array:22 [
  "pii" => "S2255534X23000683"
  "issn" => "2255534X"
  "doi" => "10.1016/j.rgmxen.2023.02.006"
  "estado" => "S300"
  "fechaPublicacion" => "2023-07-01"
  "aid" => "905"
  "copyrightAnyo" => "2023"
  "documento" => "article"
  "crossmark" => 1
  "subdocumento" => "crp"
  "cita" => "Rev Gastroenterol Mex. 2023;88:296-9"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:1 [
    "total" => 0
  ]
  "itemSiguiente" => array:18 [
    "pii" => "S2255534X23000609"
    "issn" => "2255534X"
    "doi" => "10.1016/j.rgmxen.2023.05.004"
    "estado" => "S300"
    "fechaPublicacion" => "2023-07-01"
    "aid" => "901"
    "copyright" => "Asociación Mexicana de Gastroenterología"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "crp"
    "cita" => "Rev Gastroenterol Mex. 2023;88:299-301"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:11 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Scientific letter</span>"
      "titulo" => "Atypical presentation in adolescence of a gastroesophageal junction adenocarcinoma"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "299"
          "paginaFinal" => "301"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Presentaci&#243;n at&#237;pica en la adolescencia de un adenocarcinoma de la uni&#243;n esofagog&#225;strica"
        ]
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:8 [
          "identificador" => "fig0005"
          "etiqueta" => "Figure 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 2151
              "Ancho" => 2508
              "Tamanyo" => 463148
            ]
          ]
          "detalles" => array:1 [
            0 => array:3 [
              "identificador" => "at0005"
              "detalle" => "Figure "
              "rol" => "short"
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Tumor in the cardia extending into the inferior third of the esophagus&#44; seen by retroflexion during upper endoscopy&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "G&#46; Amaya Villagr&#225;n, K&#46;M&#46; Loya Lazcano, A&#46;A&#46; Baeza Zapata"
          "autores" => array:3 [
            0 => array:2 [
              "nombre" => "G&#46;"
              "apellidos" => "Amaya Villagr&#225;n"
            ]
            1 => array:2 [
              "nombre" => "K&#46;M&#46;"
              "apellidos" => "Loya Lazcano"
            ]
            2 => array:2 [
              "nombre" => "A&#46;A&#46;"
              "apellidos" => "Baeza Zapata"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2255534X23000609?idApp=UINPBA000046"
    "url" => "/2255534X/0000008800000003/v1_202309051335/S2255534X23000609/v1_202309051335/en/main.assets"
  ]
  "itemAnterior" => array:18 [
    "pii" => "S2255534X23000580"
    "issn" => "2255534X"
    "doi" => "10.1016/j.rgmxen.2023.05.002"
    "estado" => "S300"
    "fechaPublicacion" => "2023-07-01"
    "aid" => "899"
    "copyright" => "Asociaci&#243;n Mexicana de Gastroenterolog&#237;a"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "crp"
    "cita" => "Rev Gastroenterol Mex. 2023;88:293-5"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:11 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Scientific letter</span>"
      "titulo" => "Surgical approach to anorectal melanoma&#58; A case report"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "293"
          "paginaFinal" => "295"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Abordaje quir&#250;rgico del melanoma anorrectal&#44; a prop&#243;sito de un caso"
        ]
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:8 [
          "identificador" => "fig0010"
          "etiqueta" => "Figure 2"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr2.jpeg"
              "Alto" => 1005
              "Ancho" => 2675
              "Tamanyo" => 613628
            ]
          ]
          "detalles" => array:1 [
            0 => array:3 [
              "identificador" => "at0010"
              "detalle" => "Figure "
              "rol" => "short"
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A&#46; Mucosa in the anal canal with neoplastic cell infiltration at the junction&#46; B&#46; Connective tissue with melanin pigmentation that extends in a lentiform manner&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "M&#46; Philippe-Ponce, M&#46;A&#46; Vela-Ramos, M&#46;A&#46; Jim&#233;nez-Dur&#225;n, C&#46;Z&#46; D&#237;az-Barrientos, R&#46; Zayas-Borquez"
          "autores" => array:5 [
            0 => array:2 [
              "nombre" => "M&#46;"
              "apellidos" => "Philippe-Ponce"
            ]
            1 => array:2 [
              "nombre" => "M&#46;A&#46;"
              "apellidos" => "Vela-Ramos"
            ]
            2 => array:2 [
              "nombre" => "M&#46;A&#46;"
              "apellidos" => "Jim&#233;nez-Dur&#225;n"
            ]
            3 => array:2 [
              "nombre" => "C&#46;Z&#46;"
              "apellidos" => "D&#237;az-Barrientos"
            ]
            4 => array:2 [
              "nombre" => "R&#46;"
              "apellidos" => "Zayas-Borquez"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2255534X23000580?idApp=UINPBA000046"
    "url" => "/2255534X/0000008800000003/v1_202309051335/S2255534X23000580/v1_202309051335/en/main.assets"
  ]
  "en" => array:15 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Scientific letter</span>"
    "titulo" => "Identified factors for developing recurrent acute pancreatitis and chronic pancreatitis&#58; Genetic etiology should be considered&#46; Report on cases in Mexican children"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "296"
        "paginaFinal" => "299"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "J&#46;A&#46; Macias-Flores, Y&#46; Rivera-Suazo, L&#46;J&#46; Mej&#237;a-Marin"
        "autores" => array:3 [
          0 => array:4 [
            "nombre" => "J&#46;A&#46;"
            "apellidos" => "Macias-Flores"
            "email" => array:1 [
              0 => "dr.maciasflores@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" => "Y&#46;"
            "apellidos" => "Rivera-Suazo"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "L&#46;J&#46;"
            "apellidos" => "Mej&#237;a-Marin"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:3 [
          0 => array:3 [
            "entidad" => "Divisi&#243;n de Gastroenterolog&#237;a&#44; Hospital Infantil de Especialidades de Chihuahua&#44; Chihuahua&#44; Mexico"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Divisi&#243;n de Gastroenterolog&#237;a y Nutrici&#243;n Pedi&#225;trica&#44; Star M&#233;dica Hospital Infantil Privado&#44; Mexico City&#44; Mexico"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Divisi&#243;n de Gen&#233;tica Humana&#44; Centro Estatal de Cancerolog&#237;a&#44; Chihuahua&#44; Mexico"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46; Hospital Infantil de Especialidades de Chihuahua&#44; Av&#46; Carlos Pacheco&#44; s&#47;n&#44; Chihuahua&#44; Mexico&#46; Tel&#46;&#58; 4332900&#59; Ext&#46;&#58; 22941&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Factores identificados para desarrollar pancreatitis aguda recurrente y pancreatitis cr&#243;nica&#58; debemos considerar la etiolog&#237;a gen&#233;tica&#46; Reporte de casos en ni&#241;os mexicanos"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1717
            "Ancho" => 2925
            "Tamanyo" => 235902
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0005"
            "detalle" => "Figure "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The relatives with manifestations of type I diabetes mellitus and pancreatitis are described&#44; as well as asymptomatic relatives&#46; The patient presents with torpid progression by being a carrier&#44; not only of the duplication in the <span class="elsevierStyleItalic">PRSS1</span> gene&#44; but also of a heterozygous variant in the <span class="elsevierStyleItalic">CFTR</span> gene&#44; thus a torpid expression and progression is expected&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Cases of recurrent acute pancreatitis &#40;RAP&#41; and chronic pancreatitis &#40;CP&#41; in children have increased in recent years&#46; RAP is characterized by two or more documented events of acute pancreatitis &#40;AP&#41; and occurs in 10-30&#37; of cases of AP&#46; CP is the end stage of progressive inflammation that manifests as fibrosis of the pancreatic parenchyma that eventually leads to exocrine and&#47;or endocrine dysfunction&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In children&#44; there is usually more than one identified factor that contributes to its development and they are related to a broad range of etiologies &#40;genetic&#44; anatomic&#44; obstructive&#44; pharmacotoxic&#44; traumatic&#44; metabolic &#91;inborn errors of metabolism&#93;&#44; systemic&#44; infectious&#44; autoimmune&#44; and idiopathic&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Said conditions are related to morbidities&#44; emergency room admissions&#44; and hospitalizations&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">We describe herein 6 patients with RAP and 5 with CP&#44; in whom the identified risk factors in the development of RAP and CP&#44; proposed by the INSPPIRE group&#44;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a> were studied&#46; Massive sequencing was carried out using the Illumina&#174; platform&#46; The characteristics of the RAP and CP cases are described in <a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1 and 2</a>&#44; respectively&#46; The risk factors for developing both RAP and CP are similar and genetic causes have been identified in &#62; 50&#37; of the cases of RAP and in &#8764;75&#37; of the cases of CP&#44; with 17&#37; of cases having more than one pathogenic variant&#44; according to the INSPPIRE report&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;5</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The median age at the time of diagnosis was 8 years &#40;interquartile range &#91;IQR&#93; 5-12&#41;&#44; the median number of emergency room visits prior to diagnosis was 3 &#40;IQR 2-5&#41;&#44; and the median number of hospitalizations in the past year was 2 &#40;IQR 0-2&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">In a recent study on 479 children&#44; demographic variables&#44; risk factors&#44; and treatment in RAP and CP were evaluated&#44; and genetic variants were identified as the dominant risk factor&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> In our report&#44; we documented a genetic variant in 45&#46;4&#37; of cases&#44; a higher percentage than that reported by Saito et al&#46; &#40;39&#46;1&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> In the study by Vue et al&#46;&#44; in which 33&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#47;91&#41; of the patients were Hispanic&#44; 36&#37; of the 91 cases had at least one mutation&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In a case series on 115 children that included 20 with RAP &#40;17&#37;&#41;&#44; 16 of them underwent genetic testing&#46; In 6 of those patients&#44; one pathogenic variant was found in one of the 4 gene panels &#40;<span class="elsevierStyleItalic">PRSS1</span> &#91;cationic trypsinogen&#93;&#44; <span class="elsevierStyleItalic">SPINK1</span> &#91;serine protease inhibitor Kazal type 1&#93;&#44; <span class="elsevierStyleItalic">CFTR</span> &#91;cystic fibrosis transmembrane conductance regulator&#93;&#44; and <span class="elsevierStyleItalic">CTRC</span> &#91;chymotrypsin C&#93;&#41;&#59; <span class="elsevierStyleItalic">CFTR</span> was the most frequently found genetic variant&#44; followed by <span class="elsevierStyleItalic">PRSS1</span> and <span class="elsevierStyleItalic">SPINK1&#46;</span><a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> The difference from our findings was likely due to our small sample size and the higher prevalence of the <span class="elsevierStyleItalic">CFTR</span> mutation that is found in the White population&#46; In the Mexican population&#44; in a total of 55 patients &#40;65&#46;5&#37; with AP&#59; 34&#46;5&#37; with RAP&#41;&#44; S&#225;nchez-Ram&#237;rez et al&#46; identified a frequency of 1&#46;8&#37; for the pathogenic variant in the <span class="elsevierStyleItalic">CFTR</span> gene&#44; corresponding to one patient in the RAP subgroup&#46; However&#44; none of the children were studied for variants in the <span class="elsevierStyleItalic">PRSS1</span> or <span class="elsevierStyleItalic">SPINK1</span> genes&#44; and no cases of CP were included&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Four of our 5 patients with CP presented with heterozygous pathogenic variants in the <span class="elsevierStyleItalic">PRSS1</span> gene &#40;complete duplication of the coding region&#41; and one patient presented with 2 heterozygous pathogenic variants &#40;<span class="elsevierStyleItalic">CFTR</span> &#91;p&#46;Phe508del&#93; and <span class="elsevierStyleItalic">PRSS1</span> &#91;complete duplication of the coding region&#93;&#41;&#46; In that sense&#44; the presence of certain pathogenic variants in the <span class="elsevierStyleItalic">PRSS1</span> gene &#40;p&#46;N29I or R122H&#41; has been related to a greater probability of a progressive disease that evolves into CP&#44; and later&#44; even into pancreatic cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a><a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> illustrates how a variant can be inherited in a family and expressed in distinct forms&#46; Strikingly&#44; all the patients analyzed presented with the same pathogenic variant in the <span class="elsevierStyleItalic">PRSS1</span> gene&#44; leading us to suspect they could have had a common ancestor&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">A positive family history for pancreatitis has been described to be more frequent in patients with pathogenic variants and 30&#37; of patients with RAP or CP have a family history of pancreatitis&#44; similar to our finding of 27&#46;2&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;7</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">We found 2 patients &#40;RAP subgroup&#41; with an obstructive factor&#46; In a study on adult patients with RAP&#44; Saraswat et al&#46; reported that 75&#37; of the microscopic studies of the gallbladder revealed cholesterol crystals and calcium bilirubinate granules associated with microlithiasis&#46; Thirty months after microlithiasis treatment &#40;ursodeoxycholic acid&#44; sphincterotomy&#44; or cholecystectomy&#41;&#44; the patients were asymptomatic&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In pediatrics&#44; the metabolic risk factors for RAP and CP are related to diabetic ketoacidosis&#44; hypertriglyceridemia&#44; hypercalcemia associated with hyperparathyroidism&#44; and less frequently&#44; to inborn errors of metabolism&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> We found that 2 patients with RAP presented with a metabolic factor&#58; one patient had hypertriglyceridemia &#40;levels &#62; 1&#44;000<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#41;&#46; Serum levels &#62; 1&#44;000<span class="elsevierStyleHsp" style=""></span>mg&#47;dl are an absolute risk factor for the development of AP&#46; One of our patients presented with parathyroid adenoma&#44; which is the most common cause of hypercalcemia &#40;&#62; 10&#46;7<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Patients with a metabolic factor had a later mean age at presentation than the patients with RAP and no metabolic factor &#40;10&#46;5 vs&#46; 7&#46;16 years&#41;&#44; a finding similar to that reported by Husain et al&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Pediatric patients with symptoms of pancreatitis do not always undergo an extensive diagnostic evaluation&#46; Therefore&#44; we must promote a proactive position from the time of RAP diagnosis&#44; emphasizing and prioritizing genetic testing&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">We recommend that pediatric patients with no identifiable etiology of pancreatitis undergo genetic counseling&#44; given that early typing of the risk factors could improve the therapeutic focus&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;13</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Ethical considerations</span><p id="par0070" class="elsevierStylePara elsevierViewall">The authors declare they reviewed the clinical records to collect the data and that they were handled confidentially so that no patient could be individually identified&#46; Neither authorization by the Ethics Committee nor signed statements of informed consent were required&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Financial disclosure</span><p id="par0075" class="elsevierStylePara elsevierViewall">No specific grants were received from public sector agencies&#44; the business sector&#44; or non-profit organizations in relation to this article&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflict of interest</span><p id="par0080" class="elsevierStylePara elsevierViewall">The authors declare that there is no conflict of interest&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:4 [
        0 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Ethical considerations"
        ]
        1 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Financial disclosure"
        ]
        2 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Conflict of interest"
        ]
        3 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Please cite this article as&#58; Macias-Flores JA&#44; Rivera-Suazo Y&#44; Mej&#237;a-Marin LJ&#46; Factores identificados para desarrollar pancreatitis aguda recurrente y pancreatitis cr&#243;nica&#58; debemos considerar la etiolog&#237;a gen&#233;tica&#46; Reporte de casos en ni&#241;os mexicanos&#46; Rev Gastroenterol M&#233;x&#46; 2023&#59;88&#58;296&#8211;299&#46;</p>"
      ]
    ]
    "multimedia" => array:3 [
      0 => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1717
            "Ancho" => 2925
            "Tamanyo" => 235902
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0005"
            "detalle" => "Figure "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The relatives with manifestations of type I diabetes mellitus and pancreatitis are described&#44; as well as asymptomatic relatives&#46; The patient presents with torpid progression by being a carrier&#44; not only of the duplication in the <span class="elsevierStyleItalic">PRSS1</span> gene&#44; but also of a heterozygous variant in the <span class="elsevierStyleItalic">CFTR</span> gene&#44; thus a torpid expression and progression is expected&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0010"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">BMI&#58; body mass index expressed in percentiles by the Centers for Disease Control and Prevention&#59; F&#58; female&#59; M&#58; male&#59; <span class="elsevierStyleItalic">PRSS1</span>&#58; cationic trypsinogen&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">BMI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Identified factor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Age &#40;years&#41; at onset of symptoms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Age &#40;years&#41; at diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Family history&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><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">1&#44; M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Genetic &#40;<span class="elsevierStyleItalic">PRSS1</span> pathogenic variant<span class="elsevierStyleItalic">&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pancreatitis &#40;brother&#41;&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">2&#44; F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Obstructive &#40;cholelithiasis&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&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">3&#44; F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Metabolic &#40;hypertriglyceridemia&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&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">4&#44; M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idiopathic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&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">5&#44; F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">92&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Obstructive &#40;microlithiasis&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&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">6&#44; M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Metabolic &#40;hypercalcemia&#47;primary hyperparathyroidism&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pancreatitis &#40;maternal aunt and grandmother&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3261031.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Clinical characteristics&#44; identified factors&#44; and radiologic findings in the recurrent acute pancreatitis group&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0015"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">BMI&#58; body mass index expressed in percentiles of Centers for Disease Control and Prevention&#59; <span class="elsevierStyleItalic">CFTR</span>&#58; cystic fibrosis transmembrane conductance regulator&#59; EPIn&#58; endocrine pancreatic insufficiency&#59; EPIx&#58; exocrine pancreatic insufficiency&#59; F&#58; female&#59; M&#58; male&#59; <span class="elsevierStyleItalic">PRSS1</span>&#58; cationic trypsinogen&#59; RAP&#58; recurrent acute pancreatitis&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">BMI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Identified factor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Age &#40;years&#41;&#44; at symptom onset&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Age &#40;years&#41; at diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Family history&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Imaging findings&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">EPIx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">EPIn&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><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">1&#44; M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Genetic &#40;<span class="elsevierStyleItalic">PRSS1</span> pathogenic variant&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RAP &#40;brother&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Calcification&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&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">2&#44; M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Genetic &#40;<span class="elsevierStyleItalic">CFTR<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>PRSS1</span> pathogenic variants&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Type I diabetes mellitus &#40;father and maternal grandmother&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Main pancreatic duct dilation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&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">3&#44; F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Genetic &#40;<span class="elsevierStyleItalic">PRSS1</span> pathogenic variant&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Calcification and fibrosis in biopsy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&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">4&#44; F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Genetic &#40;<span class="elsevierStyleItalic">PRSS1</span> pathogenic variant<span class="elsevierStyleItalic">&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Calcification&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&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">5&#44; M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">94&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idiopathic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Calcification&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3261032.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Clinical characteristics&#44; identified factors&#44; and radiologic findings in the chronic pancreatitis group&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:14 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Genetic mutations in pediatric pancreatitis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "P&#46;M&#46; Vue"
                            1 => "K&#46; McFann"
                            2 => "M&#46;R&#46; Narkewicz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/MPA.0000000000000589"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pancreas"
                        "fecha" => "2016"
                        "volumen" => "45"
                        "paginaInicial" => "992"
                        "paginaFinal" => "996"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26692446"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Recurrent pancreatitis in children&#58; past&#44; present&#44; and future"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "K&#46;M&#46; Ellery"
                            1 => "A&#46; Uc"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/MPG.0000000000002619"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Pediatr Gastroenterol Nutr"
                        "fecha" => "2020"
                        "volumen" => "70"
                        "paginaInicial" => "413"
                        "paginaFinal" => "416"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31899736"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pancreatitis in children"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46; Uc"
                            1 => "S&#46;Z&#46; Husain"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/j.gastro.2018.12.043"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gastroenterology"
                        "fecha" => "2019"
                        "volumen" => "156"
                        "paginaInicial" => "1969"
                        "paginaFinal" => "1978"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30716320"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nationwide trends in acute and chronic pancreatitis among privately insured children and non-elderly adults in the United States&#44; 2007-2014"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "Z&#46;M&#46; Sellers"
                            1 => "D&#46; MacIsaac"
                            2 => "H&#46; Yu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/j.gastro.2018.04.013"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gastroenterology"
                        "fecha" => "2018"
                        "volumen" => "155"
                        "paginaInicial" => "469"
                        "paginaFinal" => "478"
                        "itemHostRev" => array:3 [
                          "pii" => "S1807593222032057"
                          "estado" => "S300"
                          "issn" => "18075932"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk factors associated with pediatric acute recurrent and chronic pancreatitis&#58; lessons from INSPPIRE"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "S&#46; Kumar"
                            1 => "C&#46;Y&#46; Ooi"
                            2 => "S&#46; Werlin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jamapediatrics.2015.4955"
                      "Revista" => array:5 [
                        "tituloSerie" => "JAMA Pediatr"
                        "fecha" => "2016"
                        "volumen" => "170"
                        "paginaInicial" => "562"
                        "paginaFinal" => "569"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk factors for rapid progression from acute recurrent to chronic pancreatitis in children&#58; report from INSPPIRE"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "Q&#46;Y&#46; Liu"
                            1 => "M&#46; Abu-El-Haija"
                            2 => "S&#46;Z&#46; Husain"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/MPG.0000000000002405"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Pediatr Gastroenterol Nutr"
                        "fecha" => "2019"
                        "volumen" => "69"
                        "paginaInicial" => "206"
                        "paginaFinal" => "211"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31136562"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical and practice variations in pediatric acute recurrent or chronic pancreatitis&#58; report from the INSPPIRE study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "C&#46;R&#46; Dike"
                            1 => "B&#46; Zimmerman"
                            2 => "Y&#46; Zheng"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/MPG.0000000000002661"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Pediatr Gastroenterol Nutr"
                        "fecha" => "2020"
                        "volumen" => "71"
                        "paginaInicial" => "112"
                        "paginaFinal" => "118"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32079978"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Genetic analysis of Japanese children with acute recurrent and chronic pancreatitis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "N&#46; Saito"
                            1 => "M&#46; Suzuki"
                            2 => "Y&#46; Sakurai"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/MPG.0000000000001320"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Pediatr Gastroenterol Nutr"
                        "fecha" => "2016"
                        "volumen" => "63"
                        "paginaInicial" => "431"
                        "paginaFinal" => "436"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27409067"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S1807593222032033"
                          "estado" => "S300"
                          "issn" => "18075932"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Rapid progression of acute pancreatitis to acute recurrent pancreatitis in children"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "K&#46;F&#46; Sweeny"
                            1 => "T&#46;K&#46; Lin"
                            2 => "J&#46;D&#46; Nathan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/MPG.0000000000002145"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Pediatr Gastroenterol Nutr"
                        "fecha" => "2019"
                        "volumen" => "68"
                        "paginaInicial" => "104"
                        "paginaFinal" => "109"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30234758"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Acute and recurrent pancreatitis in children&#58; etiological factors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "C&#46;A&#46; S&#225;nchez-Ram&#237;rez"
                            1 => "A&#46; Larrosa-Haro"
                            2 => "S&#46; Flores-Mart&#237;nez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1651-2227.2007.00225.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Acta Paediatr"
                        "fecha" => "2007"
                        "volumen" => "96"
                        "paginaInicial" => "534"
                        "paginaFinal" => "537"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17306005"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Early-onset acute recurrent and chronic pancreatitis is associated with PRSS1 or CTRC gene mutations"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "M&#46;J&#46; Giefer"
                            1 => "M&#46;E&#46; Lowe"
                            2 => "S&#46;L&#46; Werlin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jpeds.2017.03.063"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Pediatr"
                        "fecha" => "2017"
                        "volumen" => "186"
                        "paginaInicial" => "95"
                        "paginaFinal" => "100"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28502372"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Biliary microlithiasis in patients with idiopathic acute pancreatitis and unexplained biliary pain&#58; response to therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "V&#46;A&#46; Saraswat"
                            1 => "B&#46;C&#46; Sharma"
                            2 => "D&#46;K&#46; Agarwal"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1440-1746.2004.03462.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Gastroenterol Hepatol"
                        "fecha" => "2004"
                        "volumen" => "19"
                        "paginaInicial" => "1206"
                        "paginaFinal" => "1211"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15377301"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Causal evaluation of acute recurrent and chronic pancreatitis in children&#58; consensus from the INSPPIRE group"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "C&#46;E&#46; Gariepy"
                            1 => "M&#46;B&#46; Heyman"
                            2 => "M&#46;E&#46; Lowe"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/MPG.0000000000001446"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Pediatr Gastroenterol Nutr"
                        "fecha" => "2017"
                        "volumen" => "64"
                        "paginaInicial" => "95"
                        "paginaFinal" => "103"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27782962"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S1807593222031970"
                          "estado" => "S300"
                          "issn" => "18075932"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Toxic-metabolic risk factors in pediatric pancreatitis&#58; recommendations for diagnosis&#44; management&#44; and future research"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "S&#46;Z&#46; Husain"
                            1 => "V&#46; Morinville"
                            2 => "J&#46; Pohl"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/MPG.0000000000001035"
                      "Revista" => array:5 [
                        "tituloSerie" => "J Pediatr Gastroenterol Nutr"
                        "fecha" => "2016"
                        "volumen" => "62"
                        "paginaInicial" => "609"
                        "paginaFinal" => "617"
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/2255534X/0000008800000003/v1_202309051335/S2255534X23000683/v1_202309051335/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "23969"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Scientific Letters"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/2255534X/0000008800000003/v1_202309051335/S2255534X23000683/v1_202309051335/en/main.pdf?idApp=UINPBA000046&text.app=https://www.revistagastroenterologiamexico.org/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2255534X23000683?idApp=UINPBA000046"
]
Share
Journal Information
Vol. 88. Issue 3.
Pages 296-299 (July - September 2023)
Share
Share
Download PDF
More article options
Visits
2250
Vol. 88. Issue 3.
Pages 296-299 (July - September 2023)
Scientific letter
Full text access
Identified factors for developing recurrent acute pancreatitis and chronic pancreatitis: Genetic etiology should be considered. Report on cases in Mexican children
Factores identificados para desarrollar pancreatitis aguda recurrente y pancreatitis crónica: debemos considerar la etiología genética. Reporte de casos en niños mexicanos
Visits
2250
J.A. Macias-Floresa,
Corresponding author
dr.maciasflores@hotmail.com

Corresponding author. Hospital Infantil de Especialidades de Chihuahua, Av. Carlos Pacheco, s/n, Chihuahua, Mexico. Tel.: 4332900; Ext.: 22941.
, Y. Rivera-Suazob, L.J. Mejía-Marinc
a División de Gastroenterología, Hospital Infantil de Especialidades de Chihuahua, Chihuahua, Mexico
b División de Gastroenterología y Nutrición Pediátrica, Star Médica Hospital Infantil Privado, Mexico City, Mexico
c División de Genética Humana, Centro Estatal de Cancerología, Chihuahua, Mexico
This item has received
Article information
Full Text
Bibliography
Download PDF
Statistics
Figures (1)
Tables (2)
Table 1. Clinical characteristics, identified factors, and radiologic findings in the recurrent acute pancreatitis group.
Table 2. Clinical characteristics, identified factors, and radiologic findings in the chronic pancreatitis group.
Show moreShow less
Full Text

Cases of recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) in children have increased in recent years. RAP is characterized by two or more documented events of acute pancreatitis (AP) and occurs in 10-30% of cases of AP. CP is the end stage of progressive inflammation that manifests as fibrosis of the pancreatic parenchyma that eventually leads to exocrine and/or endocrine dysfunction.1,2

In children, there is usually more than one identified factor that contributes to its development and they are related to a broad range of etiologies (genetic, anatomic, obstructive, pharmacotoxic, traumatic, metabolic [inborn errors of metabolism], systemic, infectious, autoimmune, and idiopathic).3 Said conditions are related to morbidities, emergency room admissions, and hospitalizations.4

We describe herein 6 patients with RAP and 5 with CP, in whom the identified risk factors in the development of RAP and CP, proposed by the INSPPIRE group,5,6 were studied. Massive sequencing was carried out using the Illumina® platform. The characteristics of the RAP and CP cases are described in Tables 1 and 2, respectively. The risk factors for developing both RAP and CP are similar and genetic causes have been identified in > 50% of the cases of RAP and in ∼75% of the cases of CP, with 17% of cases having more than one pathogenic variant, according to the INSPPIRE report.3,5

Table 1.

Clinical characteristics, identified factors, and radiologic findings in the recurrent acute pancreatitis group.

Patient  BMI  Identified factor  Age (years) at onset of symptoms  Age (years) at diagnosis  Family history 
1, M  97  Genetic (PRSS1 pathogenic variant)  Pancreatitis (brother) 
2, F  35  Obstructive (cholelithiasis)  – 
3, F  52  Metabolic (hypertriglyceridemia)  – 
4, M  26  Idiopathic  12  – 
5, F  92  Obstructive (microlithiasis)  – 
6, M  40  Metabolic (hypercalcemia/primary hyperparathyroidism)  13  13  Pancreatitis (maternal aunt and grandmother) 

BMI: body mass index expressed in percentiles by the Centers for Disease Control and Prevention; F: female; M: male; PRSS1: cationic trypsinogen.

Table 2.

Clinical characteristics, identified factors, and radiologic findings in the chronic pancreatitis group.

Patient  BMI  Identified factor  Age (years), at symptom onset  Age (years) at diagnosis  Family history  Imaging findings  EPIx  EPIn 
1, M  Genetic (PRSS1 pathogenic variant)  12  12  RAP (brother)  Calcification  – 
2, M  Genetic (CFTR+PRSS1 pathogenic variants)  Type I diabetes mellitus (father and maternal grandmother)  Main pancreatic duct dilation  – 
3, F  10  Genetic (PRSS1 pathogenic variant)  10  11  –  Calcification and fibrosis in biopsy  – 
4, F  Genetic (PRSS1 pathogenic variant)  –  Calcification  – 
5, M  94  Idiopathic  12  13  –  Calcification  – 

BMI: body mass index expressed in percentiles of Centers for Disease Control and Prevention; CFTR: cystic fibrosis transmembrane conductance regulator; EPIn: endocrine pancreatic insufficiency; EPIx: exocrine pancreatic insufficiency; F: female; M: male; PRSS1: cationic trypsinogen; RAP: recurrent acute pancreatitis.

The median age at the time of diagnosis was 8 years (interquartile range [IQR] 5-12), the median number of emergency room visits prior to diagnosis was 3 (IQR 2-5), and the median number of hospitalizations in the past year was 2 (IQR 0-2).

In a recent study on 479 children, demographic variables, risk factors, and treatment in RAP and CP were evaluated, and genetic variants were identified as the dominant risk factor.7 In our report, we documented a genetic variant in 45.4% of cases, a higher percentage than that reported by Saito et al. (39.1%).8 In the study by Vue et al., in which 33% (n=30/91) of the patients were Hispanic, 36% of the 91 cases had at least one mutation.1

In a case series on 115 children that included 20 with RAP (17%), 16 of them underwent genetic testing. In 6 of those patients, one pathogenic variant was found in one of the 4 gene panels (PRSS1 [cationic trypsinogen], SPINK1 [serine protease inhibitor Kazal type 1], CFTR [cystic fibrosis transmembrane conductance regulator], and CTRC [chymotrypsin C]); CFTR was the most frequently found genetic variant, followed by PRSS1 and SPINK1.9 The difference from our findings was likely due to our small sample size and the higher prevalence of the CFTR mutation that is found in the White population. In the Mexican population, in a total of 55 patients (65.5% with AP; 34.5% with RAP), Sánchez-Ramírez et al. identified a frequency of 1.8% for the pathogenic variant in the CFTR gene, corresponding to one patient in the RAP subgroup. However, none of the children were studied for variants in the PRSS1 or SPINK1 genes, and no cases of CP were included.10

Four of our 5 patients with CP presented with heterozygous pathogenic variants in the PRSS1 gene (complete duplication of the coding region) and one patient presented with 2 heterozygous pathogenic variants (CFTR [p.Phe508del] and PRSS1 [complete duplication of the coding region]). In that sense, the presence of certain pathogenic variants in the PRSS1 gene (p.N29I or R122H) has been related to a greater probability of a progressive disease that evolves into CP, and later, even into pancreatic cancer.11Fig. 1 illustrates how a variant can be inherited in a family and expressed in distinct forms. Strikingly, all the patients analyzed presented with the same pathogenic variant in the PRSS1 gene, leading us to suspect they could have had a common ancestor.

Figure 1.

The relatives with manifestations of type I diabetes mellitus and pancreatitis are described, as well as asymptomatic relatives. The patient presents with torpid progression by being a carrier, not only of the duplication in the PRSS1 gene, but also of a heterozygous variant in the CFTR gene, thus a torpid expression and progression is expected.

(0.22MB).

A positive family history for pancreatitis has been described to be more frequent in patients with pathogenic variants and 30% of patients with RAP or CP have a family history of pancreatitis, similar to our finding of 27.2%.1,7

We found 2 patients (RAP subgroup) with an obstructive factor. In a study on adult patients with RAP, Saraswat et al. reported that 75% of the microscopic studies of the gallbladder revealed cholesterol crystals and calcium bilirubinate granules associated with microlithiasis. Thirty months after microlithiasis treatment (ursodeoxycholic acid, sphincterotomy, or cholecystectomy), the patients were asymptomatic.12

In pediatrics, the metabolic risk factors for RAP and CP are related to diabetic ketoacidosis, hypertriglyceridemia, hypercalcemia associated with hyperparathyroidism, and less frequently, to inborn errors of metabolism.13 We found that 2 patients with RAP presented with a metabolic factor: one patient had hypertriglyceridemia (levels > 1,000mg/dl). Serum levels > 1,000mg/dl are an absolute risk factor for the development of AP. One of our patients presented with parathyroid adenoma, which is the most common cause of hypercalcemia (> 10.7mg/dl).14

Patients with a metabolic factor had a later mean age at presentation than the patients with RAP and no metabolic factor (10.5 vs. 7.16 years), a finding similar to that reported by Husain et al.14

Pediatric patients with symptoms of pancreatitis do not always undergo an extensive diagnostic evaluation. Therefore, we must promote a proactive position from the time of RAP diagnosis, emphasizing and prioritizing genetic testing.

We recommend that pediatric patients with no identifiable etiology of pancreatitis undergo genetic counseling, given that early typing of the risk factors could improve the therapeutic focus.9,13

Ethical considerations

The authors declare they reviewed the clinical records to collect the data and that they were handled confidentially so that no patient could be individually identified. Neither authorization by the Ethics Committee nor signed statements of informed consent were required.

Financial disclosure

No specific grants were received from public sector agencies, the business sector, or non-profit organizations in relation to this article.

Conflict of interest

The authors declare that there is no conflict of interest.

References
[1]
P.M. Vue, K. McFann, M.R. Narkewicz.
Genetic mutations in pediatric pancreatitis.
Pancreas, 45 (2016), pp. 992-996
[2]
K.M. Ellery, A. Uc.
Recurrent pancreatitis in children: past, present, and future.
J Pediatr Gastroenterol Nutr, 70 (2020), pp. 413-416
[3]
A. Uc, S.Z. Husain.
Pancreatitis in children.
Gastroenterology, 156 (2019), pp. 1969-1978
[4]
Z.M. Sellers, D. MacIsaac, H. Yu, et al.
Nationwide trends in acute and chronic pancreatitis among privately insured children and non-elderly adults in the United States, 2007-2014.
Gastroenterology, 155 (2018), pp. 469-478
[5]
S. Kumar, C.Y. Ooi, S. Werlin, et al.
Risk factors associated with pediatric acute recurrent and chronic pancreatitis: lessons from INSPPIRE.
JAMA Pediatr, 170 (2016), pp. 562-569
[6]
Q.Y. Liu, M. Abu-El-Haija, S.Z. Husain, et al.
Risk factors for rapid progression from acute recurrent to chronic pancreatitis in children: report from INSPPIRE.
J Pediatr Gastroenterol Nutr, 69 (2019), pp. 206-211
[7]
C.R. Dike, B. Zimmerman, Y. Zheng, et al.
Clinical and practice variations in pediatric acute recurrent or chronic pancreatitis: report from the INSPPIRE study.
J Pediatr Gastroenterol Nutr, 71 (2020), pp. 112-118
[8]
N. Saito, M. Suzuki, Y. Sakurai, et al.
Genetic analysis of Japanese children with acute recurrent and chronic pancreatitis.
J Pediatr Gastroenterol Nutr, 63 (2016), pp. 431-436
[9]
K.F. Sweeny, T.K. Lin, J.D. Nathan, et al.
Rapid progression of acute pancreatitis to acute recurrent pancreatitis in children.
J Pediatr Gastroenterol Nutr, 68 (2019), pp. 104-109
[10]
C.A. Sánchez-Ramírez, A. Larrosa-Haro, S. Flores-Martínez, et al.
Acute and recurrent pancreatitis in children: etiological factors.
Acta Paediatr, 96 (2007), pp. 534-537
[11]
M.J. Giefer, M.E. Lowe, S.L. Werlin, et al.
Early-onset acute recurrent and chronic pancreatitis is associated with PRSS1 or CTRC gene mutations.
J Pediatr, 186 (2017), pp. 95-100
[12]
V.A. Saraswat, B.C. Sharma, D.K. Agarwal, et al.
Biliary microlithiasis in patients with idiopathic acute pancreatitis and unexplained biliary pain: response to therapy.
J Gastroenterol Hepatol, 19 (2004), pp. 1206-1211
[13]
C.E. Gariepy, M.B. Heyman, M.E. Lowe, et al.
Causal evaluation of acute recurrent and chronic pancreatitis in children: consensus from the INSPPIRE group.
J Pediatr Gastroenterol Nutr, 64 (2017), pp. 95-103
[14]
S.Z. Husain, V. Morinville, J. Pohl, et al.
Toxic-metabolic risk factors in pediatric pancreatitis: recommendations for diagnosis, management, and future research.
J Pediatr Gastroenterol Nutr, 62 (2016), pp. 609-617

Please cite this article as: Macias-Flores JA, Rivera-Suazo Y, Mejía-Marin LJ. Factores identificados para desarrollar pancreatitis aguda recurrente y pancreatitis crónica: debemos considerar la etiología genética. Reporte de casos en niños mexicanos. Rev Gastroenterol Méx. 2023;88:296–299.

Download PDF
Idiomas
Revista de Gastroenterología de México
Article options
Tools
es en
Política de cookies Cookies policy
Utilizamos cookies propias y de terceros para mejorar nuestros servicios y mostrarle publicidad relacionada con sus preferencias mediante el análisis de sus hábitos de navegación. Si continua navegando, consideramos que acepta su uso. Puede cambiar la configuración u obtener más información aquí. To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here.