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Head and neck cancer screening in patients eligible for liver transplantation
Cribado de cáncer de cabeza y cuello en pacientes candidatos a trasplante hepático
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The most frequent causes are cirrhosis secondary to chronic viral hepatitis and secondary to alcohol abuse, which together constitute 70% of current indications.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The absolute contraindications for liver transplant include uncontrolled malignant tumours.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Head and neck carcinomas (HNC) are the sixth most common cancers worldwide and have a high mortality rate. Within these cancers, the larynx followed by the oral cavity are the most common subsites in our country and the predominant histological type is the epidermoid strain.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">A significant percentage of HNCs in our country are associated with excessive smoking and alcohol consumption. The relative risk for smoking in the development of a HNC ranges from 1.5 to 10 depending on the site, and for alcohol, in the case of oropharyngeal carcinomas, it is 8.8 in heavy drinkers (more than 30 alcoholic drinks per week). On the other hand, there is a multiplier effect in cases of simultaneous tobacco and alcohol use, with an odds ratio of 37.7 for heavy smokers (more than one pack per day for more than 20 years) and high alcohol intake.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Previous studies show that more than 50% of liver transplant candidates are active smokers and/or drinkers or have had a significant history as such.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a> Hence, many pre-liver transplant protocols include a full examination of the head and neck prior to transplantation.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> This examination should include visual examination and palpation of the oral cavity, neck palpation, and endoscopy of the nostrils, pharynx and larynx. This examination is to rule out the presence of a synchronous malignant tumour and is relatively simple, non-invasive and inexpensive.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Since the beginning of the Liver Transplant Programme at our hospital in 1990, a complete examination of the head and neck area was included in the pre-transplant protocol. The aim of our study was to evaluate the usefulness of pre-transplant ENT assessment to discount the presence of malignant head and neck tumours in patients who are candidates for liver transplantation. Chest x-rays are routinely performed to assess lung anatomy. The gastro-intestinal department is in charge of ruling out oesophageal disorders beforehand.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><p id="par0035" class="elsevierStylePara elsevierViewall">A retrospective descriptive epidemiological study was conducted on all the patients who were candidates for liver transplants sent by the gastro-intestinal department for pre-transplant assessment to the Marqués de Valdecilla University Hospital, a referral centre for liver transplants in a health area of 570,000 inhabitants in northern Spain. The study period was from 1 January 2011 to 31 March 2017.</p><p id="par0040" class="elsevierStylePara elsevierViewall">In addition to taking a clinical history to discount symptoms suspicious of head and neck carcinoma, all patients underwent an examination that included: examination of the skin of the head and neck, palpation of the neck, examination of the oral cavity with palpation of suspicious areas and nasofibroscopy of nostrils, pharynx and larynx. In cases of high suspicion of a malignant tumour, the study was completed with imaging tests (usually CT, and occasionally MRI or PET-CT) and biopsy of the suspicious areas.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0045" class="elsevierStylePara elsevierViewall">A total of 141 liver transplant candidates were assessed by the ENT department to rule out malignant or infectious disease during the study period. Of these patients, 96 cases (68%) were of alcoholic origin, 26 (18%) were due to cirrhosis secondary to the hepatitis C virus, and 19 cases were due to other causes (14%). Of these, 113 (80%) were smokers and 28 (20%) were non-smokers. In 2 patients (1.3%) who were asymptomatic from an ENT perspective, a head and neck tumour was found, which was biopsied with a diagnosis of epidermoid carcinoma. Both had a history of high alcohol intake and smoking. Both patients were treated by concomitant chemoradiotherapy. One of them is undergoing regular check-ups with complete remission of their tumour 2 years after diagnosis, and the other patient died from a metachronous lung carcinoma and subsequent development of brain metastases.</p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Case 1</span><p id="par0050" class="elsevierStylePara elsevierViewall">A 63-year-old, alcoholic cirrhosis liver transplant candidate with development of hepatocellular carcinoma. The ENT examination revealed a tumour in the left hemitongue about 3 cm of longest diameter. The tumour was staged as cT2N2M0 and underwent concomitant radiotherapy treatment with chemotherapy.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Case 2</span><p id="par0055" class="elsevierStylePara elsevierViewall">A 50-year-old patient presented with a left supraglottic laryngeal tumour and an ipsilateral latero-cervical adenopathy. After biopsy, an infiltrating epidermoid carcinoma stage T4N2BM0 was confirmed and treated with chemoradiotherapy.</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discussion</span><p id="par0060" class="elsevierStylePara elsevierViewall">Performing a liver transplant on a patient with an undiagnosed HNC is extremely harmful both to the patient, by putting his or her health at serious risk, and to the health service involved, taking the direct and indirect costs of the liver transplant (time of admission, surgical procedure, associated complications, immunosuppressive treatment) into account.</p><p id="par0065" class="elsevierStylePara elsevierViewall">The results of our study confirm that in those patients with a history of chronic smoking and/or high alcohol intake, ruling out the presence of a malignant tumour of the head and neck is indicated, since these toxic habits are the main risk factors for the development of these cancers. However, in patients with no history of toxic habits, pre-transplant screening does not seem necessary to rule out tumour disease.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Furthermore, different studies recommend the need for close follow-up of patients already transplanted and with risk factors to rule out the onset of malignant head and neck tumours in subsequent years, taking into account that immunosuppression to avoid transplant rejection is an added risk factor per se.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,9</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">From a review of the literature, we found only one previous study that analysed the usefulness of head and neck examination to rule out malignant tumours in patients who are candidates for liver transplantation.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Out of 581 candidates, only one patient was found to have a malignant tumour, concluding that, given the low detection of HNC, there were doubts about the cost-benefit of this indication.<span class="elsevierStyleSup">10</span> However, the authors did not take into account that performing a liver transplant on a patient with an undiagnosed HNC, in addition to being a serious problem from a medical point of view, will probably increase direct and indirect health costs more than systematic ENT examination in outpatient clinics.</p><p id="par0080" class="elsevierStylePara elsevierViewall">The detection of a malignant head and neck tumour is initially an absolute contraindication for liver transplantation. However, if there is complete remission after locoregional treatment with a disease-free period of 2–5 years, depending on the type of malignant tumour, these patients may again be eligible for liver transplantation.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">In our opinion, it is very valuable to assess patients who are to undergo liver transplantation, taking a history of smoking and alcohol, of symptoms of head and neck neoplasia (dysphonia, dysphagia, odynophagia, otalgia, etc.). Patients with a history of toxic habits and/or head and neck symptoms should then be assessed by an ENT specialist.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conclusions</span><p id="par0090" class="elsevierStylePara elsevierViewall">A pre-transplant head and neck examination is indicated for liver transplant candidates with a history of smoking and/or high alcohol intake, including pharyngeal fibroscopy and neck palpation for screening of synchronous tumours.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflict of interests</span><p id="par0095" class="elsevierStylePara elsevierViewall">The authors have no conflict of interests to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1362646" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1252641" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1362645" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1252640" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Material and methods" ] 6 => array:3 [ "identificador" => "sec0015" "titulo" => "Results" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Case 1" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Case 2" ] ] ] 7 => array:2 [ "identificador" => "sec0030" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0035" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflict of interests" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-11-18" "fechaAceptado" => "2020-02-04" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1252641" "palabras" => array:3 [ 0 => "Liver transplant" 1 => "Head and neck cancer" 2 => "Screening" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1252640" "palabras" => array:3 [ 0 => "Trasplante hepático" 1 => "Cáncer de cabeza y cuello" 2 => "Cribado" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Liver transplantation is the only alternative treatment in patients in end-stage liver function. In many cases the need for liver transplantation is a consequence of the toxic effects of alcohol.</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The aim of our study was to determine if patients who are candidates for a liver transplant require a systematic exploration of the head and neck to rule out malignant lesions in this area.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">All the candidates for a liver transplant, between 2011 and 2017, were included in our study. All of them underwent a systematic exploration of the head and neck by an otolaryngologist to rule out malignancy of the head and neck.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A total of 141 patients were included in our study. In two of them (1.3%) a carcinoma of the head and neck was detected (one of the oropharynx and the other of the larynx). Both patients were asymptomatic from an ENT point of view. They were treated with chemoradiotherapy. One of them died during follow-up due to the appearance of a metachronous lung tumour. The other is free of disease 2 years after diagnosis but without having been transplanted. Both patients had a history of smoking and high alcohol intake.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">In patients who are candidates for a liver transplant who have a history of smoking and / or high alcohol intake, a pretransplant head and neck study including pharyngo-laryngeal fibroscopy is indicated.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducción</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">El trasplante hepático constituye la única alternativa de tratamiento en pacientes con hepatopatías crónicas avanzadas. La etiología más frecuente en nuestro medio es la viral y la alcohólica.</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El objetivo de nuestro estudio fue determinar si los pacientes que son candidatos a un trasplante hepático precisan una exploración de cabeza y cuello de forma sistemática para descartar neoplasias de dicha área.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y métodos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Todos los pacientes candidatos a la realización de un trasplante hepático entre los años 2011 y 2017, fueron incluidos en nuestro estudio. A todos ellos se les realizó de forma sistemática una exploración de cabeza y cuello por un otorrinolaringólogo para descartar neoplasias de cabeza y cuello.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Un total de 141 pacientes fueron incluidos en nuestro estudio. En dos de ellos (1,3%) se detectó un carcinoma de cabeza y cuello (uno de orofaringe y otro de laringe), estando ambos pacientes asintomáticos. Fueron tratados con quimiorradioterapia, falleciendo uno de ellos durante el seguimiento por la aparición de un tumor metacrónico pulmonar. El otro paciente está libre de enfermedad 2 años después del diagnóstico, pero no ha recibido trasplante hepático hasta la fecha. Ambos pacientes tenían antecedentes de tabaquismo y alta ingesta de alcohol.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">En pacientes que son candidatos a un trasplante hepático, y que presentan antecedentes de tabaquismo y/o alta ingesta alcohólica recomendamos la realización de un estudio de cabeza y cuello pretrasplante que incluya exploración nasofibroscópica de las regiones faringo-laríngeas para despistaje de tumores sincrónicos.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Castillo-Ledesma N, Corriols-Noval P, López-Simón E, Viana-Cora A, Casafont-Morencos F, Ezcurra-Acedo I, et al. Cribado de cáncer de cabeza y cuello en pacientes candidatos a trasplante hepático. Acta Otorrinolaringol Esp. 2020;71:249–252.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Bermuda Triangle for the liver: alcohol, obesity, and viral hepatitis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "S. 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