18F-FDG PET/CT in the evaluation of patients suspected of paraneoplastic neurological syndrome | Revista Española de Medicina Nuclear e Imagen Molecular (English Edition)

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La PET/TC muestra nódulos hipermetabólicos a nivel del mesenterio y una dudosa lesión en la ampolla rectal, ya que no se descartaba su relación con eliminación fisiológica, dada la presencia de heces. El diagnóstico final fue un cáncer de recto pT1N0. Los hallazgos en el mesenterio se catalogaron como linfadenitis mesentérica." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A.M. García Vicente, C.H. Vega Caicedo, R. Mondéjar Solís, J.Á. de Ayala Fernández, J.A. Garrido Robles, F.J. Pena Pardo, M. Muñoz Pasadas, P. del Saz Saucedo, G.A. Jiménez Londoño, A. León Martín, Á. Soriano Castrejón" "autores" => array:11 [ 0 => array:2 [ "nombre" => "A.M." "apellidos" => "García Vicente" ] 1 => array:2 [ "nombre" => "C.H." "apellidos" => "Vega Caicedo" ] 2 => array:2 [ "nombre" => "R." "apellidos" => "Mondéjar Solís" ] 3 => array:2 [ "nombre" => "J.Á." "apellidos" => "de Ayala Fernández" ] 4 => array:2 [ "nombre" => "J.A." 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García Vicente, C.H. Vega Caicedo, R. Mondéjar Solís, J.Á. de Ayala Fernández, J.A. Garrido Robles, F.J. Pena Pardo, M. Muñoz Pasadas, P. del Saz Saucedo, G.A. Jiménez Londoño, A. León Martín, Á. Soriano Castrejón" "autores" => array:11 [ 0 => array:4 [ "nombre" => "A.M." "apellidos" => "García Vicente" "email" => array:1 [ 0 => "angarvice@yahoo.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "C.H." "apellidos" => "Vega Caicedo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "R." "apellidos" => "Mondéjar Solís" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "J.Á." 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"apellidos" => "León Martín" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "g" "identificador" => "aff0035" ] ] ] 10 => array:3 [ "nombre" => "Á." "apellidos" => "Soriano Castrejón" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:7 [ 0 => array:3 [ "entidad" => "Servicio de Medicina Nuclear, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Oncología Médica, Hospital Virgen de la Luz, Cuenca, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Medicina Interna, Complejo Hospitalario de Albacete, Albacete, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Neurología, Complejo Hospitalario de Toledo, Toledo, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Servicio de Neurología, Hospital de Puertollano, Ciudad Real, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Servicio de Neurología, Hospital la Mancha Centro, Alcázar de San Juan, Ciudad Real, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Unidad de Investigación, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "PET/TC con 18F-FDG en la valoración de pacientes con sospecha de síndrome paraneoplásico neurológico" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2788 "Ancho" => 3250 "Tamanyo" => 356403 ] ] "descripcion" => array:1 [ "en" => "Patient with a history of Hodgkin's lymphoma, in complete remission presenting cerebellar syndrome and therefore suspected NPS. Previous MRI showed unspecific signs in L2. The PET-CT showed bilateral hypermetabolic laterocervical adenopathy and a hypermetabolic lesion in L2 which did not show on previous PET-CT scans, suggesting infiltration. Diagnosis of recurrent tumour was confirmed." ] ] ] "textoCompleto" => "IntroductionA paraneoplastic syndrome is a set of signs and symptoms, not due to the local presence of primary tumour or metastases but related to the release of factors excreted by tumour cells.The symptoms of paraneoplastic syndromes have been reported in relation with small-cell lung cancer (SCLC), breast cancer and lymphomas, and also ovarian, gastrointestinal and kidney cancers. They often appear before the diagnosis of a malignancy, constituting a first sign of disease; therefore accurate detection is advantageous for early diagnosis of certain neoplasias.<a class="elsevierStyleCrossRef" href="#bib0130">1</a>There are several classifications of paraneoplastic syndromes. They can be endocrine–metabolic, among which the most common are hypercalcaemia – the inappropriate secretion of antidiuretic hormone and Cushing's syndrome. Haematologic paraneoplastic syndromes include polycythaemia which is a syndrome related to hypernephroma, and disseminated intravascular coagulation, with which the most common cancers associated are the mucin-producing adenocarcinomas. There are also neurological paraneoplastic syndromes, in whose pathogenesis immunological factors play an important role.<a class="elsevierStyleCrossRef" href="#bib0135">2</a>Only small number, less than 1%, of cancer sufferers experience neurological paraneoplastic syndrome (NPS). Antigens identical to those expressed by neural tissues are expressed by the tumour and are called onconeural antigens.<a class="elsevierStyleCrossRef" href="#bib0140">3</a> These are recognised by the immune system triggering an anti-tumour immune response – the production of onconeural antibodies – which may be partially, or rarely, completely effective; on other occasions the response leads to NPS.18F-FDG PET-CT has been described as being advantageous over conventional imaging techniques in diagnosing NPS. However, most of these studies were retrospective, some with limited sample of patients.<a class="elsevierStyleCrossRefs" href="#bib0145">4–6</a> Some authors describe PET as an overvalued technique in the detection of occult neoplasms in patients with NPS<a class="elsevierStyleCrossRef" href="#bib0160">7</a>; however other studies report high sensitivity and specificity in the evaluation of NPS and suggest PET as a valuable tool in clinically suspected NPS.<a class="elsevierStyleCrossRefs" href="#bib0165">8,9</a>The study aimed to determine the diagnostic value of 18F-FDG PET-CT in establishing the origin of occult malignancy based on the clinical features of NPS.Material and methodsA longitudinal multicenter retrospective study of 18F-FDG PET-CT scans performed in patients suspected of NPS who had been referred to us from various hospitals between November 2006 and December 2013.PatientsInclusion criteria were clinically suspected NPS and confirmed diagnosis by biopsy or 12-month minimum clinical/radiological follow-up after PET-CT.Exclusion criteria were diagnosis of neoplasia, be it active, initial or a recurrence of an old known neoplastic process, in the 6 months prior to PET-CT, or absence of final NPS diagnostic confirmation. Therefore, in the case of patients with previous oncological history, only patients in complete remission confirmed by clinical/radiological follow-up for at least the previous 6 months were included.Data were collected and recorded as to the age, sex and previous oncological history of patients, specifying the origin of the primary tumour.All patients had had at least one negative or inconclusive CT and/or MRI within the three months prior to the PET-CT.The syndromes presented by the patients suspected of being paraneoplastic in nature were categorised according to Graus classification<a class="elsevierStyleCrossRef" href="#bib0175">10</a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). They were recorded as either classical paraneoplastic syndrome (CS) or non-classical (NCS). Symptoms/signs that did not fit any of these categories were grouped as unclassifiable.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Tests for onconeural antibodies were performed, to determine them on a molecular level as having either characteristic association with cancer or as other antibodies with abilities to associate with neoplasias.<a class="elsevierStyleCrossRef" href="#bib0180">11</a>After confirmation of the diagnosis, the NPS was classified as either definite or possible according Graus<a class="elsevierStyleCrossRef" href="#bib0175">10</a> criteria (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). Symptoms/signs that did not fit as either definite or possible were categorised as unclassifiable.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Methodology of PET-CT with 18F-FDG imaging and interpretationA hybrid PET-CT scanner was used to obtain images 60min after administration of 370MBq of 18F-FDG. Images were obtained from the orbital–meatal line to the proximal third of the lower limbs. First, low-dose CT images were acquired (120kV, 80mAs), followed by PET in three-dimensional (3D) mode with an acquisition time of 3min per bed.PET images were reconstructed using CT images for attenuation correction and having applied the iterative reconstruction algorithm.Images were blindly assessed by two nuclear medicine physicians, and in the case of non-concordance, a third specialist was consulted.18F-FDG PET-CT studies were classified as:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">-Normal. No focal uptake outside expected physiological locations.</li><li class="elsevierStyleListItem" id="lsti0010">-Probably malignant. Evidence of focal hotspot, regardless of degree of uptake, located in organs or structures that could house a primary tumour and not related to physiological processes.</li><li class="elsevierStyleListItem" id="lsti0015">-Doubtful. FDG focal uptake, difficult to differentiate malignancy from inflammation, for example, isolated or multiple lymphadenopathy, thyroid nodules, etc.</li></ul>For the purposes of binary analysis, ‘probably malignant’ and ‘doubtful’ were considered positive, and ‘normal’ studies were classified as negative.The definitive diagnosis, being of either neoplastic process or not, was established based on histopathological reports, from a biopsy or taken in surgery. Negative diagnosis was confirmed after clinical/radiological follow-up over 12 months from the date of 18F-FDG PET-CT.Statistical analysisThe results of 18F-FDG PET-CT studies and those of the other variables (clinical signs and symptoms, final NPS and onconeuronal antibody classification) were compared. Differences were analysed using Pearson's Chi-squared test (χ2), likelihood ratio, and Cochran–Mantel–Haenszel (CMH) test. The correlations between the results of 18F-FDG PET-CT with the final diagnosis and its relationship with the type of NPS were also analysed. In all cases p<0.05 was considered significant.ResultsSixty-four patients (42 men and 22 women) were included, with an average age of 62±14 years. The average follow-up time was 25±19 months.Six patients had prior oncological history (and were in complete clinical remission) at the time of the PET-CT request. These included cases of Hodgkin's lymphoma (HL), breast cancer, uterine cancer, rectal cancer and two cases of prostate cancer.In ten patients the final diagnosis of neoplasia was confirmed, constituting the final NPS group. Seven corresponded to invasive neoplasia and the remaining three were confirmed as a high-grade dysplasia of the cervix, an in situ cervical carcinoma and a mature ovarian teratoma. In <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> patient characteristics are listed. Excluding the three non-invasive cancer cases, PET-CT was helpful in locating malignancy in 5 of 7 patients, representing a sensitivity of 71%.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>After the removal of the primary tumour, symptoms persisted in 3 cases: sensory polyneuropathy of the lower limbs in the patient with in situ cervical cancer, cerebellar syndrome in the patient with relapsed HL (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) and limbic encephalitis in a patient with SCLC (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Three patients died (recurrence of breast cancer and prostate cancer and one patient with SCLC). In the remaining cases neurological symptoms disappeared after removal of the primary tumour.<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia>Eight patients had positive results for onconeural antibodies. Four of these belonged to the group of patients finally diagnosed with neoplastic syndrome, detailed in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>. The other four cases, all with negative PET-CT, corresponded to:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020">-Patient with a history of prostate cancer undergoing androgen deprivation therapy in remission (undetectable PSA) with CS and positive for Ma2/Ta. This patient has had 2 negative PET-CT results, and is being treated with immunotherapy responding partially. The origin of the neoplasia is undiagnosed.</li><li class="elsevierStyleListItem" id="lsti0025">-NCS patient, positive for amphiphysin antibodies, unidentified origin of the neoplastic process and partial response to treatment with immunotherapy.</li><li class="elsevierStyleListItem" id="lsti0030">-Two patients with NCS positive for anti-HU. Both catalogued with polyneuropathy of unknown origin, and neoplastic process was not determined during follow-up.</li></ul>In 35 patients antibody determination was not performed and in 21 patients results were negative.The syndromes of patients analysed were classified as CS in nineteen cases (30%) and NCS in twenty-seven (42%) cases. Eighteen cases (28%) did not fit either NCS or CS definitions, so were labelled unclassifiable.Ten (16%) cases were confirmed as definite NPS, thirteen (20%) cases classified as possible NPS, and the remaining cases were considered unclassifiable.PET-CT was classified as positive in seven of ten (70%) patients with definite NPS. PET-CT was positive in only two patients (15%) with possible NPS and normal in eleven (85%) patients with possible NPS. <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> details the results.<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>Statistical analysis of the results found a significant relationship (p=0.001) between the clinical classification of NPS (SC vs. SNC) and the final diagnosis (definite NPS vs possible). SC patients were more likely to be associated with final NPS than those with NCS (38% vs 16%).We also found that most of the cases classified as NCS (18; 72%) and all the clinically unclassifiable cases (16; 100%) did not fit either of the final diagnostic categories (definite NPS vs possible). That is to say, cases with very low clinical suspicion of NPS were associated with other final diagnoses unrelated to this entity.76.2% of patients with negative PET-CT had negative results for onconeuronal antibodies (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).There was no statistical significance between the final diagnosis of the syndrome (definite NPS vs possible) after follow-up and the results of the PET-CT (p=0.08), although we noted that there were a higher proportion of positive studies PET-CT in patients with definite NPS and more negative studies in the NPS possible cases.Two positive PET-CTs with findings corresponding to suspect malignancy, were due to mesenteric nodules and were finally classified as lymphadenitis. They corresponded to a patient with rectal cancer, with no locally affected lymph nodes, and a suspected lesion in the rectal ampulla as shown on the PET-CT (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>) and another patient without proven malignancy who was eventually diagnosed with Parkinson-plus syndrome.<elsevierMultimedia ident="fig0015"></elsevierMultimedia>The remaining sixteen of the cases with doubtful PET findings were:<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0035">-Pseudonodular breast lesion with moderate metabolism associated in the patient with in situ cervical carcinoma. The mammography was normal.</li><li class="elsevierStyleListItem" id="lsti0040">-Three cases of thyroid nodules with detected metabolism. No biopsy was performed in two of the cases, and the third died.</li><li class="elsevierStyleListItem" id="lsti0045">-Nonspecific mediastinal adenopathy with/without associated lung lesions in eight cases. The lung lesions consisted of infiltrates or pseudonodules in three cases. Complementary imaging tests did not suggest the need for biopsies.</li><li class="elsevierStyleListItem" id="lsti0050">-Other adenopathies included: two laterocervical, one supradiaphragmatic and one infradiaphragmatic with low metabolism. Findings were not suspected of malignancy and therefore not recommended for biopsy.</li><li class="elsevierStyleListItem" id="lsti0055">-Nodular/pseudonodular lung lesions with detectable metabolism. They corresponded to a patient with a previous pneumonia months before the PET-CT and therefore were suggestive of residual inflammatory processes. The patient died in the following months without a definitive diagnosis being established.</li></ul>DiscussionSigns and symptoms resulting from damage to any part of the nervous system through immunological means, and neoplastic aetiology are what are called NPS. The symptoms usually present at a distance from the primary tumour or metastasis and often precede, by years, the clinical underlying manifestations of the neoplastic process.<a class="elsevierStyleCrossRef" href="#bib0175">10</a>The response to the onconeural antigens is the production of anti-neuronal antibodies which can cross the blood brain barrier and attack the central or peripheral nervous system. These antibodies can be detected in blood plasma or cerebrospinal fluid. However, only a minority of the patients with these antibodies present neurological symptoms.<a class="elsevierStyleCrossRef" href="#bib0185">12</a>In approximately 60% of patients with NPS, highly specific onconeural antibodies are found.<a class="elsevierStyleCrossRef" href="#bib0190">13</a> However, although some of these antibodies are present more frequently in certain tumours, their detection is neither sensitive nor specific enough for diagnosis. This means that not all NPS will imply positivity for onconeural antibodies, and not all patients with positive antibodies will have NPS. In fact, not all the patients who present onconeural antibodies are diagnosed with malignant disease or have tumours detected in autopsy.<a class="elsevierStyleCrossRefs" href="#bib0155">6,14,15</a>The diagnostic sensibility of PET in NPS is between 75% and 100%. In <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a> an overview of the main studies is shown.<elsevierMultimedia ident="tbl0025"></elsevierMultimedia>The percentage of positivity for anti-neuronal antibodies in studies which have used metabolic imaging looking for malignancy is variable, between 10% and 53%.<a class="elsevierStyleCrossRefs" href="#bib0160">7,9</a> In this study eight of the twenty-nine patients for whom onconeural antibody tests were requested were positive; the true utility of this parameter in our population is unknown.Previous studies have shown a relationship between the presence of onconeural antibodies and a positive PET result.<a class="elsevierStyleCrossRefs" href="#bib0155">6,16,17</a> For this reason, given the possible influence of the positivity of the onconeural antibodies in the PET results, some authors have recommended the use of FGD-PET-CT in cases of high clinical suspicion, and well characterised antibodies. Mckeon et al.<a class="elsevierStyleCrossRef" href="#bib0150">5</a> found a statistically significant association between the presence of antibodies and successful localisation of neoplasia with PET: 70% of patients with cancer came up positive for antibodies, and only 14% of patients without cancer. Rees el al.<a class="elsevierStyleCrossRef" href="#bib0145">4</a> found positivity for antibodies in 43% of positive PET cases, compared with 16% of negative PET cases, although the differences were not statistically significant. In our study, 76% of patients negative for onconeural antibodies had a negative FDG-PET-CT (p=0.36) although the reduced number of cases limits the reliability of drawn conclusions.On one hand, the dilemma remains regarding the treatment of patients positive for onconeural antibodies yet no neoplasia was detected in PET. Patel et al.<a class="elsevierStyleCrossRef" href="#bib0155">6</a> found that in 63 of 73 patients positive for antibodies and negative PET, there was no neoplasia found after extensive study and follow-up, leading to the hypothesis that the very same antibodies had actually led to the destruction of the tumour, either that or the tumour was so small it was undetectable.<a class="elsevierStyleCrossRef" href="#bib0175">10</a> In 2006 the Paraneoplastic Neurological Syndrome Euronetwork recommended a five-year follow-up period before declaring absence of occult malignancy in a patient.<a class="elsevierStyleCrossRef" href="#bib0215">18</a> Regarding period of control in cases positive for antibodies where no neoplasia was detected, the European Federation of Neurological Societies recommends repeating screening tests every six months for four years, except in cases of Lambert–Eaton myasthenic syndrome (LEMS) in which two years would be sufficient.<a class="elsevierStyleCrossRef" href="#bib0220">19</a>Some authors define PET as the best technique available, although the guides do not mention PET during follow-up.<a class="elsevierStyleCrossRef" href="#bib0205">16</a>On the other hand, patients may well have NPS without onconeural antibodies.<a class="elsevierStyleCrossRef" href="#bib0175">10</a> Hadjivassiliou et al.<a class="elsevierStyleCrossRef" href="#bib0165">8</a> mention in their study that only 50% of patients with malignant disease, as proven by biopsy, were positive for onconeural antibodies. In these cases, metabolic imaging has resulted superior to conventional images.<a class="elsevierStyleCrossRefs" href="#bib0145">4,6,16,17,20</a> That is why the European Federation of Neurological Societies recommends PET when morphological imaging tests come up negative.<a class="elsevierStyleCrossRef" href="#bib0220">19</a> However, it seems that this diagnostic sequence, given the hybrid character of PET-CT is not strictly necessary. Schramm et al.<a class="elsevierStyleCrossRef" href="#bib0230">21</a> in a cohort study of patients with NPS found that PET-CT with intravenous contrast showed higher sensitivity and specificity than the CT with contrast alone (100% and 90% vs 78% and 88%). In our sample of patients finally diagnosed with a tumour, two were negative for antibodies, and in four cases they did not undergo the antibody test (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).So, although the presence of onconeural antibodies should not be a requisite for the realisation of PET in NPS, the serological evidence of these antibodies may be of use in improving the diagnostic performance of PET.<a class="elsevierStyleCrossRef" href="#bib0165">8</a>SCLS constitutes one of the principal causes of NPS. In cases of positivity for the anti-Hu antibody associated with the paraneoplastic syndrome, the metastases of SCLC are often limited to the mediastinum.<a class="elsevierStyleCrossRef" href="#bib0230">21</a> In a study including patients positive for onconeuronal antibodies, 80% of the patients with SCLC were found to have central mediastinal tumours. In these cases, PET was positive in 100% of the cases, while sensitivity of CT was 50%.<a class="elsevierStyleCrossRef" href="#bib0235">22</a> In our sample PET-CT detected mediastinal adenopathy with pathological metabolism in the two cases of SCLC.Regarding the clinical characteristics of NPS, very few published works have analysed the character of the neurological symptomology in order to categorise the syndrome as either CS or NCS. The percentage of patients with NPS categorised as CS is variable, and ranges between 37% and 62% in studies which have used metabolic images.<a class="elsevierStyleCrossRefs" href="#bib0160">7,9</a> Previous studies have documented a different diagnostic performance of PET when considering the presence of CS or not, finding higher rates of abnormal PET in patients with CS (41%) than patients with NCS (21%); concluding that PET performs better in classical paraneoplastic syndromes.<a class="elsevierStyleCrossRef" href="#bib0165">8</a> In our study, classifying the patients as definite or possible NPS, we found that 60% of the definite NPSs had a positive PET-CT and 85% of the possible NPSs had a negative PET-CT (p=0.08).Regarding false positives (FP) in PET, the prevalence seems high.<a class="elsevierStyleCrossRef" href="#bib0155">6</a> The fact that in many cases the tumours associated with NPS are small – often with only lymph node metastases – means that the study must be more exhaustive, unfortunately increasing the FP rate. Given the poor specificity of PET, the correct classification of some lesions with positive metabolism is difficult. In our sample eighteen studies had doubtful results, in the end classified as FP, with adenopathy being the most prevalent type. In three cases, patients presented thyroid nodules with increased metabolism. Similar findings have also been reported previously.<a class="elsevierStyleCrossRef" href="#bib0150">5</a>As regards false negative results, Patel et al.<a class="elsevierStyleCrossRef" href="#bib0155">6</a> found that PET was unable to detect malignancy in two cases of neoplasia of gynaecological origin. In our study, we also had limited ability to detect the three cases of gynaecological disease. The fact that two of these cases corresponded to non-invasive tumours and the third was a non-malignant mature teratoma, we think explains the lack of metabolic detectability; however, we decided to include them as false negative PET-CT. In the case of the teratoma, the patient had onconeural antibodies against the N-methyl-d-aspartate receptor. The symptoms of encephalitis disappeared after the removal of the tumour and the patient remained asymptomatic during the follow-up period. Although not part of the objectives of this study, it was interesting to see that encephalitis caused by anti-N-methyl-d-aspartate receptor onconeuronal antibodies can be associated with cerebral hypo-metabolism.<a class="elsevierStyleCrossRef" href="#bib0240">23</a>Concerning limitations, the low prevalence of malignancy in our sample of patients led to a more effective analysis of the diagnostic performance of PET-CT. This issue has meant that authors have referred to the PET-CT as over-valued regarding to its role in the detection of occult neoplasia in patients with NPS. <a class="elsevierStyleCrossRef" href="#bib0160">7</a>These authors suggest that PET-CT be reserved only for patients with high index of clinical suspicion of NPS and after negative conventional imaging studies. However these authors studied a limited sample of patients, with low prevalence of malignancy. Our detectability rate coincided with those of previous authors, if we take into account the sample of patients finally diagnosed with invasive cancers. In sight of these results, we think that a more careful selection of patients would lead to a higher detectability of malignancy rate, a reduction in false positives, and therefore the optimisation of PET-CT use.Furthermore, the limited knowledge of the state of onconeural antibodies, and the low prevalence of positivity probably limited the ability to find associations with PET-CT results.The reduced follow-up period could have led to false diagnosis if the patient was still developing a potentially detectable malignancy, a process which can last up to five years after the appearance of neurological symptoms. However, in spite of its relevance, we do not think this fact conditioned the final diagnostic result of our patient sample significantly, given the lack of positive onconeural antibody results in some cases and that many of these syndromes did not correspond to CS, which reduces the probability that they originated from a neoplastic process. Equally the fact that patients with previously known neoplasia were included in the study, even in clinical remission, could have conditioned some of the results, especially because the set remission period (6 months) may not have been enough.Considering the strong points, this study analysed a considerable sample of patients with clinical suspicion of NPS. They were categorised as either CS or NCS, and studied with the onconeural antibody results in order to try to define the implications of these variables in the results of PET-CT, and in the establishment of the neoplastic origin of the syndrome. We consider these circumstances, seen in very few studies so far as fundamental for the correct determination of diagnostic performance in PET-CT.Moreover, the results of our study, in spite of the low prevalence, of invasive type malignance (11%), reflect the potential of 18FDG-PET-CT in the evaluation of patients with suspected NPS at a sensitivity of 71%.ConclusionIn spite of low prevalence of malignancy in our series, PET-CT detected malignancy in a significant proportion of patients with invasive cancer.The presence of anti-onconeural antibodies and the clinical characteristics of NPS seem to be relevant conditions for the diagnostic indication of PET-CT with 18F-FDG.Conflict of interestThe authors declare no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres526485" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec546672" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres526484" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec546671" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Methodology of PET-CT with F-FDG imaging and interpretation" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0030" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0035" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Conclusion" ] 9 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflict of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-12-11" "fechaAceptado" => "2015-02-27" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec546672" "palabras" => array:4 [ 0 => "Paraneoplastic neurological syndrome" 1 => "Clinical classification" 2 => "PET/CT" 3 => "18F-FDG" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec546671" "palabras" => array:4 [ 0 => "Síndrome paraneoplásico neurológico" 1 => "Clasificación clínica" 2 => "PET/TC" 3 => "18F-FDG" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveThis study aimed to determine the diagnostic impact of 18F-FDG PET/CT based on the clinical features of paraneoplastic neurological syndrome (PNS). Material and methodsMulticenter retrospective and longitudinal study of patients with suspicion of PNS.The clinical picture was classified into classic (CS) and non-classic syndrome (NCS). After the follow-up, the definitive or possible diagnosis of PNS was established. The pictures that did not match any of the previous criteria were categorised as non-classifiable. The state of the onconeural antibodies was studied.The PET/CT was classified as positive or negative for the detection of malignancy. The relationship between PET/CT findings and the final diagnosis was determined. The differences between variables (Pearson test X2) and the relationship between the results of the PET/CT and the final diagnosis was analysed. ResultsA total of 64 patients were analysed, classifying 30% as CS and 42% as NCS. After the follow-up, 20% and 16% of subjects were diagnosed as possible and definitive PNS, respectively. Positive onconeural antibodies were found in 13% of the patients.A definitive diagnosis of PNS was associated with a positive PET/CT (p=.08). A significant relation between antibodies expression and final diagnosis of neoplasia (p=.04) was demonstrated.The PET/CT correctly localised malignancy in 5/7 cases of invasive cancer. ConclusionsThe PET/CT showed a higher percentage of positive results in patients with definitive diagnosis of PNS. Despite the low prevalence of malignancy in our series, the PET/CT detected malignancy in a significant proportion of patients with invasive cancer." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivoDefinir el impacto diagnóstico de la PET/TC con 18F-FDG en función de las características clínicas del síndrome paraneoplásico neurológico (SPN). Material y métodosEstudio retrospectivo multicéntrico y longitudinal de pacientes con sospecha de SPN.El cuadro clínico se clasificó en síndrome clásico (SC) o no clásico (SNC). Tras el seguimiento se estableció el diagnóstico de SPN definitivo o posible. Los cuadros que no encajaron en ninguna de las categorías previas se catalogaron como no clasificables. Se analizó el estado de los anticuerpos onconeuronales.La PET/TC se clasificó en positiva o negativa para la detección de malignidad. Se determinó la relación entre los hallazgos PET/TC y el diagnóstico final. Se analizaron las diferencias entre variables (Chi cuadrado de Pearson) y la relación entre el resultado de la PET/TC y el diagnóstico definitivo. ResultadosSe analizaron 64 pacientes. El 30% de los cuadros clínicos se catalogaron como SC y el 42% como SNC. Tras el seguimiento el 20% se clasificó en SPN posible y el 16% en definitivo. El 13% de los pacientes tenía anticuerpos onconeuronales positivos.El hecho de poseer un SPN definitivo se relacionó con un resultado positivo de la PET/TC (p=0,08). Se demostró relación significativa entre la positividad de los anticuerpos y el diagnóstico final de proceso neoplásico (p=0,04).La PET/TC fue eficaz en la correcta localización tumoral en 5/7 casos con cáncer invasivo. ConclusionesLa PET-TC mostró un mayor porcentaje de resultados positivos en pacientes con diagnóstico de SPN definitivo. A pesar de la baja prevalencia de malignidad en nuestra serie, la PET/TC detectó malignidad en una significativa proporción de pacientes con cáncer invasivo." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: García Vicente AM, Vega Caicedo CH, Mondéjar Solís R, de Ayala Fernández JA, Garrido Robles JA, Pena Pardo FJ, et al. PET/TC con 18F-FDG en la valoración de pacientes con sospecha de síndrome paraneoplásico neurológico. Rev Esp Med Nucl Imagen Mol. 2015;34:236–243." ] ] "multimedia" => array:8 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2788 "Ancho" => 3250 "Tamanyo" => 356403 ] ] "descripcion" => array:1 [ "en" => "Patient with a history of Hodgkin's lymphoma, in complete remission presenting cerebellar syndrome and therefore suspected NPS. Previous MRI showed unspecific signs in L2. The PET-CT showed bilateral hypermetabolic laterocervical adenopathy and a hypermetabolic lesion in L2 which did not show on previous PET-CT scans, suggesting infiltration. Diagnosis of recurrent tumour was confirmed." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 915 "Ancho" => 3252 "Tamanyo" => 167767 ] ] "descripcion" => array:1 [ "en" => "Patient with limbic encephalitis, positive for onconeural antibodies (amphiphysin). Previous CT study produced inconclusive findings. In the PET-CT hypermetabolic adenopathy in the aortopulmonary window and ipsilateral hilum was observed. Pathology report confirmed SCLC." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2563 "Ancho" => 3250 "Tamanyo" => 474385 ] ] "descripcion" => array:1 [ "en" => "Patient with CS and positive for neuron-specific enolase. PET-CT shows hypermetabolic mesenteric nodules and a doubtful lesion in the rectal ampulla (perhaps due to physiological elimination, presence of faeces). The final diagnosis was pT1N0 rectal cancer. The findings in the mesentery were catalogued as mesenteric lymphadenitis." ] ] 3 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Source: Graus et al.<a class="elsevierStyleCrossRef" href="#bib0175">10</a>" "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Syndromes of the central nervous system</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">ClassicalEncephalomyelitisLimbic encephalitisSub-acute cerebellar degenerationOpsoclonus myoclonus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Non-classicalBrainstem encephalitisStiff person syndromeOptic neuritisCancer associated retinopathyNecrotising myelopathy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Syndromes of the peripheral nervous system</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">ClassicalSub-acute sensory neuronopathyChronic gastrointestinal pseudo-obstruction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Non-classicalGuillain-Barré syndromeBrachial neuritisAcute pandysautonomiaNeuropathy with vasculitisNeuropathy and paraproteinaemia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Syndromes of the neuromuscular junction and muscle</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">ClassicalLambert-Eaton myasthenic syndromeDermatomyositis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Non-classicalMyasthenia gravisAcquired neuromyotoniaAcute necrotising myopathy \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab848262.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Classical and non-classical paraneoplastic neurological syndromes according to Graus et al." ] ] 4 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Source: Graus et al.<a class="elsevierStyleCrossRef" href="#bib0175">10</a>" "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Definite NPS \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">A classical syndrome and cancer, with or without onconeural antibodies, that develops within five years of the diagnosis of the neurological disorder \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">A non-classical syndrome that resolves or significantly improves after cancer treatment without concomitant immunotherapy, provided that the syndrome is not susceptible to spontaneous remission. \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">A non-classical syndrome with onconeural antibodies (well characterised or not) and cancer that develops within five years of the diagnosis of the neurological disorder. \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">A neurological syndrome (classical or not) with well characterised onconeural antibodies (anti-Hu (ANNA-1), Yo (CA-1), CV2 (CMPR5), Ri (ANNA-2), Ma2, or amphiphysin), and no cancer. \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"> \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">Possible NPS \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">A classical syndrome, no onconeural antibodies, no cancer but at high risk to have an underlying tumour (for example heavy smoker or over 50 years of age) \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">A neurological syndrome (classical or not) with partially characterised onconeural antibodies and no cancer.A non-classical syndrome, no onconeural antibodies, and cancer present within two years of diagnosis. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab848261.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Diagnostic criteria for paraneoplastic neurological syndromes according to Graus et al." ] ] 5 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "A: age; Ab: antibodies; CS: classical syndrome; F: female; FDG: fluorodeoxyglucose; M: male; NCS: non-classical syndrome; NR: not requested; NPS: neurological paraneoplastic syndrome; PET-CT: positron emission tomography-computed tomography; SCLC: small cell lung cancer." "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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">G/A (yrs) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">NPS \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Previous neoplasm \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Onconeural Ab. \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">FDG PET-CT findings \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Final diagnosis \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">M/64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hodgkin's lymphoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hypermetabolic supradiaphragmatic adenopathy and bone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Recurrent lymphoma \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">M/70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NCS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prostate cancer \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hypermetabolic inguinal adenopathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Recurrent prostate cancer \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">F/61 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Breast cancer \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Anti-Yo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hypermetabolic inguinal adenopathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Recurrent breast cancer \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">F/51 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NCS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Pseudonodular breast lesion with moderate metabolism \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">in situ cervical carcinoma \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">M/54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hypermetabolic mesenteric nodules \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rectal cancer \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">F/28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Anti-NMDA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Negative (ametabolic cyst) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mature ovarian teratoma \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">M/81 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amphiphysin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hypermetabolic mediastinal adenopathy and in pulmonary hilum. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SCLC \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">M/65 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NCS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prostate cancer \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">F/70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NCS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">High grade cervical dysplasia \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">M/56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NCS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ANNA1-MAG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hypermetabolic mediastinal adenopathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SCLC \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab848258.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Results obtained in the 10 patients diagnosed with malignancy." ] ] 6 => array:7 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "Ab: antibodies; NPS: neurological paraneoplastic syndrome; PET-CT: positron emission tomography-computed tomography." "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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variables \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Positive PET-CT \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Negative PET-CT \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top">Onconeural Ab</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Positive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (50%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (50%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.36 \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">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (24%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16 (76%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top">NPS<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Definite \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (60%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (40%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.08 \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">Possible \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (15%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 (85%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab848259.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Unreported cases correspond to unclassifiable syndromes." ] ] ] "descripcion" => array:1 [ "en" => "Relationship between the clinical variables and the PET-CT results." ] ] 7 => array:7 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "mod GC: modified gamma camera; N: number of patients; NPS: neurological paraneoplastic syndrome; P: prospective study; PET-CT: positron emission tomography-computed tomography; R: retrospective study; Se: sensitivity; CTivc: computed tomography with intravenous contrast." "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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Author, year, study \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">N \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Methodology \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PET positive; Se \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Malignancy<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Antoine, 2000, R<a class="elsevierStyleCrossRef" href="#bib0210">17</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PET \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3; 100% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \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">Rees, 2001, R<a class="elsevierStyleCrossRef" href="#bib0145">4</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">43 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PET \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16; 88% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \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">Berner, 2003, R<a class="elsevierStyleCrossRef" href="#bib0245">24</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PET \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7; 86% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \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">Younes-Mhenni, 2004, P<a class="elsevierStyleCrossRef" href="#bib0205">16</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PET \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18; 83% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14 \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">Linke, 2004, R<a class="elsevierStyleCrossRef" href="#bib0225">20</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PET \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9, 90% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \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">Patel, 2008, R<a class="elsevierStyleCrossRef" href="#bib0155">6</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">107 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PET \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24; 80% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \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">Hadjivassiliou, 2009, P<a class="elsevierStyleCrossRef" href="#bib0165">8</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">mod GC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18; 75% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \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">Bannas, 2010, R<a class="elsevierStyleCrossRef" href="#bib0160">7</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PET-CT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10; 100% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 \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">Mc Keon, 2010, R<a class="elsevierStyleCrossRef" href="#bib0150">5</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PET-CT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">22, 100% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \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">Matsuhisa, 2012, R<a class="elsevierStyleCrossRef" href="#bib0250">25</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PET-CT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6; 100% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \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">Vaidyanathan, 2012, R<a class="elsevierStyleCrossRef" href="#bib0170">9</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">68 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PET-CT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26; 100% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \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">Schramm, 2013, R<a class="elsevierStyleCrossRef" href="#bib0230">21</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PET-CTivc \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10; 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18F-FDG PET/CT in the evaluation of patients suspected of paraneoplastic neurological syndrome

PET/TC con 18F-FDG en la valoración de pacientes con sospecha de síndrome paraneoplásico neurológico

A.M. García Vicentea,

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angarvice@yahoo.es

Corresponding author.

, C.H. Vega Caicedoa, R. Mondéjar Solísb, J.Á. de Ayala Fernándezc, J.A. Garrido Roblesd, F.J. Pena Pardoa, M. Muñoz Pasadase, P. del Saz Saucedof, G.A. Jiménez Londoñoa, A. León Martíng, Á. Soriano Castrejóna

a Servicio de Medicina Nuclear, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain

b Servicio de Oncología Médica, Hospital Virgen de la Luz, Cuenca, Spain

c Servicio de Medicina Interna, Complejo Hospitalario de Albacete, Albacete, Spain

d Servicio de Neurología, Complejo Hospitalario de Toledo, Toledo, Spain

e Servicio de Neurología, Hospital de Puertollano, Ciudad Real, Spain

f Servicio de Neurología, Hospital la Mancha Centro, Alcázar de San Juan, Ciudad Real, Spain

g Unidad de Investigación, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain

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They can be endocrine&#8211;metabolic&#44; among which the most common are hypercalcaemia &#8211; the inappropriate secretion of antidiuretic hormone and Cushing&#39;s syndrome&#46; Haematologic paraneoplastic syndromes include polycythaemia which is a syndrome related to hypernephroma&#44; and disseminated intravascular coagulation&#44; with which the most common cancers associated are the mucin-producing adenocarcinomas&#46; There are also neurological paraneoplastic syndromes&#44; in whose pathogenesis immunological factors play an important role&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Only small number&#44; less than 1&#37;&#44; of cancer sufferers experience neurological paraneoplastic syndrome &#40;NPS&#41;&#46; Antigens identical to those expressed by neural tissues are expressed by the tumour and are called onconeural antigens&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">3</span></a> These are recognised by the immune system triggering an anti-tumour immune response &#8211; the production of onconeural antibodies &#8211; which may be partially&#44; or rarely&#44; completely effective&#59; on other occasions the response leads to NPS&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleSup">18</span>F-FDG PET-CT has been described as being advantageous over conventional imaging techniques in diagnosing NPS&#46; However&#44; most of these studies were retrospective&#44; some with limited sample of patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">4&#8211;6</span></a> Some authors describe PET as an overvalued technique in the detection of occult neoplasms in patients with NPS<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">7</span></a>&#59; however other studies report high sensitivity and specificity in the evaluation of NPS and suggest PET as a valuable tool in clinically suspected NPS&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">8&#44;9</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The study aimed to determine the diagnostic value of <span class="elsevierStyleSup">18</span>F-FDG PET-CT in establishing the origin of occult malignancy based on the clinical features of NPS&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><p id="par0035" class="elsevierStylePara elsevierViewall">A longitudinal multicenter retrospective study of <span class="elsevierStyleSup">18</span>F-FDG PET-CT scans performed in patients suspected of NPS who had been referred to us from various hospitals between November 2006 and December 2013&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients</span><p id="par0040" class="elsevierStylePara elsevierViewall">Inclusion criteria were clinically suspected NPS and confirmed diagnosis by biopsy or 12-month minimum clinical&#47;radiological follow-up after PET-CT&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Exclusion criteria were diagnosis of neoplasia&#44; 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They were recorded as either classical paraneoplastic syndrome &#40;CS&#41; or non-classical &#40;NCS&#41;&#46; Symptoms&#47;signs that did not fit any of these categories were grouped as unclassifiable&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Tests for onconeural antibodies were performed&#44; to determine them on a molecular level as having either characteristic association with cancer or as other antibodies with abilities to associate with neoplasias&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">11</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">After confirmation of the diagnosis&#44; the NPS was classified as either definite or possible according Graus<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">10</span></a> criteria &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; Symptoms&#47;signs that did not fit as either definite or possible were categorised as unclassifiable&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Methodology of PET-CT with <span class="elsevierStyleSup">18</span>F-FDG imaging and interpretation</span><p id="par0075" class="elsevierStylePara elsevierViewall">A hybrid PET-CT scanner was used to obtain images 60<span class="elsevierStyleHsp" style=""></span>min after administration of 370<span class="elsevierStyleHsp" style=""></span>MBq of <span class="elsevierStyleSup">18</span>F-FDG&#46; 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No focal uptake outside expected physiological locations&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0100" class="elsevierStylePara elsevierViewall">Probably malignant&#46; Evidence of focal hotspot&#44; regardless of degree of uptake&#44; located in organs or structures that could house a primary tumour and not related to physiological processes&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0105" class="elsevierStylePara elsevierViewall">Doubtful&#46; FDG focal uptake&#44; difficult to differentiate malignancy from inflammation&#44; for example&#44; isolated or multiple lymphadenopathy&#44; thyroid nodules&#44; <span class="elsevierStyleItalic">etc&#46;</span></p></li></ul></p><p id="par0110" class="elsevierStylePara elsevierViewall">For the purposes of binary analysis&#44; &#8216;probably malignant&#8217; and &#8216;doubtful&#8217; were considered positive&#44; and &#8216;normal&#8217; studies were classified as negative&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">The definitive diagnosis&#44; being of either neoplastic process or not&#44; was established based on histopathological reports&#44; from a biopsy or taken in surgery&#46; Negative diagnosis was confirmed after clinical&#47;radiological follow-up over 12 months from the date of <span class="elsevierStyleSup">18</span>F-FDG PET-CT&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistical analysis</span><p id="par0120" class="elsevierStylePara elsevierViewall">The results of <span class="elsevierStyleSup">18</span>F-FDG PET-CT studies and those of the other variables &#40;clinical signs and symptoms&#44; final NPS and onconeuronal antibody classification&#41; were compared&#46; Differences were analysed using Pearson&#39;s Chi-squared test &#40;<span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span>&#41;&#44; likelihood ratio&#44; and Cochran&#8211;Mantel&#8211;Haenszel &#40;CMH&#41; test&#46; The correlations between the results of <span class="elsevierStyleSup">18</span>F-FDG PET-CT with the final diagnosis and its relationship with the type of NPS were also analysed&#46; In all cases <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 was considered significant&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><p id="par0125" class="elsevierStylePara elsevierViewall">Sixty-four patients &#40;42 men and 22 women&#41; were included&#44; with an average age of 62<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14 years&#46; The average follow-up time was 25<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19 months&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Six patients had prior oncological history &#40;and were in complete clinical remission&#41; at the time of the PET-CT request&#46; These included cases of Hodgkin&#39;s lymphoma &#40;HL&#41;&#44; breast cancer&#44; uterine cancer&#44; rectal cancer and two cases of prostate cancer&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">In ten patients the final diagnosis of neoplasia was confirmed&#44; constituting the final NPS group&#46; Seven corresponded to invasive neoplasia and the remaining three were confirmed as a high-grade dysplasia of the cervix&#44; an <span class="elsevierStyleItalic">in situ</span> cervical carcinoma and a mature ovarian teratoma&#46; In <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> patient characteristics are listed&#46; Excluding the three non-invasive cancer cases&#44; PET-CT was helpful in locating malignancy in 5 of 7 patients&#44; representing a sensitivity of 71&#37;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0140" class="elsevierStylePara elsevierViewall">After the removal of the primary tumour&#44; symptoms persisted in 3 cases&#58; sensory polyneuropathy of the lower limbs in the patient with <span class="elsevierStyleItalic">in situ</span> cervical cancer&#44; cerebellar syndrome in the patient with relapsed HL &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41; and limbic encephalitis in a patient with SCLC &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Three patients died &#40;recurrence of breast cancer and prostate cancer and one patient with SCLC&#41;&#46; In the remaining cases neurological symptoms disappeared after removal of the primary tumour&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">Eight patients had positive results for onconeural antibodies&#46; Four of these belonged to the group of patients finally diagnosed with neoplastic syndrome&#44; detailed in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46; The other four cases&#44; all with negative PET-CT&#44; corresponded to&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0150" class="elsevierStylePara elsevierViewall">Patient with a history of prostate cancer undergoing androgen deprivation therapy in remission &#40;undetectable PSA&#41; with CS and positive for Ma2&#47;Ta&#46; This patient has had 2 negative PET-CT results&#44; and is being treated with immunotherapy responding partially&#46; The origin of the neoplasia is undiagnosed&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0155" class="elsevierStylePara elsevierViewall">NCS patient&#44; positive for amphiphysin antibodies&#44; unidentified origin of the neoplastic process and partial response to treatment with immunotherapy&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0160" class="elsevierStylePara elsevierViewall">Two patients with NCS positive for anti-HU&#46; Both catalogued with polyneuropathy of unknown origin&#44; and neoplastic process was not determined during follow-up&#46;</p></li></ul></p><p id="par0165" class="elsevierStylePara elsevierViewall">In 35 patients antibody determination was not performed and in 21 patients results were negative&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">The syndromes of patients analysed were classified as CS in nineteen cases &#40;30&#37;&#41; and NCS in twenty-seven &#40;42&#37;&#41; cases&#46; Eighteen cases &#40;28&#37;&#41; did not fit either NCS or CS definitions&#44; so were labelled unclassifiable&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Ten &#40;16&#37;&#41; cases were confirmed as definite NPS&#44; thirteen &#40;20&#37;&#41; cases classified as possible NPS&#44; and the remaining cases were considered unclassifiable&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">PET-CT was classified as positive in seven of ten &#40;70&#37;&#41; patients with definite NPS&#46; PET-CT was positive in only two patients &#40;15&#37;&#41; with possible NPS and normal in eleven &#40;85&#37;&#41; patients with possible NPS&#46; <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> details the results&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0185" class="elsevierStylePara elsevierViewall">Statistical analysis of the results found a significant relationship &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; between the clinical classification of NPS &#40;SC <span class="elsevierStyleItalic">vs&#46;</span> SNC&#41; and the final diagnosis &#40;definite NPS <span class="elsevierStyleItalic">vs</span> possible&#41;&#46; SC patients were more likely to be associated with final NPS than those with NCS &#40;38&#37; <span class="elsevierStyleItalic">vs</span> 16&#37;&#41;&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">We also found that most of the cases classified as NCS &#40;18&#59; 72&#37;&#41; and all the clinically unclassifiable cases &#40;16&#59; 100&#37;&#41; did not fit either of the final diagnostic categories &#40;definite NPS <span class="elsevierStyleItalic">vs</span> possible&#41;&#46; That is to say&#44; cases with very low clinical suspicion of NPS were associated with other final diagnoses unrelated to this entity&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">76&#46;2&#37; of patients with negative PET-CT had negative results for onconeuronal antibodies &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">There was no statistical significance between the final diagnosis of the syndrome &#40;definite NPS <span class="elsevierStyleItalic">vs</span> possible&#41; after follow-up and the results of the PET-CT &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;08&#41;&#44; although we noted that there were a higher proportion of positive studies PET-CT in patients with definite NPS and more negative studies in the NPS possible cases&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Two positive PET-CTs with findings corresponding to suspect malignancy&#44; were due to mesenteric nodules and were finally classified as lymphadenitis&#46; They corresponded to a patient with rectal cancer&#44; with no locally affected lymph nodes&#44; and a suspected lesion in the <span class="elsevierStyleItalic">rectal ampulla</span> as shown on the PET-CT &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41; and another patient without proven malignancy who was eventually diagnosed with Parkinson-plus syndrome&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0210" class="elsevierStylePara elsevierViewall">The remaining sixteen of the cases with doubtful PET findings were&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0215" class="elsevierStylePara elsevierViewall">Pseudonodular breast lesion with moderate metabolism associated in the patient with <span class="elsevierStyleItalic">in situ</span> cervical carcinoma&#46; The mammography was normal&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">-</span><p id="par0220" class="elsevierStylePara elsevierViewall">Three cases of thyroid nodules with detected metabolism&#46; No biopsy was performed in two of the cases&#44; and the third died&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">-</span><p id="par0225" class="elsevierStylePara elsevierViewall">Nonspecific mediastinal adenopathy with&#47;without associated lung lesions in eight cases&#46; The lung lesions consisted of infiltrates or pseudonodules in three cases&#46; Complementary imaging tests did not suggest the need for biopsies&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">-</span><p id="par0230" class="elsevierStylePara elsevierViewall">Other adenopathies included&#58; two laterocervical&#44; one supradiaphragmatic and one infradiaphragmatic with low metabolism&#46; Findings were not suspected of malignancy and therefore not recommended for biopsy&#46;</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">-</span><p id="par0235" class="elsevierStylePara elsevierViewall">Nodular&#47;pseudonodular lung lesions with detectable metabolism&#46; They corresponded to a patient with a previous pneumonia months before the PET-CT and therefore were suggestive of residual inflammatory processes&#46; The patient died in the following months without a definitive diagnosis being established&#46;</p></li></ul></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0240" class="elsevierStylePara elsevierViewall">Signs and symptoms resulting from damage to any part of the nervous system through immunological means&#44; and neoplastic aetiology are what are called NPS&#46; The symptoms usually present at a distance from the primary tumour or metastasis and often precede&#44; by years&#44; the clinical underlying manifestations of the neoplastic process&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">10</span></a></p><p id="par0245" class="elsevierStylePara elsevierViewall">The response to the onconeural antigens is the production of anti-neuronal antibodies which can cross the blood brain barrier and attack the central or peripheral nervous system&#46; These antibodies can be detected in blood plasma or cerebrospinal fluid&#46; However&#44; only a minority of the patients with these antibodies present neurological symptoms&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">12</span></a></p><p id="par0250" class="elsevierStylePara elsevierViewall">In approximately 60&#37; of patients with NPS&#44; highly specific onconeural antibodies are found&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">13</span></a> However&#44; although some of these antibodies are present more frequently in certain tumours&#44; their detection is neither sensitive nor specific enough for diagnosis&#46; This means that not all NPS will imply positivity for onconeural antibodies&#44; and not all patients with positive antibodies will have NPS&#46; In fact&#44; not all the patients who present onconeural antibodies are diagnosed with malignant disease or have tumours detected in autopsy&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">6&#44;14&#44;15</span></a></p><p id="par0255" class="elsevierStylePara elsevierViewall">The diagnostic sensibility of PET in NPS is between 75&#37; and 100&#37;&#46; In <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a> an overview of the main studies is shown&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0260" class="elsevierStylePara elsevierViewall">The percentage of positivity for anti-neuronal antibodies in studies which have used metabolic imaging looking for malignancy is variable&#44; between 10&#37; and 53&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">7&#44;9</span></a> In this study eight of the twenty-nine patients for whom onconeural antibody tests were requested were positive&#59; the true utility of this parameter in our population is unknown&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">Previous studies have shown a relationship between the presence of onconeural antibodies and a positive PET result&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">6&#44;16&#44;17</span></a> For this reason&#44; given the possible influence of the positivity of the onconeural antibodies in the PET results&#44; some authors have recommended the use of FGD-PET-CT in cases of high clinical suspicion&#44; and well characterised antibodies&#46; Mckeon et al&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">5</span></a> found a statistically significant association between the presence of antibodies and successful localisation of neoplasia with PET&#58; 70&#37; of patients with cancer came up positive for antibodies&#44; and only 14&#37; of patients without cancer&#46; Rees el al&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">4</span></a> found positivity for antibodies in 43&#37; of positive PET cases&#44; compared with 16&#37; of negative PET cases&#44; although the differences were not statistically significant&#46; In our study&#44; 76&#37; of patients negative for onconeural antibodies had a negative FDG-PET-CT &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;36&#41; although the reduced number of cases limits the reliability of drawn conclusions&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">On one hand&#44; the dilemma remains regarding the treatment of patients positive for onconeural antibodies yet no neoplasia was detected in PET&#46; Patel et al&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">6</span></a> found that in 63 of 73 patients positive for antibodies and negative PET&#44; there was no neoplasia found after extensive study and follow-up&#44; leading to the hypothesis that the very same antibodies had actually led to the destruction of the tumour&#44; either that or the tumour was so small it was undetectable&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">10</span></a> In 2006 the Paraneoplastic Neurological Syndrome Euronetwork recommended a five-year follow-up period before declaring absence of occult malignancy in a patient&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">18</span></a> Regarding period of control in cases positive for antibodies where no neoplasia was detected&#44; the European Federation of Neurological Societies recommends repeating screening tests every six months for four years&#44; except in cases of Lambert&#8211;Eaton myasthenic syndrome &#40;LEMS&#41; in which two years would be sufficient&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">19</span></a></p><p id="par0275" class="elsevierStylePara elsevierViewall">Some authors define PET as the best technique available&#44; although the guides do not mention PET during follow-up&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">16</span></a></p><p id="par0280" class="elsevierStylePara elsevierViewall">On the other hand&#44; patients may well have NPS without onconeural antibodies&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">10</span></a> Hadjivassiliou et al&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">8</span></a> mention in their study that only 50&#37; of patients with malignant disease&#44; as proven by biopsy&#44; were positive for onconeural antibodies&#46; In these cases&#44; metabolic imaging has resulted superior to conventional images&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">4&#44;6&#44;16&#44;17&#44;20</span></a> That is why the European Federation of Neurological Societies recommends PET when morphological imaging tests come up negative&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">19</span></a> However&#44; it seems that this diagnostic sequence&#44; given the hybrid character of PET-CT is not strictly necessary&#46; Schramm et al&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">21</span></a> in a cohort study of patients with NPS found that PET-CT with intravenous contrast showed higher sensitivity and specificity than the CT with contrast alone &#40;100&#37; and 90&#37; <span class="elsevierStyleItalic">vs</span> 78&#37; and 88&#37;&#41;&#46; In our sample of patients finally diagnosed with a tumour&#44; two were negative for antibodies&#44; and in four cases they did not undergo the antibody test &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><p id="par0285" class="elsevierStylePara elsevierViewall">So&#44; although the presence of onconeural antibodies should not be a requisite for the realisation of PET in NPS&#44; the serological evidence of these antibodies may be of use in improving the diagnostic performance of PET&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">8</span></a></p><p id="par0290" class="elsevierStylePara elsevierViewall">SCLS constitutes one of the principal causes of NPS&#46; In cases of positivity for the anti-Hu antibody associated with the paraneoplastic syndrome&#44; the metastases of SCLC are often limited to the mediastinum&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">21</span></a> In a study including patients positive for onconeuronal antibodies&#44; 80&#37; of the patients with SCLC were found to have central mediastinal tumours&#46; In these cases&#44; PET was positive in 100&#37; of the cases&#44; while sensitivity of CT was 50&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">22</span></a> In our sample PET-CT detected mediastinal adenopathy with pathological metabolism in the two cases of SCLC&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall">Regarding the clinical characteristics of NPS&#44; very few published works have analysed the character of the neurological symptomology in order to categorise the syndrome as either CS or NCS&#46; The percentage of patients with NPS categorised as CS is variable&#44; and ranges between 37&#37; and 62&#37; in studies which have used metabolic images&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">7&#44;9</span></a> Previous studies have documented a different diagnostic performance of PET when considering the presence of CS or not&#44; finding higher rates of abnormal PET in patients with CS &#40;41&#37;&#41; than patients with NCS &#40;21&#37;&#41;&#59; concluding that PET performs better in classical paraneoplastic syndromes&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">8</span></a> In our study&#44; classifying the patients as definite or possible NPS&#44; we found that 60&#37; of the definite NPSs had a positive PET-CT and 85&#37; of the possible NPSs had a negative PET-CT &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;08&#41;&#46;</p><p id="par0300" class="elsevierStylePara elsevierViewall">Regarding false positives &#40;FP&#41; in PET&#44; the prevalence seems high&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">6</span></a> The fact that in many cases the tumours associated with NPS are small &#8211; often with only lymph node metastases &#8211; means that the study must be more exhaustive&#44; unfortunately increasing the FP rate&#46; Given the poor specificity of PET&#44; the correct classification of some lesions with positive metabolism is difficult&#46; In our sample eighteen studies had doubtful results&#44; in the end classified as FP&#44; with adenopathy being the most prevalent type&#46; In three cases&#44; patients presented thyroid nodules with increased metabolism&#46; Similar findings have also been reported previously&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">5</span></a></p><p id="par0305" class="elsevierStylePara elsevierViewall">As regards false negative results&#44; Patel et al&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">6</span></a> found that PET was unable to detect malignancy in two cases of neoplasia of gynaecological origin&#46; In our study&#44; we also had limited ability to detect the three cases of gynaecological disease&#46; The fact that two of these cases corresponded to non-invasive tumours and the third was a non-malignant mature teratoma&#44; we think explains the lack of metabolic detectability&#59; however&#44; we decided to include them as false negative PET-CT&#46; In the case of the teratoma&#44; the patient had onconeural antibodies against the N-methyl-<span class="elsevierStyleSmallCaps">d</span>-aspartate receptor&#46; The symptoms of encephalitis disappeared after the removal of the tumour and the patient remained asymptomatic during the follow-up period&#46; Although not part of the objectives of this study&#44; it was interesting to see that encephalitis caused by anti-N-methyl-<span class="elsevierStyleSmallCaps">d</span>-aspartate receptor onconeuronal antibodies can be associated with cerebral hypo-metabolism&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">23</span></a></p><p id="par0310" class="elsevierStylePara elsevierViewall">Concerning limitations&#44; the low prevalence of malignancy in our sample of patients led to a more effective analysis of the diagnostic performance of PET-CT&#46; This issue has meant that authors have referred to the PET-CT as over-valued regarding to its role in the detection of occult neoplasia in patients with NPS&#46; <a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">7</span></a>These authors suggest that PET-CT be reserved only for patients with high index of clinical suspicion of NPS and after negative conventional imaging studies&#46; However these authors studied a limited sample of patients&#44; with low prevalence of malignancy&#46; Our detectability rate coincided with those of previous authors&#44; if we take into account the sample of patients finally diagnosed with invasive cancers&#46; In sight of these results&#44; we think that a more careful selection of patients would lead to a higher detectability of malignancy rate&#44; a reduction in false positives&#44; and therefore the optimisation of PET-CT use&#46;</p><p id="par0315" class="elsevierStylePara elsevierViewall">Furthermore&#44; the limited knowledge of the state of onconeural antibodies&#44; and the low prevalence of positivity probably limited the ability to find associations with PET-CT results&#46;</p><p id="par0320" class="elsevierStylePara elsevierViewall">The reduced follow-up period could have led to false diagnosis if the patient was still developing a potentially detectable malignancy&#44; a process which can last up to five years after the appearance of neurological symptoms&#46; However&#44; in spite of its relevance&#44; we do not think this fact conditioned the final diagnostic result of our patient sample significantly&#44; given the lack of positive onconeural antibody results in some cases and that many of these syndromes did not correspond to CS&#44; which reduces the probability that they originated from a neoplastic process&#46; Equally the fact that patients with previously known neoplasia were included in the study&#44; even in clinical remission&#44; could have conditioned some of the results&#44; especially because the set remission period &#40;6 months&#41; may not have been enough&#46;</p><p id="par0325" class="elsevierStylePara elsevierViewall">Considering the strong points&#44; this study analysed a considerable sample of patients with clinical suspicion of NPS&#46; They were categorised as either CS or NCS&#44; and studied with the onconeural antibody results in order to try to define the implications of these variables in the results of PET-CT&#44; and in the establishment of the neoplastic origin of the syndrome&#46; We consider these circumstances&#44; seen in very few studies so far as fundamental for the correct determination of diagnostic performance in PET-CT&#46;</p><p id="par0330" class="elsevierStylePara elsevierViewall">Moreover&#44; the results of our study&#44; in spite of the low prevalence&#44; of invasive type malignance &#40;11&#37;&#41;&#44; reflect the potential of <span class="elsevierStyleSup">18</span>FDG-PET-CT in the evaluation of patients with suspected NPS at a sensitivity of 71&#37;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conclusion</span><p id="par0335" class="elsevierStylePara elsevierViewall">In spite of low prevalence of malignancy in our series&#44; PET-CT detected malignancy in a significant proportion of patients with invasive cancer&#46;</p><p id="par0340" class="elsevierStylePara elsevierViewall">The presence of anti-onconeural antibodies and the clinical characteristics of NPS seem to be relevant conditions for the diagnostic indication of PET-CT with <span class="elsevierStyleSup">18</span>F-FDG&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflict of interest</span><p id="par0345" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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          "identificador" => "sec0045"
          "titulo" => "Conflict of interest"
        ]
        10 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2014-12-11"
    "fechaAceptado" => "2015-02-27"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec546672"
          "palabras" => array:4 [
            0 => "Paraneoplastic neurological syndrome"
            1 => "Clinical classification"
            2 => "PET&#47;CT"
            3 => "<span class="elsevierStyleSup">18</span>F-FDG"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec546671"
          "palabras" => array:4 [
            0 => "S&#237;ndrome paraneopl&#225;sico neurol&#243;gico"
            1 => "Clasificaci&#243;n cl&#237;nica"
            2 => "PET&#47;TC"
            3 => "<span class="elsevierStyleSup">18</span>F-FDG"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">This study aimed to determine the diagnostic impact of <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT based on the clinical features of paraneoplastic neurological syndrome &#40;PNS&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Multicenter retrospective and longitudinal study of patients with suspicion of PNS&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The clinical picture was classified into classic &#40;CS&#41; and non-classic syndrome &#40;NCS&#41;&#46; After the follow-up&#44; the definitive or possible diagnosis of PNS was established&#46; The pictures that did not match any of the previous criteria were categorised as non-classifiable&#46; The state of the onconeural antibodies was studied&#46;</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The PET&#47;CT was classified as positive or negative for the detection of malignancy&#46; The relationship between PET&#47;CT findings and the final diagnosis was determined&#46; The differences between variables &#40;Pearson test <span class="elsevierStyleItalic">X</span><span class="elsevierStyleSup">2</span>&#41; and the relationship between the results of the PET&#47;CT and the final diagnosis was analysed&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A total of 64 patients were analysed&#44; classifying 30&#37; as CS and 42&#37; as NCS&#46; After the follow-up&#44; 20&#37; and 16&#37; of subjects were diagnosed as possible and definitive PNS&#44; respectively&#46; Positive onconeural antibodies were found in 13&#37; of the patients&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A definitive diagnosis of PNS was associated with a positive PET&#47;CT &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;08&#41;&#46; A significant relation between antibodies expression and final diagnosis of neoplasia &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;04&#41; was demonstrated&#46;</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">The PET&#47;CT correctly localised malignancy in 5&#47;7 cases of invasive cancer&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">The PET&#47;CT showed a higher percentage of positive results in patients with definitive diagnosis of PNS&#46; Despite the low prevalence of malignancy in our series&#44; the PET&#47;CT detected malignancy in a significant proportion of patients with invasive cancer&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objective"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Material 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">Objetivo</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Definir el impacto diagn&#243;stico de la PET&#47;TC con <span class="elsevierStyleSup">18</span>F-FDG en funci&#243;n de las caracter&#237;sticas cl&#237;nicas del s&#237;ndrome paraneopl&#225;sico neurol&#243;gico &#40;SPN&#41;&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todos</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Estudio retrospectivo multic&#233;ntrico y longitudinal de pacientes con sospecha de SPN&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">El cuadro cl&#237;nico se clasific&#243; en s&#237;ndrome cl&#225;sico &#40;SC&#41; o no cl&#225;sico &#40;SNC&#41;&#46; Tras el seguimiento se estableci&#243; el diagn&#243;stico de SPN definitivo o posible&#46; Los cuadros que no encajaron en ninguna de las categor&#237;as previas se catalogaron como no clasificables&#46; Se analiz&#243; el estado de los anticuerpos onconeuronales&#46;</p><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">La PET&#47;TC se clasific&#243; en positiva o negativa para la detecci&#243;n de malignidad&#46; Se determin&#243; la relaci&#243;n entre los hallazgos PET&#47;TC y el diagn&#243;stico final&#46; Se analizaron las diferencias entre variables &#40;Chi cuadrado de Pearson&#41; y la relaci&#243;n entre el resultado de la PET&#47;TC y el diagn&#243;stico definitivo&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Se analizaron 64 pacientes&#46; El 30&#37; de los cuadros cl&#237;nicos se catalogaron como SC y el 42&#37; como SNC&#46; Tras el seguimiento el 20&#37; se clasific&#243; en SPN posible y el 16&#37; en definitivo&#46; El 13&#37; de los pacientes ten&#237;a anticuerpos onconeuronales positivos&#46;</p><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">El hecho de poseer un SPN definitivo se relacion&#243; con un resultado positivo de la PET&#47;TC &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;08&#41;&#46; Se demostr&#243; relaci&#243;n significativa entre la positividad de los anticuerpos y el diagn&#243;stico final de proceso neopl&#225;sico &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;04&#41;&#46;</p><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">La PET&#47;TC fue eficaz en la correcta localizaci&#243;n tumoral en 5&#47;7 casos con c&#225;ncer invasivo&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">La PET-TC mostr&#243; un mayor porcentaje de resultados positivos en pacientes con diagn&#243;stico de SPN definitivo&#46; A pesar de la baja prevalencia de malignidad en nuestra serie&#44; la PET&#47;TC detect&#243; malignidad en una significativa proporci&#243;n de pacientes con c&#225;ncer invasivo&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Objetivo"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Material y m&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as&#58; Garc&#237;a Vicente AM&#44; Vega Caicedo CH&#44; Mond&#233;jar Sol&#237;s R&#44; de Ayala Fern&#225;ndez JA&#44; Garrido Robles JA&#44; Pena Pardo FJ&#44; et al&#46; PET&#47;TC con <span class="elsevierStyleSup">18</span>F-FDG en la valoraci&#243;n de pacientes con sospecha de s&#237;ndrome paraneopl&#225;sico neurol&#243;gico&#46; Rev Esp Med Nucl Imagen Mol&#46; 2015&#59;34&#58;236&#8211;243&#46;</p>"
      ]
    ]
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        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Patient with a history of Hodgkin&#39;s lymphoma&#44; in complete remission presenting cerebellar syndrome and therefore suspected NPS&#46; Previous MRI showed unspecific signs in L2&#46; The PET-CT showed bilateral hypermetabolic laterocervical adenopathy and a hypermetabolic lesion in L2 which did not show on previous PET-CT scans&#44; suggesting infiltration&#46; Diagnosis of recurrent tumour was confirmed&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
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          "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Patient with limbic encephalitis&#44; positive for onconeural antibodies &#40;amphiphysin&#41;&#46; Previous CT study produced inconclusive findings&#46; In the PET-CT hypermetabolic adenopathy in the aortopulmonary window and ipsilateral hilum was observed&#46; Pathology report confirmed SCLC&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Figure 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
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        "figura" => array:1 [
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        "descripcion" => array:1 [
          "en" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Patient with CS and positive for neuron-specific enolase&#46; PET-CT shows hypermetabolic mesenteric nodules and a doubtful lesion in the rectal ampulla &#40;perhaps due to physiological elimination&#44; presence of faeces&#41;&#46; The final diagnosis was pT1N0 rectal cancer&#46; The findings in the mesentery were catalogued as mesenteric lymphadenitis&#46;</p>"
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      ]
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        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "fuente" => "<span class="elsevierStyleItalic">Source</span>&#58; Graus et al&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">10</span></a>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Syndromes of the central nervous system</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Classical</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Encephalomyelitis<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Limbic encephalitis<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Sub-acute cerebellar degeneration<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Opsoclonus myoclonus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Non-classical</span>Brainstem encephalitisStiff person syndromeOptic neuritisCancer associated retinopathyNecrotising myelopathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Syndromes of the peripheral nervous system</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Classical</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Sub-acute sensory neuronopathy<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Chronic gastrointestinal pseudo-obstruction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Non-classical</span>Guillain-Barr&#233; syndromeBrachial neuritisAcute pandysautonomiaNeuropathy with vasculitisNeuropathy and paraproteinaemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Syndromes of the neuromuscular junction and muscle</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Classical</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Lambert-Eaton myasthenic syndrome<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Dermatomyositis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Non-classical</span>Myasthenia gravisAcquired neuromyotoniaAcute necrotising myopathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab848262.png"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Classical and non-classical paraneoplastic neurological syndromes according to Graus et al&#46;</p>"
        ]
      ]
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        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "fuente" => "<span class="elsevierStyleItalic">Source</span>&#58; Graus et al&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">10</span></a>"
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
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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"><span class="elsevierStyleItalic">Definite NPS</span>&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"><span class="elsevierStyleHsp" style=""></span>A classical syndrome and cancer&#44; with or without onconeural antibodies&#44; that develops within five years of the diagnosis of the neurological disorder&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"><span class="elsevierStyleHsp" style=""></span>A non-classical syndrome that resolves or significantly improves after cancer treatment without concomitant immunotherapy&#44; provided that the syndrome is not susceptible to spontaneous remission&#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"><span class="elsevierStyleHsp" style=""></span>A non-classical syndrome with onconeural antibodies &#40;well characterised or not&#41; and cancer that develops within five years of the diagnosis of the neurological disorder&#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"><span class="elsevierStyleHsp" style=""></span>A neurological syndrome &#40;classical or not&#41; with well characterised onconeural antibodies &#40;anti-Hu &#40;ANNA-1&#41;&#44; Yo &#40;CA-1&#41;&#44; CV2 &#40;CMPR5&#41;&#44; Ri &#40;ANNA-2&#41;&#44; Ma2&#44; or amphiphysin&#41;&#44; and no cancer&#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"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Possible NPS</span>&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"><span class="elsevierStyleHsp" style=""></span>A classical syndrome&#44; no onconeural antibodies&#44; no cancer but at high risk to have an underlying tumour &#40;for example heavy smoker or over 50 years of age&#41;&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"><span class="elsevierStyleHsp" style=""></span>A neurological syndrome &#40;classical or not&#41; with partially characterised onconeural antibodies and no cancer&#46;A non-classical syndrome&#44; no onconeural antibodies&#44; and cancer present within two years of diagnosis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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        "descripcion" => array:1 [
          "en" => "<p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Diagnostic criteria for paraneoplastic neurological syndromes according to Graus et al&#46;</p>"
        ]
      ]
      5 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0115" class="elsevierStyleSimplePara elsevierViewall">A&#58; age&#59; Ab&#58; antibodies&#59; CS&#58; classical syndrome&#59; F&#58; female&#59; FDG&#58; fluorodeoxyglucose&#59; M&#58; male&#59; NCS&#58; non-classical syndrome&#59; NR&#58; not requested&#59; NPS&#58; neurological paraneoplastic syndrome&#59; PET-CT&#58; positron emission tomography-computed tomography&#59; SCLC&#58; small cell lung cancer&#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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">G&#47;A &#40;yrs&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">NPS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Previous neoplasm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Onconeural Ab&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">FDG PET-CT findings&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Final diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">M&#47;64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hodgkin&#39;s lymphoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hypermetabolic supradiaphragmatic adenopathy and bone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Recurrent lymphoma&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">M&#47;70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NCS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prostate cancer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hypermetabolic inguinal adenopathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Recurrent prostate cancer&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">F&#47;61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Breast cancer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Anti-Yo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hypermetabolic inguinal adenopathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Recurrent breast cancer&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">F&#47;51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NCS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Pseudonodular breast lesion with moderate metabolism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">in situ</span> cervical carcinoma&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">M&#47;54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Normal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hypermetabolic mesenteric nodules&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rectal cancer&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">F&#47;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Anti-NMDA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Negative &#40;ametabolic cyst&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Mature ovarian teratoma&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">M&#47;81&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Amphiphysin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hypermetabolic mediastinal adenopathy and in pulmonary hilum&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">SCLC&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">M&#47;65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NCS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Normal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prostate cancer&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">F&#47;70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NCS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">High grade cervical dysplasia&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">M&#47;56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NCS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ANNA1-MAG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hypermetabolic mediastinal adenopathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">SCLC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab848258.png"
              ]
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">Results obtained in the 10 patients diagnosed with malignancy&#46;</p>"
        ]
      ]
      6 => array:7 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0125" class="elsevierStyleSimplePara elsevierViewall">Ab&#58; antibodies&#59; NPS&#58; neurological paraneoplastic syndrome&#59; PET-CT&#58; positron emission tomography-computed tomography&#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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variables&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Positive PET-CT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Negative PET-CT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Onconeural Ab</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4 &#40;50&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4 &#40;50&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;36&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"><span class="elsevierStyleHsp" style=""></span>Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;24&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16 &#40;76&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">NPS</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Definite&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6 &#40;60&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4 &#40;40&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;08&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"><span class="elsevierStyleHsp" style=""></span>Possible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;15&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11 &#40;85&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => "xTab848259.png"
              ]
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          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Unreported cases correspond to unclassifiable syndromes&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0120" class="elsevierStyleSimplePara elsevierViewall">Relationship between the clinical variables and the PET-CT results&#46;</p>"
        ]
      ]
      7 => array:7 [
        "identificador" => "tbl0025"
        "etiqueta" => "Table 5"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0135" class="elsevierStyleSimplePara elsevierViewall">mod GC&#58; modified gamma camera&#59; <span class="elsevierStyleItalic">N</span>&#58; number of patients&#59; NPS&#58; neurological paraneoplastic syndrome&#59; P&#58; prospective study&#59; PET-CT&#58; positron emission tomography-computed tomography&#59; R&#58; retrospective study&#59; Se&#58; sensitivity&#59; CTivc&#58; computed tomography with intravenous contrast&#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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Author&#44; year&#44; study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Methodology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PET positive&#59; Se&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Malignancy<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Antoine&#44; 2000&#44; R<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">17</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PET&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#59; 100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&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">Rees&#44; 2001&#44; R<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">4</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PET&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16&#59; 88&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&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">Berner&#44; 2003&#44; R<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">24</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PET&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#59; 86&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&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">Younes-Mhenni&#44; 2004&#44; P<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">16</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PET&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&#59; 83&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&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">Linke&#44; 2004&#44; R<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">20</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PET&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&#44; 90&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&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">Patel&#44; 2008&#44; R<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">6</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">107&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PET&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24&#59; 80&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&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">Hadjivassiliou&#44; 2009&#44; P<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">8</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">mod GC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&#59; 75&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&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">Bannas&#44; 2010&#44; R<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">7</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PET-CT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#59; 100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&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">Mc Keon&#44; 2010&#44; R<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">5</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">56&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Matsuhisa&#44; 2012&#44; R<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">25</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&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">Vaidyanathan&#44; 2012&#44; R<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">9</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">68&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&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">Schramm&#44; 2013&#44; R<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">66&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&nbsp;\t\t\t\t\t\t\n
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Article information

ISSN: 22538089
Original language: English

DOI:10.1016/j.remnie.2015.05.013

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