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Clinical note
Incidental pathologic extracardiac uptake of 99mTc-tetrofosmin in myocardial perfusion imaging: Importance of patient background evaluation
Captación extracardíaca patológica de 99mTc-tetrofosmin, detectada incidentalmente en un estudio de perfusión miocárdica: importancia de la evaluación de los antecedentes clínicos del paciente
B. González García
Corresponding author
bgg-ist@hotmail.com

Corresponding author.
, A.M. García Vicente, A. Palomar Muñoz, V.M. Poblete García, G.A. Jiménez Londoño, A.M. Soriano Castrejón
Servicio de Medicina Nuclear, Hospital General Universitario de Ciudad Real, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleSup">99m</span>Tc-tetrofosmin single photon emission computed tomography &#40;<span class="elsevierStyleSup">99m</span>Tc-tetrofosmin SPECT&#41; is a well-established&#44; non-invasive imaging technique in the management of angina and myocardial infarction&#44; and has become widely used for diagnosis and assessment of prognosis in patients with known or suspected coronary artery disease&#46; Furthermore it is important to note that <span class="elsevierStyleSup">99m</span>Tc-tetrofosmin is an agent that has been used as oncotropic radiotracer&#44; and is highly concentrated within neoplastic processes of several varieties because of its uptake in mitochondria&#44; being excreted by hepatobiliary system&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In <span class="elsevierStyleSup">99m</span>Tc-tetrofosmin SPECT&#44; although most of the information is obtained from the tomographic slices&#44; the raw projection images should be examined in order to evaluate incidental cardiac or extracardiac findings&#44; and to assess the quality of the study&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">We present a case in which myocardial perfusion imaging &#40;MPI&#41; revealed an unexpected extracardiac activity in posteriomedial region of the right hemithorax&#46; Exhaustive clinical history revision was paramount to a correct evaluation of the finding&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case report</span><p id="par0020" class="elsevierStylePara elsevierViewall">A 71-year-old man&#44; with a history of alcoholism until 5 years ago&#44; without diabetes or hypertension&#44; was referred for a <span class="elsevierStyleSup">99m</span>Tc-tetrofosmin SPECT&#47;CT because of chest pain&#46; Patient was diagnosed of one year ago of squamous cell esophageal carcinoma stage pT2N0M0 and underwent esophagectomy&#46; No chemotherapy or radiotherapy was required&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The day of the MPI&#44; the patient underwent adenosine stress&#44; and subsequently 740<span class="elsevierStyleHsp" style=""></span>MBq <span class="elsevierStyleSup">99m</span>Tc-tetrofosmin was injected intravenously&#46; Thirty minutes after radiotracer injection&#44; a SPECT&#47;CT imaging with a dual head gamma-camera &#40;Infinia Hawkeye&#44; GE&#41; was acquired&#46; The cardiac images showed normal myocardial perfusion but&#44; on the raw projection image&#44; an extracardiac uptake&#44; located in right posterior thorax&#44; near the midline&#44; was noted &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Reconstructed SPECT&#47;CT slices confirmed the activity in the right-posterior mediastinum&#44; with a linear morphology&#44; in correspondence with an elongated mass on CT obtained for attenuation correction purpose &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Additionally&#44; this CT showed massive left pleural effusion&#44; without increased activity of the radiotracer&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">This finding led us to consider on a dilemma&#58; Was related to esophageal cancer recurrence or was a complication due to the received treatment&#63; To clarify the finding interpretation&#44; a revision of clinical and surgical patient background was performed&#46; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT at diagnosis&#44; revealed the primary tumor in upper thoracic esophagus&#44; without lymphadenopathy or distant metastasis &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; Patient underwent surgery &#40;esophagectomy&#44; gastric tube reconstruction and esophagogastric anastomosis&#41;&#44; and one month before the MPI request&#44; another <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT was performed due to suspicion of relapse&#46; The metabolic imaging confirmed locoregional and distant recurrence &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#44; showing relapse in proximal esophagus&#44; while no significant increase in glucose metabolism was evident in the lower 2&#47;3 of the gastroplasty &#40;which showed increased activity in <span class="elsevierStyleSup">99m</span>Tc-tetrofosmin SPECT&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">The comparison between SPECT&#47;CT and PET&#47;CT images &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41; showed that gastroplasty was dilated with liquid content&#44; especially in distal region&#46; Careful re-inspection of SPECT&#47;CT determined that the increased activity corresponded to the content of the gastroplasty&#44; so the findings were due to duodeno-gastro-esophageal reflux&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0040" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleSup">99m</span>Tc-tetrofosmin is cleared from the blood and trapped into mitochondria&#44; reflecting viable myocytes&#46; Furthermore it has shown potential usefulness as tumor-imaging agent&#46; Uptake in tumoral cells depends on the regional blood flow and cell membrane integrity&#44; as well as mitochondrial density&#44; which are increased in these cells&#46; For that reason&#44; many authors have explored the utility of <span class="elsevierStyleSup">99m</span>Tc-tetrofosmin in the diagnosis of various tumors&#44; with a sensitivity and specificity of 82&#46;5&#37; and 100&#37; respectively for esophageal cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">In MPI&#44; during SPECT acquisition&#44; the detector of a gammacamera covers most of the thorax and the abdomen&#46; The evaluation of three-dimensional displays on rotating raw data images has the ability to check for possible artifacts during acquisition and discern abnormalities of the organs or tissues above and below the diaphragm &#40;heart&#44; lungs&#44; mediastinum&#44; liver&#44; spleen and kidneys&#41;&#46; These abnormalities may occur between 0&#46;69 and 41&#46;3&#37; of cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">4&#44;5</span></a><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows a classification of these findings&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">On the other hand&#44; <span class="elsevierStyleSup">99m</span>Tc-tetrofosmin is excreted by the hepatobiliary system&#44; which allows the evaluation of the biliary tract&#44; as well as detection of entero-gastric reflux&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a> It has been reported a prevalence of reflux of 8&#46;3&#37; in MPI&#44; being the second most frequent intra-abdominal abnormality&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">To properly interpret the extracardiac uptake in our study&#44; it was necessary to remember the pharmacokinetics of <span class="elsevierStyleSup">99m</span>Tc-tetrofosmin&#44; and to know the patient&#39;s clinical background&#44; in which two relevant events were reported&#58; first&#44; he was diagnosed of esophageal cancer&#44; with confirmed relapse one month before the MPI&#46; Second&#44; patient underwent esophagectomy&#44; gastroplasty and esophagogastric anastomosis as treatment of his tumor&#46; This surgical approach carries significant morbidity&#44; including late complications such as stricture &#40;up to 52&#37; of patients&#41;&#44; dumping syndrome&#44; delayed gastric emptying&#44; and esophagitis due to acid&#47;bile regurgitation &#40;up to 80&#37; of cases&#41;&#46; In order to perform the differential diagnosis of neoplastic recurrence vs bile reflux&#44; it could be reasonable to recommend additional tests&#44; such as a hepatobiliary scintigraphy to confirm reflux&#44; or an endoscopy or any imaging test to confirm recurrence&#46; Our patient underwent <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT one month before MPI&#44; without evidence of recurrence in the lower 2&#47;3 of the gastroplasty&#46; CT slices showed that gastroplasty was dilated&#44; and had liquid content&#46; A re-inspection of SPECT&#47;CT determined that the increased activity corresponded to the content of the gastroplasty&#44; so we concluded that the findings were due to entero-gastric reflux&#46; Other authors have previously reported bile reflux episodes in <span class="elsevierStyleSup">99m</span>Tc-tetrofosmin SPECT studies performed on patients who had undergone gastroesophageal surgery&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">7&#44;8</span></a> In the present case report&#44; we used additional information from <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT to reach the final diagnosis&#46; This combined assessment has been previously described&#44; but only in the evaluation of tumors&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">9</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Finally&#44; we must remember the reason why the myocardial perfusion imaging was requested&#58; chest pain&#46; The SPECT showed normal myocardial perfusion&#44; so that coronary heart disease was excluded&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">As many as 20&#37; of patients with chest pain underwent catheterization have normal coronary arteries&#46; Of them&#44; up to 50&#37; have pain secondary to digestive disorders&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">10</span></a> When bile reflux presents several typical symptoms associated to chest pain&#44; as heartburn&#44; flatulence and&#47;or nausea&#44; is easily identifiable&#46; However&#44; when it only manifests as chest pain is difficult to establish its etiology&#44; being necessary to rule out coronary disease&#46; Our patient had bile reflux evidenced by <span class="elsevierStyleSup">99m</span>Tc-tetrofosmin SPECT&#47;CT&#44; which had probably led to an irritation of the plasty wall and esophageal remnant&#44; being a potentially treatable cause of chest pain&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Others might be the causes of the patient&#39;s pain&#58; pleuropulmonary disease&#44; with a massive pleural effusion requiring pleurodesis&#44; or psychogenic etiology&#46; The latter was considered the more likely cause by his Oncologist&#59; however&#44; given the MPI findings&#44; it seems obvious that the massive esophagogastric reflux play a role as cause of pain &#40;single or associated with others&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">In conclusion&#44; many benign or malignant abnormalities in the thorax and&#47;or abdomen may be evidenced in a <span class="elsevierStyleSup">99m</span>Tc-tetrofosmin SPECT&#47;CT&#46; Therefore&#44; it is mandatory to review raw data images&#44; report extracardiac findings and investigate the patient&#39;s background&#44; in order to alert clinicians about causes on non-cardiologic chest pain &#40;such bile reflux&#41; or abnormalities that require further investigation&#46;</p></span></span>"
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          "titulo" => "Introduction"
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          "titulo" => "References"
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            0 => "Myocardial perfusion SPECT"
            1 => "Extracardiac findings"
            2 => "Non-cardiac chest pain"
            3 => "<span class="elsevierStyleSup">99m</span>Tc-tetrofosmin"
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          "clase" => "keyword"
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            0 => "SPECT de perfusi&#243;n mioc&#225;rdica"
            1 => "Captaci&#243;n extracard&#237;aca"
            2 => "Dolor tor&#225;cico no cardiol&#243;gico"
            3 => "<span class="elsevierStyleSup">99m</span>Tc-tetrofosmin"
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      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">99m</span>Tc-tetrofosmin single photon emission computed tomography &#40;<span class="elsevierStyleSup">99m</span>Tc-tetrofosmin SPECT&#41; has an important role in the assessment of coronary artery disease&#46; Despite being its main indication&#44; this study does not only evaluate myocardial perfusion&#44; but much more&#46; Moreover&#44; during the SPECT acquisition&#44; the field area covered includes many important organs of the thorax and abdomen&#44; so extracardiac abnormalities can be observed&#46; The correct etiologic diagnosis of them is only possible if we understand how <span class="elsevierStyleSup">99m</span>Tc-tetrofosmin works and make a comprehensive investigation of the clinical history of the patient&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La tomograf&#237;a con <span class="elsevierStyleSup">99m</span>Tc-tetrofosmin &#40;<span class="elsevierStyleSup">99m</span>Tc-tetrofosmin SPECT&#41; desempe&#241;a un papel fundamental en la evaluaci&#243;n de la enfermedad coronaria&#46; A pesar de que esta es su principal indicaci&#243;n&#44; debemos recordar que estos estudios no eval&#250;an &#250;nicamente la perfusi&#243;n mioc&#225;rdica&#44; sino mucho m&#225;s&#46; Adem&#225;s&#44; durante la adquisici&#243;n de la SPECT&#44; el campo incluye gran parte del t&#243;rax y abdomen&#44; por lo que podemos observar enfermedad extracard&#237;aca en las regiones incluidas&#46; Llegar a un correcto diagn&#243;stico etiol&#243;gico de esas alteraciones solo es posible si entendemos c&#243;mo funciona el <span class="elsevierStyleSup">99m</span>Tc-tetrofosmin y realizamos una exhaustiva investigaci&#243;n de los antecedentes e historia cl&#237;nica del paciente&#46;</p></span>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Anterior and lateral raw data of <span class="elsevierStyleSup">99m</span>Tc-tetrofosmin SPECT images at stress show vertical extracardiac linear activity&#44; located in right posterior thorax&#44; near the midline&#46;</p>"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">99m</span>Tc-tetrofosmin SPECT &#40;b&#41; and fused SPECT&#47;CT &#40;c&#41; slices reveal an elongated mass with increased activity in right-posterior mediastinum&#46;</p>"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">18</span>F-FDG PET&#47;TC at diagnosis&#46; Maximum-intensity-projection &#40;a&#41;&#44; axial &#40;b&#41; and sagital &#40;c&#41; PET&#47;CT images show increased uptake in proximal esophagus due to esophageal carcinoma&#44; without lymphadenopathy or distant metastasis&#46;</p>"
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT 1 month before myocardial perfusion study&#46; Maximum-intensity-projection &#40;a&#41; and axial PET&#47;CT images &#40;b&#44;c&#41;&#44; show relapse in proximal esophagus while there is no increased activity in gastric tube &#40;arrow&#41;&#46;</p>"
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">99m</span>Tc-tetrofosmin coronal SPECT&#47;CT &#40;a&#41; and <span class="elsevierStyleSup">18</span>F-FDG coronal PET&#47;CT &#40;b&#41;&#46; The images show increased activity of <span class="elsevierStyleSup">99m</span>Tc-tetrofosmin in SPECT&#47;CT &#40;a&#41; corresponded to the content of the gastroplasty due to reflux&#46; In PET&#47;CT study we can see the dilated gastroplasty&#44; with liquid content&#44; and without hypermetabolism&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Abnormalities above the diaphragm&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Malignant or benign lesions in thyroid&#46;&#8226; Parathyroid lesions &#40;adenoma&#44; hyperplasia&#44; carcinoma&#41;&#46;&#8226; Malignant &#40;primary&#47;metastatic&#41; or benign lesions in the lungs&#46;&#8226; Diffuse and bilateral uptake in the lungs&#46;&#8226; Pleural or pericardial effusion&#46;&#8226; Mediastinal tumor&#46;&#8226; Sarcoidosis&#46;&#8226; Duodenogastroesophageal reflux&#46;&#8226; Hiatus hernia&#46;&#8226; Lyphoma&#46;&#8226; Breast cancer&#46;&#8226; Sternal uptake in anemia and&#47;or hypoxemia&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Abnormalities of the diaphragm&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Elevation or displacement of the diaphragm&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Abnormalities below the diaphragm&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Hepatomegaly&#44; splenomegaly&#46;&#8226; Cirrhosis with ascites&#46;&#8226; Gastric empting abnormalities&#46;&#8226; Duodenogastric biliary reflux&#46;&#8226; Non-visualization of the gallbladder &#40;cholelithiasis&#44; acute cholecystitis&#44; or cholecystectomy&#41;&#46;&#8226; Focal benign &#40;photopenic&#41; or malignant &#40;primary&#47;metastatic&#41; lesions in abdominal organs&#46;&#8226; Vertebral uptake in anemia and&#47;or hypoxemia&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Abnormalities in myocardial perfusion SPECT&#47;CT studies&#46;</p>"
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    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:10 [
            0 => array:3 [
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                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Technetium-99m-1&#44;2-bis &#91;bis&#40;ethoxyethyl&#41; phosphino&#93; ethane&#58; human biodistribution&#44; dosimetry and safety of a new myocardial perfusion imaging agent"
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                        0 => array:2 [
                          "etal" => true
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                            1 => "F&#46;W&#46; Smith"
                            2 => "T&#46; Smith"
                            3 => "H&#46;G&#46; Gemmell"
                            4 => "P&#46; Das Gupta"
                            5 => "D&#46;V&#46; Gvozdanovic"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
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                          ]
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                          "etal" => false
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                            0 => "M&#46;A&#46;M&#46; Ali"
                            1 => "I&#46;M&#46; Koura"
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                          ]
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                          "etal" => true
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                            1 => "B&#46;D&#46; Collier"
                            2 => "R&#46; Shaker"
                            3 => "R&#46;S&#46; Hellman"
                            4 => "S&#46; Smart"
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                          ]
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "W&#46;J&#46; Shih"
                            1 => "P&#46;P&#46; Milan"
                          ]
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