron emission tomography in cutaneous squamous cell carcinoma&#58; retrospective analysis of 12 patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "S&#46;B&#46; Cho"
                            1 => "W&#46;G&#46; Chung"
                            2 => "M&#46; Yun"
                            3 => "J&#46;D&#46; Lee"
                            4 => "M&#46;G&#46; Lee"
                            5 => "K&#46;Y&#46; Chung"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Dermatol Surg&#46;"
                        "fecha" => "2005"
                        "volumen" => "31"
                        "paginaInicial" => "442"
                        "paginaFinal" => "447"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15871320"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib0635"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemiology of clinical perineural invasion in cutaneous squamous cell carcinoma of the head and neck"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "C&#46;A&#46; Solares"
                            1 => "K&#46; Lee"
                            2 => "P&#46; Parmar"
                            3 => "P&#46; O&#8217;Rourke"
                            4 => "B&#46; Panizza"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/0194599811434897"
                      "Revista" => array:6 [
                        "tituloSerie" => "Otolaryngol Head Neck Surg&#46;"
                        "fecha" => "2012"
                        "volumen" => "146"
                        "paginaInicial" => "746"
                        "paginaFinal" => "751"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22275189"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib0640"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cutaneous squamous cell carcinoma with perineural invasion&#58; A case report and review of the literature"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "C&#46;C&#46; Adams"
                            1 => "B&#46; Thomas"
                            2 => "J&#46;L&#46; Bingham"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Cutis&#46;"
                        "fecha" => "2014"
                        "volumen" => "93"
                        "paginaInicial" => "141"
                        "paginaFinal" => "144"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24738095"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib0645"
              "etiqueta" => "54"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treatment of cutaneous squamous cell carcinoma with perineural invasion using Mohs micrographic surgery&#58; report of two cases and review of the literature"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "R&#46;B&#46; Reule"
                            1 => "N&#46;J&#46; Golda"
                            2 => "R&#46;G&#46; Wheeland"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1524-4725.2009.01276.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Dermatol Surg&#46;"
                        "fecha" => "2009"
                        "volumen" => "35"
                        "paginaInicial" => "1559"
                        "paginaFinal" => "1566"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19681994"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib0650"
              "etiqueta" => "55"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prognostic factors for local recurrence&#44; metastasis&#44; and survival rates in squamous cell carcinoma of the skin&#44; ear&#44; and lip"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "D&#46;E&#46; Rowe"
                            1 => "F&#46;J&#46; Carroll"
                            2 => "C&#46;L&#46; Day"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Acad Dermatol"
                        "fecha" => "1992"
                        "volumen" => "26"
                        "paginaInicial" => "976"
                        "paginaFinal" => "990"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1607418"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            55 => array:3 [
              "identificador" => "bib0655"
              "etiqueta" => "56"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The extension of cancer of the head and neck through peripheral nerves"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46;J&#46; Ballantyne"
                            1 => "A&#46;B&#46; McCarten"
                            2 => "M&#46;L&#46; Ibanez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/0002-9610(63)90074-6"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Surg&#46;"
                        "fecha" => "1963"
                        "volumen" => "106"
                        "paginaInicial" => "651"
                        "paginaFinal" => "667"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14070757"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            56 => array:3 [
              "identificador" => "bib0660"
              "etiqueta" => "57"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "What is the role of adjuvant radiotherapy in the treatment of cutaneous squamous cell carcinoma with perineural invasion&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46; Han"
                            1 => "D&#46; Ratner"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Cancer"
                        "fecha" => "2007"
                        "volumen" => "109"
                        "paginaInicial" => "1053"
                        "paginaFinal" => "1059"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            57 => array:3 [
              "identificador" => "bib0665"
              "etiqueta" => "58"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical remission of cutaneous squamous cell carcinoma of the auricle with cetuximab and nivolumab"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46; Chen"
                            1 => "A&#46; Nabilah"
                            2 => "P&#46; Boasberg"
                            3 => "S&#46; Allen Ho"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "J Clin Med&#46;"
                        "fecha" => "2018"
                        "volumen" => "7"
                        "paginaInicial" => "10"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            58 => array:3 [
              "identificador" => "bib0670"
              "etiqueta" => "59"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cemiplimab &#40;REGN2810&#41;&#58; A fully human anti-PD-1 monoclonal antibody for patients with unresectable locally advanced or metastatic cutaneous squamous cell carcinoma &#40;CSCC&#41;&#58; Initial safety and efficacy from expansion cohorts &#40;ECs&#41; of phase I study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46;P&#46; Papadopoulos"
                            1 => "T&#46;K&#46; Owonikoko"
                            2 => "M&#46;L&#46; Johnson"
                            3 => "I&#46; Brana"
                            4 => "M&#46; Gil-Martin"
                            5 => "R&#46;P&#46; Perez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol&#46;"
                        "fecha" => "2017"
                        "volumen" => "35"
                        "numero" => "suppl"
                        "paginaInicial" => "195"
                        "itemHostRev" => array:3 [
                          "pii" => "S0735109709034706"
                          "estado" => "S300"
                          "issn" => "07351097"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            59 => array:3 [
              "identificador" => "bib0675"
              "etiqueta" => "60"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Phase 1 study of cemiplimab&#44; a human monoclonal anti-PD-1&#44; in patients with unresectable locally advanced or metastatic cutaneous squamous cell carcinoma &#40;CSCC&#41;&#58; Final efficacy and safety data"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46; Kunle Owonikoko"
                            1 => "K&#46; Papadopoulos"
                            2 => "M&#46; Gil-Martin"
                            3 => "V&#46; Moreno"
                            4 => "A&#46;K&#46; Salama"
                            5 => "E&#46; Calvo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "J Clin Oncol&#46;"
                        "fecha" => "2018"
                        "volumen" => "36"
                        "numero" => "suppl"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            60 => array:3 [
              "identificador" => "bib0680"
              "etiqueta" => "61"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;R&#46; Migden"
                            1 => "D&#46; Rischin"
                            2 => "C&#46;D&#46; Schmults"
                            3 => "A&#46; Guminski"
                            4 => "A&#46; Hauschild"
                            5 => "K&#46;D&#46; Lewis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1805131"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med&#46;"
                        "fecha" => "2018"
                        "volumen" => "379"
                        "paginaInicial" => "341"
                        "paginaFinal" => "351"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29863979"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            61 => array:3 [
              "identificador" => "bib0685"
              "etiqueta" => "62"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidermal growth factor receptor inhibitors for treatment of orbital squamous cell carcinoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46; El-Sawy"
                            1 => "A&#46;L&#46; Sabichi"
                            2 => "J&#46;N&#46; Myers"
                            3 => "M&#46;S&#46; Kies"
                            4 => "W&#46;N&#46; William"
                            5 => "B&#46;S&#46; Glisson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/archophthalmol.2012.2515"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Ophthalmol"
                        "fecha" => "2012"
                        "volumen" => "130"
                        "paginaInicial" => "1608"
                        "paginaFinal" => "1611"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23229707"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "es"
  "url" => "/00017310/0000011000000006/v1_201907020633/S0001731018304976/v1_201907020633/es/main.assets"
  "Apartado" => array:4 [
    "identificador" => "6158"
    "tipo" => "SECCION"
    "es" => array:2 [
      "titulo" => "Revisiones"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "es"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/00017310/0000011000000006/v1_201907020633/S0001731018304976/v1_201907020633/es/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731018304976?idApp=UINPBA000044"
]