Histologic study of the effects of chemoembolization with preloaded doxorubicin beads in patients with hepatocellular carcinoma

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Hepatocarcinoma en el segmento 8, de 50mm y áreas de necrosis (flecha). b) Angiografía hepática que confirma el tumor hipervascularizado y otro adyacente hipovascular de 9mm (flecha), no detectado con la TC. c) Tras dos sesiones de quimioembolización transarterial selectiva con microesferas de hidrogel precargadas con doxorrubicina (QETA-DEB) selectiva la respuesta del tumor es completa. d) Hígado explantado a los 9 meses de la última sesión de QETA-DEB. Solo se observa necrosis parcial (30%) del tumor (N) con áreas periféricas de tumor viable (★). Obsérvense las microesferas (flecha) en la proximidad del tumor. e) Imagen microscópica (H&E 10x) del tumor de mayor tamaño en la que se aprecian áreas de necrosis (N) y de viabilidad tumoral (T). f) Imagen microscópica del tumor hipovascular de menor tamaño (H&E 10x). Viabilidad tumoral completa (T) a pesar de que hay microesferas en el lecho tumoral (cabeza de flecha)." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "L.J. 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Zurera, J.J. Espejo, S. Lombardo, T. Marchal, M.C. Muñoz, M. Canis, J.L. Montero" "autores" => array:7 [ 0 => array:4 [ "nombre" => "L.J." "apellidos" => "Zurera" "email" => array:1 [ 0 => "lzurera61@gamil.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "J.J." "apellidos" => "Espejo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "S." "apellidos" => "Lombardo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "T." "apellidos" => "Marchal" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "M.C." "apellidos" => "Muñoz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 5 => array:3 [ "nombre" => "M." "apellidos" => "Canis" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "J.L." "apellidos" => "Montero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Unidad de Radiología Intervencionista, Hospital Universitario Reina Sofía, Córdoba, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Anatomía Patológica, Hospital Universitario Reina Sofía, Córdoba, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "IMIBIC, Hospital Universitario Reina Sofía, Córdoba, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Unidad de Hepatología, Hospital Universitario Reina Sofía, Córdoba, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Estudio histológico sobre el efecto de la quimioembolización con partículas precargadas con doxorrubicina en el hepatocarcinoma" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1350 "Ancho" => 1800 "Tamanyo" => 319647 ] ] "descripcion" => array:1 [ "en" => "(a and b) Axial T1-weighted MRIs after the injection of gadolinium (artery phase). Three (3) 30, 20 and 20mm-hepatocarcinomas (arrows) can be seen. (c) Hepatic angiography (late phase) showing the tumors (arrows). (d) and (e) T1-weighted MRI axial images after the injection of gadolinium (artery phase). Partial response after one session of selective transarterial chemoembolizations with preloaded selective doxorubicin hydrogel beads (DEB-TACE) in the three (3) hepatocarcinomas (arrows) whose size has been reduced but have been enhanced peripherally. (f) Microscopic image (H&E 10×) of one of those tumors 10 months after DEB-TACE. Central necrosis (N) of 70% with a peripheral halo of tumor feasibility (♦)." ] ] ] "textoCompleto" => "IntroductionTransarterial chemoembolization (TACE) is a palliative treatment for patients with asymptomatic hepatocellular carcinoma (HCC), preserved liver function and lack of extrahepatic dissemination or vascular invasion (intermediate stage-B–based on the criteria from the Barcelona Clinic Liver Diseases–BCLC). Indications now include patients with early-stage HCC (Barcelona Clinic Liver Diseases–A) without surgical indication or local ablative therapies, to patients waiting for liver transplantation (LT) (in an effort to attain local control in the meantime) or to downstage the tumor in patients who exceed the criteria for LT.<a class="elsevierStyleCrossRefs" href="#bib0145">1,2</a>Not too long ago TACE started being used with preloaded doxorubicin hydrogel beads (DEB-TACE) that are better tolerated than conventional TACE (cTACE) with lipiodol+a chemotherapeutic agent+embolization particles (gelfoam or polyvinyl alcohol) since they release the drug in the liver blood stream more slowly and continually at the same time they reduce its passage into the systemic circulation (yet despite the fact that they increases the dose).<a class="elsevierStyleCrossRefs" href="#bib0155">3,4</a> Also it is more effective than conventional TACE in patients with recurrent and bilobar disease, although it is not been confirmed to improve survival or reduce local relapse.<a class="elsevierStyleCrossRefs" href="#bib0165">5,6</a> Nonetheless it does improve local response with respect to soft embolization–only embolization particles only.<a class="elsevierStyleCrossRef" href="#bib0175">7</a>The effect of TACE in HCC is necrosis that is evaluated through the imaging criteria of the European Association for the Study of the Liver.<a class="elsevierStyleCrossRefs" href="#bib0180">8–10</a> An acceptable anatomo-pathologic correlation has been observed<a class="elsevierStyleCrossRefs" href="#bib0195">11–14</a> in studies performed on transplanted livers after cTACE.<a class="elsevierStyleCrossRefs" href="#bib0215">15–17</a> However, the studies of anatomo-pathologic correlation of the antitumor effect of DEB-TACE<a class="elsevierStyleCrossRef" href="#bib0230">18</a> and the driving factors are scarce.Our goal is to assess the degree of actual tumor necrosis caused by DEB-TACE and those factors it possibly correlates to based on the anatomo-pathologic examination of the livers explanted in the LT.Material and methodsPatientsFrom 2008 until April 2012, we performed DEB-TACE in 120 cirrhotic patients with HCC of whom 21 were subsequently transplanted and then made up the sample of this retrospective study approved by the hospital ethics committee with the signing of the written informed consent to undergo the procedure. Given that for the LT, the Milan<a class="elsevierStyleCrossRef" href="#bib0145">1</a> criteria were followed, for the DEB-TACE the following criteria were included: (1) single tumor ≤5cm that cannot be treated through local ablative therapies; (2) up to three tumors none of them >3cm; (3) lack of vascular invasion or extrahepatic dissemination through imaging methods; (4) preserved liver function (child A–B); (5) acceptable coagulation condition (prothrombin activity>55%; platelets>60,000/mm3); (6) adequate kidney function (creatinine<1.5mg/dl); and (7) patients exceeding the Milan criteria (n=6) who were not initial candidates to undergo LT underwent DEB-TACE which led to tumor regression or downstaging were included in the waiting list.The exclusion criteria were: (1) portal thrombosis (total or partial); (2) significant hepatofugous portal flow in the angiography; (3) contraindication of doxorubicin; and (4) biliary obstruction.The diagnosis of HCC was achieved through different image modalitiesand pieces of equipment (because of our patients’ heterogeneity) and based on the criteria set by the clinical guidelines of the American Association for the Study of the Liver Diseases<a class="elsevierStyleCrossRefs" href="#bib0180">8,19</a> so the nodes were not biopsied yet six of them with atypical radiological behavior were tagged as HCC and then confirmed in an anatomo-pathological analysis.Angiographic proceedingThe right femoral artery was canalized, after anesthetizing the area locally and with the patient under sedation (1cc of fentanyl and 2cc of midazolam) so that a standard introducer (5F and 10cm long) could be introduced. We selectively catheterized the celiac trunk and the superior mesenteric artery with multipurpose or cobra-type of catheters (4–5F) and after analyzing the arterial anatomic variables and verifying portal patency and its preferential hepatic flow, the segmental branches of each tumor were supraselectively catheterized with microcatheters (Progreat. Terumo, Leuven or Rapid Transit. Cordis, Miami, USA) to inject the hydrogel beads (DC Bead. Biocompatibles, UK) mixed with iodized contrast in a 1:1 ratio. These beads were preloaded with doxorubicin (75mg per vial) 12h before the procedure at the Pharmacy Service.We considered that the DEB-TACE was adequate when fluoroscopically we started seeing the reflux of the embolization material–even if we had not administered the entire particle load available. This is why we always start the procedure with a 300–500mμ vial followed by another of 500–700mμ and when tumor devascularization was not adequate yet we completed it with 400–500mμ beads (Embozene, Celonova Biosciences, Newman, USA).When the disease was bilobar, the supraselective procedure was performed in a single session.No antibiotics or anti-inflammatories were administered in a prophylactic, routine fashion and post-embolization syndrome–abdominal pain, low-grade fever, vomiting, asthenia, etc. was managed individually and symptom-based.Clinical-radiologic follow-upA strict clinical and analytical control was carried out (hemogram and hepatorenal function test: transaminase, bilirubin, alkaline phosphatase, gamma-GT, creatinine, urea) during the first week, and then a first dynamic liver CT was performed 1 month after the DEB-TACE with a 64-crown multidetector CT, VCT Light Speed, (GE Health Care, Milwaukee, Wi, USA). The images were interpreted by consensus among the radiologists involved in the study who measured the largest axis of the nodes detected and intra-tumor enhancement. The nodes detected in the explanted liver but remained undetected though images before the LT were considered «new onset» nodes. Applying the criteria from the European Association for the Study of the Liver,<a class="elsevierStyleCrossRefs" href="#bib0180">8,10</a> we did not perform a new DEB-TACE session when the response was complete but we did when it was partial. When in presence of disease progression the patient was removed from the LT waiting list as the possibility of performing a new session or administering Sorafenib was individually evaluated for every patient.After this first control and given the retrospective character of our study the follow-up of patients on the waiting list was very variable and not constant (with different image modalities and equipment since they came from different hospitals) and in some of them we did not have any image modalities after the initial CT a month after the DEB-TACE yet no patient was lost during the follow-up.Anatomopathologic studyOnce the LT was performed the anatomo-pathologist made 3–5mm-thick coronal cuts and then transversal cuts of the explanted liver and the sections were fixed with 4% formaldehyde (buffered at pH 7 and stabilized in methanol). One hepato-pathologist with more than 20 years of experience selected 2.2–0.3cm sections and the nodes in order to process soak them in a paraffin solution, cut them and dye them. In her report, she recorded macroscopic data of the explanted piece (number and size of the nodes, anatomo-pathologic type and capsular or vascular infiltration). She also performed the microscopic study of each HCC subjectively assessing the percentage of necrosis in each one. Based on former studies three groups were separated based on this percentage: >90%, 60–90% and <60%.<a class="elsevierStyleCrossRefs" href="#bib0205">13,16</a>Statistical analysisFor the statistical analysis, the IBM software, PASW Statistics 18 (version in Spanish language) was used and the quantitative and qualitative variables were described. We compared the quantitative variables (pre- and post-DEB-TACE node size, number of nodes pre- and post-DEB-TACE and time elapsed from the last chemoembolization until the LT was performed) through the Kruskal–Wallis test and the Mann–Whitney U test. Qualitative variables (angiographic pattern, number of DEB-TACE and capsular/vascular infiltration of the HCC) with the Chi square test. The existing correlation between the nodes detected in the image and those found in the piece was established with Spearman's correlation ratio. Values were considered statistically significant when their level of reliability was beyond 95% (p<0.05).ResultsAmong the 21 patients studied, 18 were male with a mean age of 56 years (41–65 years). The cause of the cirrhosis was alcoholic (38%), hepatitis C virus (48%) or both (14%). Liver function was at a Child A (57%) and Child B (43%) stages. A DEB-TACE session was performed in 16 patients, two sessions in 3 patients and three sessions in two patients (mean: 1.3 sessions/patient). The mean time elapsed from the last session to the LT was 6 months (0.5–10.5 months) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>We detected (with a minimum of 2 coincidental image modalities) and treated 43 nodes with an average size of 25mm (8–55mm). Among them, 25 were classified subjectively as hypervascularized through image modalities, 12 were discreetly vascularized and 6 were avascular (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). In the piece 81 HCCs were found whose size was significantly reduced after the DEB-TACE (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>), with a overall average size of 15mm (8–70mm) (p<0.001), 17mm for the 43 detected through image modalities and 9mm for the 38 new-onset HCCs. Three (3) of the nodes disappeared, two (2) presented with vascular infiltration and two others with capsular infiltration. The median necrosis achieved after DEB-TACE was 39%, >90% in 21 HCCs, 60–90% in 7 and <60% in the remaining 53 (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>In 31 HCCs of 7 patients of the explanted piece, necrosis was nonexistent. Its mean size was 11mm, with an average 5 tumors/patient and a median time elapsed from the last session to the LT of 7.7 months. Among the 28 HCCs of the 16 patients where necrosis was >60%, the average size of the tumors was 20.5mm with an average 3.6 tumors/patient and a median time elapsed from the last session to the LT of 5.7 months.The statistical correlation between the index of necrosis and the time elapsed from the last DEB-TACE until the LT was high (p<0.001) and it became significantly smaller with the passing of time. This factor was related with the number of nodes found in the piece that also drove the necrosis in such a way that more tumors the smaller the necrosis (p<0.001) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). In 13 patients with ≤4 HCCs in the piece (23 nodes, 1.7 tumors/patient) the mean necrosis was 78%, while in 8 patients with >5 HCCs (56 tumors, 6.6 tumors/patient) it was just 20%. When we detected one or two nodes through image modalities the odds of having indexes of necrosis beyond 90% was greater (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).Neither the size of the nodes before the DEB-TACE (p=0.285) nor the number of procedures performed (p=0.158) influenced necrosis significantly (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>) (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia>In the 25 hypervascularized nodes (median size 25.6mm) the median necrosis was 70%, in the 12 hypervascularized tumors (median size 25.9mm), it as 46%, and in the 6 avascular tumors (median size 20.3mm), it was 50% but these differences were not statistically significant (p=0.387) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>) (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>).There was capsular and vascular infiltration in one patient in some of the nodes, in another patient just vascular infiltration and yet in another patient capsular infiltration only with an average 7.3 HCCs/patient. In the first two patients the median necrosis was nonexistent and in the third one it was 33%. Although tumor vascular infiltration did not significantly influence necrosis (p=0.112), the capsular infiltration did (p=0.024) (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>), yet these data are biased by the number of HCCs showing infiltration.<elsevierMultimedia ident="fig0015"></elsevierMultimedia>DiscussionIn this study we have analyzed the effect of DEB-TACE on HCCs with hydrogel beads loaded with 75mg of oral doxorubicin and saw that necrosis depends on the time elapsed until liver transplantation is performed, on the number of nodes in the piece and on the tumor capsular infiltration. The importance of these results is that there is one similar study published only<a class="elsevierStyleCrossRef" href="#bib0230">18</a> yet despite the fact that in many centers chemoembolization preloaded with particle has replaced both soft chemoembolization due to a better local response and conventional chemoembolization due to a better tolerance and response in advanced disease.<a class="elsevierStyleCrossRefs" href="#bib0155">3,7</a>The local response (degree of necrosis) to chemoembolization in patients with HCC is usually analyzed based oto radiologic criteria (mainly those of the European Association for the Study of the Liver). With conventional TACE the radiopathologic correlation of tumoral necrosis has been variable, with slightly more sensitivity of MR than CT,<a class="elsevierStyleCrossRefs" href="#bib0195">11,12</a> but it has not been studied much with DEB-TACE. In our study, we cannot correlate the local response of this modality with image modalities since they are not available on the days close to the transplant for many patients. However we can analyze factors that can possibly condition the necrosis caused by the particles. In our case one of the factors that influenced the necrosis the most was the time elapsed from the last treatment to the LT that is somehow related with the time on the waiting list. The longer the time the smaller the index of necrosis. As it has been described with the cTACE it was also related with the discordance between the number of tumors in the piece and those detected through image modalities and then treated supraselectively.<a class="elsevierStyleCrossRefs" href="#bib0200">12,15,20</a> Probably this is due to the fact that our patients on the LT waiting list are not followed up according to a protocol after their first liver CT (in an attempt to detecting new-onset untreated tumors) so in addition to a strict follow-up through image modalities we believe that repeated chemoembolization based on a protocol should be considered regardless the imaging response or in a lobar instead of a supra-selective fashion in order to operate on these new-onset tumors that are altering the desired antitumor effect. Similarly and just as it happens with the cTACE<a class="elsevierStyleCrossRefs" href="#bib0215">15,21</a> the smaller the number of nodes detected through image modalities the greater the overall necrosis in the piece.The correlation between the degree of necrosis attained with the cTACE and tumor size has been dissimilar. For some authors HCCs<2–3cm have better complete indexes of response<a class="elsevierStyleCrossRefs" href="#bib0200">12,22</a> but other results say otherwise<a class="elsevierStyleCrossRefs" href="#bib0255">23,24</a> and some other authors even defend the benefit of this modality to downstage tumors <5cm<a class="elsevierStyleCrossRef" href="#bib0265">25</a>. There is still little information about the DEB-TACE yet our results indicate that tumor size considered in isolation has little influence on necrosis somehow more driven by the other factors analyzed.Hypervascularization has been, in some cases, a factor independent from tumor necrosis when treated with cTACE<a class="elsevierStyleCrossRefs" href="#bib0200">12,15,26</a> but not in others.<a class="elsevierStyleCrossRef" href="#bib0275">27</a> Although we have not found any statistically significant relation there is a clear trend in our cases.Finally the tumor vascular and capsular infiltration is negatively correlated with the necrosis in HCC treated through cTACE and they are known factors of poor prognosis.<a class="elsevierStyleCrossRefs" href="#bib0200">12,15</a> Our results with DEB-TACE confirm that there is little necrosis in cases with capsular infiltration since they are closely related with tumor multiplicity being this trend similar to vascular infiltration which by the way does not achieve statistical significance probably because of the few tumors presenting with capsular infiltration.This study has its limitations especially those derived from its retrospective character and the small number of patients. Also the follow-up of the patients through image modalities has been irregular and inconsistent–non-protocolized due to the fact that our patients came from very different origins preventing the radio-pathologic correlation. Unlike other authors,<a class="elsevierStyleCrossRef" href="#bib0280">28</a> it has not been a goal of this paper to analyze survival and all those factors determining it.In sum the time elapsed from the last DEB-TACE session to the LV, the number and size of the tumors found in the piece and capsular infiltration are associated with the degree of necrosis, but neither the tumor vascularization pattern, the number of chemoembolization sessions or the size of tumors before the procedure had a strong influence. When one or two HCCs are found through image modalities, the odds of necrotizing are greater. Also the DEB-TACE can downstage the size and stage of HCC significantly.Ethical responsibilitiesProtection of people and animalsThe authors declare that no experiments with human beings or animals have been performed while conducting this investigation.Data confidentialityThe authors declare that in this article there are no data from patients.Right to privacy and informed consentThe authors declare that in this article there are no data from patients.Authors’ contributions<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">1.Manager of the integrity of the study: ZLJ, CM, MJL.</li><li class="elsevierStyleListItem" id="lsti0010">2.Study Idea: ZLJ, E JJ, CM, MJL.</li><li class="elsevierStyleListItem" id="lsti0015">3.Study Design: ZLJ, EJJ, CM, MJL, MMC.</li><li class="elsevierStyleListItem" id="lsti0020">4.Data Mining: ZLJ, EJJ, LS, CM, MJL.</li><li class="elsevierStyleListItem" id="lsti0025">5.Data Analysis and Interpretation: ZLJ, EJJ, LS, MT, MMC.</li><li class="elsevierStyleListItem" id="lsti0030">6.Statistical Analysis: ZLJ, MT.</li><li class="elsevierStyleListItem" id="lsti0035">7.Reference Search: ZLJ, EJJ, LS, MT, CM, MJL.</li><li class="elsevierStyleListItem" id="lsti0040">8.Writing: ZLJ, EJJ, LS, MMC.</li><li class="elsevierStyleListItem" id="lsti0045">9.Critical review of the manuscript with intellectually relevant remarks: ZLJ, EJJ, LS, MT, CM, MJL, MMC.</li><li class="elsevierStyleListItem" id="lsti0050">10.Approval of final version: ZLJ, EJJ, LS, MT, CM, MJL, MMC.</li></ul>Conflict of interestThe authors declare no conflict of interests." "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres566049" "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" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec583249" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres566050" "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" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec583248" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Angiographic proceeding" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Clinical-radiologic follow-up" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Anatomopathologic study" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0040" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0045" "titulo" => "Discussion" ] 8 => array:3 [ "identificador" => "sec0050" "titulo" => "Ethical responsibilities" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0055" "titulo" => "Protection of people and animals" ] 1 => array:2 [ "identificador" => "sec0060" "titulo" => "Data confidentiality" ] 2 => array:2 [ "identificador" => "sec0065" "titulo" => "Right to privacy and informed consent" ] ] ] 9 => array:2 [ "identificador" => "sec0070" "titulo" => "Authors’ contributions" ] 10 => array:2 [ "identificador" => "sec0075" "titulo" => "Conflict of interest" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-02-09" "fechaAceptado" => "2014-07-21" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec583249" "palabras" => array:4 [ 0 => "Chemoembolization" 1 => "Hepatocellular carcinoma" 2 => "Liver transplant" 3 => "Anatomic pathology" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec583248" "palabras" => array:4 [ 0 => "Quimioembolización" 1 => "Carcinoma hepatocelular" 2 => "Trasplante hepático" 3 => "Anatomía patológica" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveTo determine the degree of tumor necrosis in surgical specimens of hepatocellular carcinomas treated with microspheres preloaded with doxorubicin and to analyze the relationship between the degree of necrosis and (a) morphologic factors and (b) imaging biomarkers. Material and methodsWe studied the livers of 21 patients who had undergone selective arterial chemoembolization with DC beads (Biocompatibles, UK) before receiving liver transplants. ResultsImaging techniques detected 43 nodules (mean size, 25mm). Angiography showed 25 hypervascularized nodules, 12 slightly vascularized nodules, and 6 avascular nodules. A total of 81 hepatocellular carcinomas (mean size, 15mm) were detected in the specimens: two were capsular and two had vascular infiltration. The mean degree of necrosis after chemoembolization was 39%; necrosis was greater than 60% in 28 hepatocellular carcinomas and less than 60% in 52. The degree of necrosis correlated significantly with the time elapsed between the last chemoembolization treatment and liver transplantation (the degree of necrosis decreased as time increased), with the number of nodules in the specimen, and with capsular infiltration. When imaging techniques detected 1 or 2 nodules, there was a greater probability of achieving greater than 90% necrosis. No relation with the degree of necrosis achieved was found for the size of the nodules detected at imaging, the enhancement pattern, or the number of chemoembolization treatments. ConclusionThe degree of necrosis achieved depends on the time spent on the waiting list, on the number of nodules in the specimen, and on whether capsular infiltration is present." "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" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivoDeterminar el grado de necrosis tumoral en la pieza quirúrgica de hepatocarcinomas tratados con microesferas precargadas con doxorrubicina (QETA-DEB) y su relación con factores morfológicos y biomarcadores de imagen. Material y métodos21 pacientes a quienes se realizó quimioembolización arterial selectiva con partículas DC-Beads (Biocompatibles, UK) fueron posteriormente trasplantados y analizados los hígados histológicamente. ResultadosSe detectaron por diferentes técnicas de imagen 43 nódulos con un tamaño medio de 25mm. Angiográficamente eran 25 nódulos hipervascularizados, 12 discretamente vascularizados y 6 avasculares. En la pieza se encontraron 81 HCCs con un tamaño medio de 15mm.; dos presentaron infiltración vascular y otros dos infiltración capsular. La necrosis media conseguida tras QETA-DEB fue del 39% siendo >60% en 28 HCCs y <60% en 52. Encontramos correlación estadística entre el índice de necrosis conseguida con el tiempo que transcurre desde la última QETA-DEB hasta el trasplante (siendo significativamente menor la necrosis conforme aumenta el tiempo), con el número de nódulos encontrados en la pieza y con la infiltración capsular. Asimismo, podemos predecir que cuando por técnicas de imagen detectamos 1 ò 2 nódulos tendremos más probabilidad de conseguir de manera significativa índices de necrosis >90%. Sin embargo, ni el tamaño de los nódulos detectados por técnicas de imagen, ni el patrón de realce post-contraste ni el número de QETA-DEBs realizadas influye significativamente en la necrosis conseguida. ConclusiónLa necrosis producida depende del tiempo en lista de espera, del número de nódulos en la pieza y de la infiltración capsular del tumor." "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" => "Conclusión" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Zurera LJ, Espejo JJ, Lombardo S, Marchal T, Muñoz MC, Canis M, et al. Estudio histológico sobre el efecto de la quimioembolización con partículas precargadas con doxorrubicina en el hepatocarcinoma. Radiología. 2015;57:419–27." ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1350 "Ancho" => 1800 "Tamanyo" => 421189 ] ] "descripcion" => array:1 [ "en" => "(a) Axial hepatic CT image in artery phase; 50mm-hepatocarcinoma in segment 8 and areas of necrosis (a). (b) Hepatic angiography confirming hypervascularized tumor and another adjacent 9mm-hypovascular one (arrow) not found through CT. (c) After two (2) sessions of selective transarterial chemoembolizations with hydrogel microspheres preloaded with selective doxorubicine (DEB-TACE) the tumor response is complete. (d) Liver explanted 9 months after the last session of DEB-TACE. Only partial necrosis (30%) of the tumor (N) can be seen with peripheral areas of feasible tumor (♦). See microspheres (arrow) in the vicinity of tumor. (e) Microscopic image (H&E 10×) of a bigger tumor where areas of necrosis (N) and tumor (T) feasibility can be seen. (f) Microscopic image of the smaller hypovascular turmor (H&E 10×). Complete tumor (T) feasibility yet despite the presence of microspheres in the tumor bed (arrow head)." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1350 "Ancho" => 1800 "Tamanyo" => 319647 ] ] "descripcion" => array:1 [ "en" => "(a and b) Axial T1-weighted MRIs after the injection of gadolinium (artery phase). Three (3) 30, 20 and 20mm-hepatocarcinomas (arrows) can be seen. (c) Hepatic angiography (late phase) showing the tumors (arrows). (d) and (e) T1-weighted MRI axial images after the injection of gadolinium (artery phase). Partial response after one session of selective transarterial chemoembolizations with preloaded selective doxorubicin hydrogel beads (DEB-TACE) in the three (3) hepatocarcinomas (arrows) whose size has been reduced but have been enhanced peripherally. (f) Microscopic image (H&E 10×) of one of those tumors 10 months after DEB-TACE. Central necrosis (N) of 70% with a peripheral halo of tumor feasibility (♦)." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1374 "Ancho" => 1394 "Tamanyo" => 356402 ] ] "descripcion" => array:1 [ "en" => "(a) Hepatic angiography (late phase) 30mm-hypervascularized tumor in segment 6. (b) Coronal hepatic CT image in artery phase after three (3) sessions of selective transarterial chemoembolizations with preloaded doxorubicin hydrogel beads. The effect has been nonexistent persisting the complete tumor hypervascularization (arrow). (c) Microscopic image (H&E 10×) of tumor 13 months after the last session of chemoembolization. Complete tumor (T) feasibility with tumor infiltration of the capsule (C). (d) Microscopic image (cd 10× stain specifically staining the vascular wall in brown color). Tumor cells inside a vessel (arrows). In this liver another 10mm-hepatocarcinoma was found too." ] ] 3 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "tDEB-TACE→LT: time (in months) from the last session of transarterial chemoembolizations with preloaded selective doxorubicin hydrogel beads (DEB-TACE) elapsed up to liver transplantation (LT).HCV: Hepatitis C virus." "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">Number of patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21 \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">Age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">59 (41–65) \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">Etiology of cirrhosis</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Alcohol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 (38%) \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">HCV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 (48%) \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">HCV+alcohol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 (14%) \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">Hepatic function</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Child A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 (57%) \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">Child B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9 (43%) \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 " align="left" valign="top">Nodes in images \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">43 \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">1–2 nodes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14 patients \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">3–4 nodes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 patients \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">>4 nodes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 patients \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 " align="left" valign="top">Node sizes in images \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25mm (8–55mm) \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">≤20mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">22 nodes \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">21–30mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 nodes \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">31–40mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 nodes \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">>40mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 nodes \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">Angiographic patter of nodes</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hypervascular \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25 \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">Hypovascular \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 \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">Avascular \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" 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 " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">tDEB-TACE→LT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 months (0.5–10.5) \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">≤3 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 patients \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">4–6 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 patients \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">>6 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">11 patients \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab920084.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Demographic characteristics of patients." ] ] 4 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "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=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \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">Nodes in images \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">HCC in the piece</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top">Number of nodes found</td><td class="td" title="table-entry " align="left" valign="top">43 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">81</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="center" valign="top">rho=0.745 (p<0.001)</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top">Median size (mm)</td><td class="td" title="table-entry " align="left" valign="top">25±12 (8–55) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Image correlation (43)17mm(0–70mm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">New onset (38)9mm \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="center" valign="top">15mm (8–70mm)</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">Vascularization</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">HypervascularHypovascularAvascular \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25 (58.1%)12 (27.9%)6 (14.0%) \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><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">% Necrosis obtained</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">>90%60–90%<60% \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><td class="td" title="table-entry " colspan="2" align="center" valign="top">21 (25.9%)7 (8.6%)53 (65.4%)</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab920087.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Description of nodes studied through images (n=43) and in the surgical piece (n=81)." ] ] 5 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "DEB-TACE: transarterial chemoembolizations with preloaded selective doxorubicin hydrogel beads." "tablatextoimagen" => array:2 [ 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="" valign="top" scope="col" style="border-bottom: 2px solid black"> \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">>90% (n=21) \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">90–60% (n=7) \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"><60% (n=53) \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">Chi2p \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="5" align="left" valign="top">Angiographic pattern (n=43)</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hypervascular \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 (61%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (86%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 (44%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.387 \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">Avascular \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (17%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (17%) \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="5" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Capsular infiltration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 (100%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.024 \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">Vapsular infiltration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 (21%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.112 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top">Number of DEB-TACE</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">One \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="char" valign="top">7 (100%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37 (70%) \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 " align="left" valign="top">Two \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (19%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (9%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.158 \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">Three \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 (21%) \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 => "xTab920085.png" ] ] 1 => 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="" valign="top" scope="col" style="border-bottom: 2px solid black"> \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">Median \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">Median \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">Median \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">K–Wallis 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 " align="left" valign="top">Time DEB-TACE-LT (months) \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><td class="td" title="table-entry " align="char" valign="top">6 \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><td class="td" title="table-entry " align="char" valign="top"><0.001 \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">Number of nodes in image (n) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \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><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \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">Size pre-DEB-TACE (mm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">28.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22.71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22.67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.285 \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">Number of nodes in the piece (n) \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><td class="td" title="table-entry " align="char" valign="top">5 \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><td class="td" title="table-entry " align="char" valign="top"><0.001 \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">Size post-DEB-TACE (mm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15.76 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18.86 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13.96 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.029 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab920086.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Three (3) possible factors associated with the percentage of necrosis obtained in the nodes after DEB-TACE." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:28 [ 0 => array:3 [ "identificador" => "bib0145" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Liver transplantation for the treatment of small hepatocellular carcinoma in patients with cirrhosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V. 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Original article

Estudio histológico sobre el efecto de la quimioembolización con partículas precargadas con doxorrubicina en el hepatocarcinoma

L.J. Zureraa,

Corresponding author

lzurera61@gamil.com

Corresponding author.

, J.J. Espejoa, S. Lombardoa, T. Marchalb, M.C. Muñozc, M. Canisa, J.L. Monterod

a Unidad de Radiología Intervencionista, Hospital Universitario Reina Sofía, Córdoba, Spain

b Departamento de Anatomía Patológica, Hospital Universitario Reina Sofía, Córdoba, Spain

c IMIBIC, Hospital Universitario Reina Sofía, Córdoba, Spain

d Unidad de Hepatología, Hospital Universitario Reina Sofía, Córdoba, Spain

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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">&#40;a and b&#41; Axial T1-weighted MRIs after the injection of gadolinium &#40;artery phase&#41;&#46; Three &#40;3&#41; 30&#44; 20 and 20<span class="elsevierStyleHsp" style=""></span>mm-hepatocarcinomas &#40;arrows&#41; can be seen&#46; &#40;c&#41; Hepatic angiography &#40;late phase&#41; showing the tumors &#40;arrows&#41;&#46; &#40;d&#41; and &#40;e&#41; T1-weighted MRI axial images after the injection of gadolinium &#40;artery phase&#41;&#46; Partial response after one session of selective transarterial chemoembolizations with preloaded selective doxorubicin hydrogel beads &#40;DEB-TACE&#41; in the three &#40;3&#41; hepatocarcinomas &#40;arrows&#41; whose size has been reduced but have been enhanced peripherally&#46; &#40;f&#41; Microscopic image &#40;H&#38;E 10&#215;&#41; of one of those tumors 10 months after DEB-TACE&#46; Central necrosis &#40;N&#41; of 70&#37; with a peripheral halo of tumor feasibility &#40;&#9830;&#41;&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Transarterial chemoembolization &#40;TACE&#41; is a palliative treatment for patients with asymptomatic hepatocellular carcinoma &#40;HCC&#41;&#44; preserved liver function and lack of extrahepatic dissemination or vascular invasion &#40;intermediate stage-B&#8211;based on the criteria from the Barcelona Clinic Liver Diseases&#8211;BCLC&#41;&#46; Indications now include patients with early-stage HCC &#40;Barcelona Clinic Liver Diseases&#8211;A&#41; without surgical indication or local ablative therapies&#44; to patients waiting for liver transplantation &#40;LT&#41; &#40;in an effort to attain local control in the meantime&#41; or to downstage the tumor in patients who exceed the criteria for LT&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Not too long ago TACE started being used with preloaded doxorubicin hydrogel beads &#40;DEB-TACE&#41; that are better tolerated than conventional TACE &#40;cTACE&#41; with lipiodol<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>a chemotherapeutic agent<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>embolization particles &#40;gelfoam or polyvinyl alcohol&#41; since they release the drug in the liver blood stream more slowly and continually at the same time they reduce its passage into the systemic circulation &#40;yet despite the fact that they increases the dose&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">3&#44;4</span></a> Also it is more effective than conventional TACE in patients with recurrent and bilobar disease&#44; although it is not been confirmed to improve survival or reduce local relapse&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">5&#44;6</span></a> Nonetheless it does improve local response with respect to soft embolization&#8211;only embolization particles only&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The effect of TACE in HCC is necrosis that is evaluated through the imaging criteria of the European Association for the Study of the Liver&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">8&#8211;10</span></a> An acceptable anatomo-pathologic correlation has been observed<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">11&#8211;14</span></a> in studies performed on transplanted livers after cTACE&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">15&#8211;17</span></a> However&#44; the studies of anatomo-pathologic correlation of the antitumor effect of DEB-TACE<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">18</span></a> and the driving factors are scarce&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Our goal is to assess the degree of actual tumor necrosis caused by DEB-TACE and those factors it possibly correlates to based on the anatomo-pathologic examination of the livers explanted in the LT&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients</span><p id="par0025" class="elsevierStylePara elsevierViewall">From 2008 until April 2012&#44; we performed DEB-TACE in 120 cirrhotic patients with HCC of whom 21 were subsequently transplanted and then made up the sample of this retrospective study approved by the hospital ethics committee with the signing of the written informed consent to undergo the procedure&#46; Given that for the LT&#44; the Milan<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">1</span></a> criteria were followed&#44; for the DEB-TACE the following criteria were included&#58; &#40;1&#41; single tumor &#8804;5<span class="elsevierStyleHsp" style=""></span>cm that cannot be treated through local ablative therapies&#59; &#40;2&#41; up to three tumors none of them &#62;3<span class="elsevierStyleHsp" style=""></span>cm&#59; &#40;3&#41; lack of vascular invasion or extrahepatic dissemination through imaging methods&#59; &#40;4&#41; preserved liver function &#40;child A&#8211;B&#41;&#59; &#40;5&#41; acceptable coagulation condition &#40;prothrombin activity<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>55&#37;&#59; platelets<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>60&#44;000&#47;mm<span class="elsevierStyleSup">3</span>&#41;&#59; &#40;6&#41; adequate kidney function &#40;creatinine<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>1&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#41;&#59; and &#40;7&#41; patients exceeding the Milan criteria &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41; who were not initial candidates to undergo LT underwent DEB-TACE which led to tumor regression or downstaging were included in the waiting list&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The exclusion criteria were&#58; &#40;1&#41; portal thrombosis &#40;total or partial&#41;&#59; &#40;2&#41; significant hepatofugous portal flow in the angiography&#59; &#40;3&#41; contraindication of doxorubicin&#59; and &#40;4&#41; biliary obstruction&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The diagnosis of HCC was achieved through different image modalitiesand pieces of equipment &#40;because of our patients&#8217; heterogeneity&#41; and based on the criteria set by the clinical guidelines of the American Association for the Study of the Liver Diseases<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">8&#44;19</span></a> so the nodes were not biopsied yet six of them with atypical radiological behavior were tagged as HCC and then confirmed in an anatomo-pathological analysis&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Angiographic proceeding</span><p id="par0040" class="elsevierStylePara elsevierViewall">The right femoral artery was canalized&#44; after anesthetizing the area locally and with the patient under sedation &#40;1<span class="elsevierStyleHsp" style=""></span>cc of fentanyl and 2<span class="elsevierStyleHsp" style=""></span>cc of midazolam&#41; so that a standard introducer &#40;5F and 10<span class="elsevierStyleHsp" style=""></span>cm long&#41; could be introduced&#46; We selectively catheterized the celiac trunk and the superior mesenteric artery with multipurpose or cobra-type of catheters &#40;4&#8211;5F&#41; and after analyzing the arterial anatomic variables and verifying portal patency and its preferential hepatic flow&#44; the segmental branches of each tumor were supraselectively catheterized with microcatheters &#40;Progreat&#46; Terumo&#44; Leuven or Rapid Transit&#46; Cordis&#44; Miami&#44; USA&#41; to inject the hydrogel beads &#40;DC Bead&#46; Biocompatibles&#44; UK&#41; mixed with iodized contrast in a 1&#58;1 ratio&#46; These beads were preloaded with doxorubicin &#40;75<span class="elsevierStyleHsp" style=""></span>mg per vial&#41; 12<span class="elsevierStyleHsp" style=""></span>h before the procedure at the Pharmacy Service&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">We considered that the DEB-TACE was adequate when fluoroscopically we started seeing the reflux of the embolization material&#8211;even if we had not administered the entire particle load available&#46; This is why we always start the procedure with a 300&#8211;500<span class="elsevierStyleHsp" style=""></span>m&#956; vial followed by another of 500&#8211;700<span class="elsevierStyleHsp" style=""></span>m&#956; and when tumor devascularization was not adequate yet we completed it with 400&#8211;500<span class="elsevierStyleHsp" style=""></span>m&#956; beads &#40;Embozene&#44; Celonova Biosciences&#44; Newman&#44; USA&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">When the disease was bilobar&#44; the supraselective procedure was performed in a single session&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">No antibiotics or anti-inflammatories were administered in a prophylactic&#44; routine fashion and post-embolization syndrome&#8211;abdominal pain&#44; low-grade fever&#44; vomiting&#44; asthenia&#44; etc&#46; was managed individually and symptom-based&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Clinical-radiologic follow-up</span><p id="par0060" class="elsevierStylePara elsevierViewall">A strict clinical and analytical control was carried out &#40;hemogram and hepatorenal function test&#58; transaminase&#44; bilirubin&#44; alkaline phosphatase&#44; gamma-GT&#44; creatinine&#44; urea&#41; during the first week&#44; and then a first dynamic liver CT was performed 1 month after the DEB-TACE with a 64-crown multidetector CT&#44; VCT Light Speed&#44; &#40;GE Health Care&#44; Milwaukee&#44; Wi&#44; USA&#41;&#46; The images were interpreted by consensus among the radiologists involved in the study who measured the largest axis of the nodes detected and intra-tumor enhancement&#46; The nodes detected in the explanted liver but remained undetected though images before the LT were considered &#171;new onset&#187; nodes&#46; Applying the criteria from the European Association for the Study of the Liver&#44;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">8&#44;10</span></a> we did not perform a new DEB-TACE session when the response was complete but we did when it was partial&#46; When in presence of disease progression the patient was removed from the LT waiting list as the possibility of performing a new session or administering Sorafenib was individually evaluated for every patient&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">After this first control and given the retrospective character of our study the follow-up of patients on the waiting list was very variable and not constant &#40;with different image modalities and equipment since they came from different hospitals&#41; and in some of them we did not have any image modalities after the initial CT a month after the DEB-TACE yet no patient was lost during the follow-up&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Anatomopathologic study</span><p id="par0070" class="elsevierStylePara elsevierViewall">Once the LT was performed the anatomo-pathologist made 3&#8211;5<span class="elsevierStyleHsp" style=""></span>mm-thick coronal cuts and then transversal cuts of the explanted liver and the sections were fixed with 4&#37; formaldehyde &#40;buffered at pH 7 and stabilized in methanol&#41;&#46; One hepato-pathologist with more than 20 years of experience selected 2&#46;2&#8211;0&#46;3<span class="elsevierStyleHsp" style=""></span>cm sections and the nodes in order to process soak them in a paraffin solution&#44; cut them and dye them&#46; In her report&#44; she recorded macroscopic data of the explanted piece &#40;number and size of the nodes&#44; anatomo-pathologic type and capsular or vascular infiltration&#41;&#46; She also performed the microscopic study of each HCC subjectively assessing the percentage of necrosis in each one&#46; Based on former studies three groups were separated based on this percentage&#58; &#62;90&#37;&#44; 60&#8211;90&#37; and &#60;60&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">13&#44;16</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical analysis</span><p id="par0075" class="elsevierStylePara elsevierViewall">For the statistical analysis&#44; the IBM software&#44; PASW Statistics 18 &#40;version in Spanish language&#41; was used and the quantitative and qualitative variables were described&#46; We compared the quantitative variables &#40;pre- and post-DEB-TACE node size&#44; number of nodes pre- and post-DEB-TACE and time elapsed from the last chemoembolization until the LT was performed&#41; through the Kruskal&#8211;Wallis test and the Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test&#46; Qualitative variables &#40;angiographic pattern&#44; number of DEB-TACE and capsular&#47;vascular infiltration of the HCC&#41; with the Chi square test&#46; The existing correlation between the nodes detected in the image and those found in the piece was established with Spearman&#39;s correlation ratio&#46; Values were considered statistically significant when their level of reliability was beyond 95&#37; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><p id="par0080" class="elsevierStylePara elsevierViewall">Among the 21 patients studied&#44; 18 were male with a mean age of 56 years &#40;41&#8211;65 years&#41;&#46; The cause of the cirrhosis was alcoholic &#40;38&#37;&#41;&#44; hepatitis C virus &#40;48&#37;&#41; or both &#40;14&#37;&#41;&#46; Liver function was at a Child A &#40;57&#37;&#41; and Child B &#40;43&#37;&#41; stages&#46; A DEB-TACE session was performed in 16 patients&#44; two sessions in 3 patients and three sessions in two patients &#40;mean&#58; 1&#46;3 sessions&#47;patient&#41;&#46; The mean time elapsed from the last session to the LT was 6 months &#40;0&#46;5&#8211;10&#46;5 months&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">We detected &#40;with a minimum of 2 coincidental image modalities&#41; and treated 43 nodes with an average size of 25<span class="elsevierStyleHsp" style=""></span>mm &#40;8&#8211;55<span class="elsevierStyleHsp" style=""></span>mm&#41;&#46; Among them&#44; 25 were classified subjectively as hypervascularized through image modalities&#44; 12 were discreetly vascularized and 6 were avascular &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; In the piece 81 HCCs were found whose size was significantly reduced after the DEB-TACE &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#44; with a overall average size of 15<span class="elsevierStyleHsp" style=""></span>mm &#40;8&#8211;70<span class="elsevierStyleHsp" style=""></span>mm&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; 17<span class="elsevierStyleHsp" style=""></span>mm for the 43 detected through image modalities and 9<span class="elsevierStyleHsp" style=""></span>mm for the 38 new-onset HCCs&#46; Three &#40;3&#41; of the nodes disappeared&#44; two &#40;2&#41; presented with vascular infiltration and two others with capsular infiltration&#46; The median necrosis achieved after DEB-TACE was 39&#37;&#44; &#62;90&#37; in 21 HCCs&#44; 60&#8211;90&#37; in 7 and &#60;60&#37; in the remaining 53 &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">In 31 HCCs of 7 patients of the explanted piece&#44; necrosis was nonexistent&#46; Its mean size was 11<span class="elsevierStyleHsp" style=""></span>mm&#44; with an average 5 tumors&#47;patient and a median time elapsed from the last session to the LT of 7&#46;7 months&#46; Among the 28 HCCs of the 16 patients where necrosis was &#62;60&#37;&#44; the average size of the tumors was 20&#46;5<span class="elsevierStyleHsp" style=""></span>mm with an average 3&#46;6 tumors&#47;patient and a median time elapsed from the last session to the LT of 5&#46;7 months&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The statistical correlation between the index of necrosis and the time elapsed from the last DEB-TACE until the LT was high &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and it became significantly smaller with the passing of time&#46; This factor was related with the number of nodes found in the piece that also drove the necrosis in such a way that more tumors the smaller the necrosis &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; In 13 patients with &#8804;4 HCCs in the piece &#40;23 nodes&#44; 1&#46;7 tumors&#47;patient&#41; the mean necrosis was 78&#37;&#44; while in 8 patients with &#62;5 HCCs &#40;56 tumors&#44; 6&#46;6 tumors&#47;patient&#41; it was just 20&#37;&#46; When we detected one or two nodes through image modalities the odds of having indexes of necrosis beyond 90&#37; was greater &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Neither the size of the nodes before the DEB-TACE &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;285&#41; nor the number of procedures performed &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;158&#41; influenced necrosis significantly &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41; &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1 and 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">In the 25 hypervascularized nodes &#40;median size 25&#46;6<span class="elsevierStyleHsp" style=""></span>mm&#41; the median necrosis was 70&#37;&#44; in the 12 hypervascularized tumors &#40;median size 25&#46;9<span class="elsevierStyleHsp" style=""></span>mm&#41;&#44; it as 46&#37;&#44; and in the 6 avascular tumors &#40;median size 20&#46;3<span class="elsevierStyleHsp" style=""></span>mm&#41;&#44; it was 50&#37; but these differences were not statistically significant &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;387&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41; &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1 and 2</a>&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">There was capsular and vascular infiltration in one patient in some of the nodes&#44; in another patient just vascular infiltration and yet in another patient capsular infiltration only with an average 7&#46;3 HCCs&#47;patient&#46; In the first two patients the median necrosis was nonexistent and in the third one it was 33&#37;&#46; Although tumor vascular infiltration did not significantly influence necrosis &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;112&#41;&#44; the capsular infiltration did &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;024&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#44; yet these data are biased by the number of HCCs showing infiltration&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discussion</span><p id="par0115" class="elsevierStylePara elsevierViewall">In this study we have analyzed the effect of DEB-TACE on HCCs with hydrogel beads loaded with 75<span class="elsevierStyleHsp" style=""></span>mg of oral doxorubicin and saw that necrosis depends on the time elapsed until liver transplantation is performed&#44; on the number of nodes in the piece and on the tumor capsular infiltration&#46; The importance of these results is that there is one similar study published only<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">18</span></a> yet despite the fact that in many centers chemoembolization preloaded with particle has replaced both soft chemoembolization due to a better local response and conventional chemoembolization due to a better tolerance and response in advanced disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">3&#44;7</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">The local response &#40;degree of necrosis&#41; to chemoembolization in patients with HCC is usually analyzed based oto radiologic criteria &#40;mainly those of the European Association for the Study of the Liver&#41;&#46; With conventional TACE the radiopathologic correlation of tumoral necrosis has been variable&#44; with slightly more sensitivity of MR than CT&#44;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">11&#44;12</span></a> but it has not been studied much with DEB-TACE&#46; In our study&#44; we cannot correlate the local response of this modality with image modalities since they are not available on the days close to the transplant for many patients&#46; However we can analyze factors that can possibly condition the necrosis caused by the particles&#46; In our case one of the factors that influenced the necrosis the most was the time elapsed from the last treatment to the LT that is somehow related with the time on the waiting list&#46; The longer the time the smaller the index of necrosis&#46; As it has been described with the cTACE it was also related with the discordance between the number of tumors in the piece and those detected through image modalities and then treated supraselectively&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">12&#44;15&#44;20</span></a> Probably this is due to the fact that our patients on the LT waiting list are not followed up according to a protocol after their first liver CT &#40;in an attempt to detecting new-onset untreated tumors&#41; so in addition to a strict follow-up through image modalities we believe that repeated chemoembolization based on a protocol should be considered regardless the imaging response or in a lobar instead of a supra-selective fashion in order to operate on these new-onset tumors that are altering the desired antitumor effect&#46; Similarly and just as it happens with the cTACE<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">15&#44;21</span></a> the smaller the number of nodes detected through image modalities the greater the overall necrosis in the piece&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">The correlation between the degree of necrosis attained with the cTACE and tumor size has been dissimilar&#46; For some authors HCCs<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>2&#8211;3<span class="elsevierStyleHsp" style=""></span>cm have better complete indexes of response<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">12&#44;22</span></a> but other results say otherwise<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">23&#44;24</span></a> and some other authors even defend the benefit of this modality to downstage tumors &#60;5<span class="elsevierStyleHsp" style=""></span>cm<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">25</span></a>&#46; There is still little information about the DEB-TACE yet our results indicate that tumor size considered in isolation has little influence on necrosis somehow more driven by the other factors analyzed&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Hypervascularization has been&#44; in some cases&#44; a factor independent from tumor necrosis when treated with cTACE<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">12&#44;15&#44;26</span></a> but not in others&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">27</span></a> Although we have not found any statistically significant relation there is a clear trend in our cases&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Finally the tumor vascular and capsular infiltration is negatively correlated with the necrosis in HCC treated through cTACE and they are known factors of poor prognosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">12&#44;15</span></a> Our results with DEB-TACE confirm that there is little necrosis in cases with capsular infiltration since they are closely related with tumor multiplicity being this trend similar to vascular infiltration which by the way does not achieve statistical significance probably because of the few tumors presenting with capsular infiltration&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">This study has its limitations especially those derived from its retrospective character and the small number of patients&#46; Also the follow-up of the patients through image modalities has been irregular and inconsistent&#8211;non-protocolized due to the fact that our patients came from very different origins preventing the radio-pathologic correlation&#46; Unlike other authors&#44;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">28</span></a> it has not been a goal of this paper to analyze survival and all those factors determining it&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">In sum the time elapsed from the last DEB-TACE session to the LV&#44; the number and size of the tumors found in the piece and capsular infiltration are associated with the degree of necrosis&#44; but neither the tumor vascularization pattern&#44; the number of chemoembolization sessions or the size of tumors before the procedure had a strong influence&#46; When one or two HCCs are found through image modalities&#44; the odds of necrotizing are greater&#46; Also the DEB-TACE can downstage the size and stage of HCC significantly&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Ethical responsibilities</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Protection of people and animals</span><p id="par0150" class="elsevierStylePara elsevierViewall">The authors declare that no experiments with human beings or animals have been performed while conducting this investigation&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Data confidentiality</span><p id="par0155" class="elsevierStylePara elsevierViewall">The authors declare that in this article there are no data from patients&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Right to privacy and informed consent</span><p id="par0160" class="elsevierStylePara elsevierViewall">The authors declare that in this article there are no data from patients&#46;</p></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Authors&#8217; contributions</span><p id="par0165" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0170" class="elsevierStylePara elsevierViewall">Manager of the integrity of the study&#58; ZLJ&#44; CM&#44; MJL&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0175" class="elsevierStylePara elsevierViewall">Study Idea&#58; ZLJ&#44; E JJ&#44; CM&#44; MJL&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3&#46;</span><p id="par0180" class="elsevierStylePara elsevierViewall">Study Design&#58; ZLJ&#44; EJJ&#44; CM&#44; MJL&#44; MMC&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4&#46;</span><p id="par0185" class="elsevierStylePara elsevierViewall">Data Mining&#58; ZLJ&#44; EJJ&#44; LS&#44; CM&#44; MJL&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">5&#46;</span><p id="par0190" class="elsevierStylePara elsevierViewall">Data Analysis and Interpretation&#58; ZLJ&#44; EJJ&#44; LS&#44; MT&#44; MMC&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">6&#46;</span><p id="par0195" class="elsevierStylePara elsevierViewall">Statistical Analysis&#58; ZLJ&#44; MT&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">7&#46;</span><p id="par0200" class="elsevierStylePara elsevierViewall">Reference Search&#58; ZLJ&#44; EJJ&#44; LS&#44; MT&#44; CM&#44; MJL&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">8&#46;</span><p id="par0205" class="elsevierStylePara elsevierViewall">Writing&#58; ZLJ&#44; EJJ&#44; LS&#44; MMC&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">9&#46;</span><p id="par0210" class="elsevierStylePara elsevierViewall">Critical review of the manuscript with intellectually relevant remarks&#58; ZLJ&#44; EJJ&#44; LS&#44; MT&#44; CM&#44; MJL&#44; MMC&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">10&#46;</span><p id="par0215" class="elsevierStylePara elsevierViewall">Approval of final version&#58; ZLJ&#44; EJJ&#44; LS&#44; MT&#44; CM&#44; MJL&#44; MMC&#46;</p></li></ul></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conflict of interest</span><p id="par0220" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interests&#46;</p></span></span>"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To determine the degree of tumor necrosis in surgical specimens of hepatocellular carcinomas treated with microspheres preloaded with doxorubicin and to analyze the relationship between the degree of necrosis and &#40;a&#41; morphologic factors and &#40;b&#41; imaging biomarkers&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We studied the livers of 21 patients who had undergone selective arterial chemoembolization with DC beads &#40;Biocompatibles&#44; UK&#41; before receiving liver transplants&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Imaging techniques detected 43 nodules &#40;mean size&#44; 25<span class="elsevierStyleHsp" style=""></span>mm&#41;&#46; Angiography showed 25 hypervascularized nodules&#44; 12 slightly vascularized nodules&#44; and 6 avascular nodules&#46; A total of 81 hepatocellular carcinomas &#40;mean size&#44; 15<span class="elsevierStyleHsp" style=""></span>mm&#41; were detected in the specimens&#58; two were capsular and two had vascular infiltration&#46; The mean degree of necrosis after chemoembolization was 39&#37;&#59; necrosis was greater than 60&#37; in 28 hepatocellular carcinomas and less than 60&#37; in 52&#46; The degree of necrosis correlated significantly with the time elapsed between the last chemoembolization treatment and liver transplantation &#40;the degree of necrosis decreased as time increased&#41;&#44; with the number of nodules in the specimen&#44; and with capsular infiltration&#46; When imaging techniques detected 1 or 2 nodules&#44; there was a greater probability of achieving greater than 90&#37; necrosis&#46; No relation with the degree of necrosis achieved was found for the size of the nodules detected at imaging&#44; the enhancement pattern&#44; or the number of chemoembolization treatments&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The degree of necrosis achieved depends on the time spent on the waiting list&#44; on the number of nodules in the specimen&#44; and on whether capsular infiltration is present&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Determinar el grado de necrosis tumoral en la pieza quir&#250;rgica de hepatocarcinomas tratados con microesferas precargadas con doxorrubicina &#40;QETA-DEB&#41; y su relaci&#243;n con factores morfol&#243;gicos y biomarcadores de imagen&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">21 pacientes a quienes se realiz&#243; quimioembolizaci&#243;n arterial selectiva con part&#237;culas DC-Beads &#40;Biocompatibles&#44; UK&#41; fueron posteriormente trasplantados y analizados los h&#237;gados histol&#243;gicamente&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se detectaron por diferentes t&#233;cnicas de imagen 43 n&#243;dulos con un tama&#241;o medio de 25<span class="elsevierStyleHsp" style=""></span>mm&#46; Angiogr&#225;ficamente eran 25 n&#243;dulos hipervascularizados&#44; 12 discretamente vascularizados y 6 avasculares&#46; En la pieza se encontraron 81 HCCs con un tama&#241;o medio de 15<span class="elsevierStyleHsp" style=""></span>mm&#46;&#59; dos presentaron infiltraci&#243;n vascular y otros dos infiltraci&#243;n capsular&#46; La necrosis media conseguida tras QETA-DEB fue del 39&#37; siendo &#62;60&#37; en 28 HCCs y &#60;60&#37; en 52&#46; Encontramos correlaci&#243;n estad&#237;stica entre el &#237;ndice de necrosis conseguida con el tiempo que transcurre desde la &#250;ltima QETA-DEB hasta el trasplante &#40;siendo significativamente menor la necrosis conforme aumenta el tiempo&#41;&#44; con el n&#250;mero de n&#243;dulos encontrados en la pieza y con la infiltraci&#243;n capsular&#46; Asimismo&#44; podemos predecir que cuando por t&#233;cnicas de imagen detectamos 1 &#242; 2 n&#243;dulos tendremos m&#225;s probabilidad de conseguir de manera significativa &#237;ndices de necrosis &#62;90&#37;&#46; Sin embargo&#44; ni el tama&#241;o de los n&#243;dulos detectados por t&#233;cnicas de imagen&#44; ni el patr&#243;n de realce post-contraste ni el n&#250;mero de QETA-DEBs realizadas influye significativamente en la necrosis conseguida&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La necrosis producida depende del tiempo en lista de espera&#44; del n&#250;mero de n&#243;dulos en la pieza y de la infiltraci&#243;n capsular del tumor&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Zurera LJ&#44; Espejo JJ&#44; Lombardo S&#44; Marchal T&#44; Mu&#241;oz MC&#44; Canis M&#44; et al&#46; Estudio histol&#243;gico sobre el efecto de la quimioembolizaci&#243;n con part&#237;culas precargadas con doxorrubicina en el hepatocarcinoma&#46; Radiolog&#237;a&#46; 2015&#59;57&#58;419&#8211;27&#46;</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">&#40;a&#41; Axial hepatic CT image in artery phase&#59; 50<span class="elsevierStyleHsp" style=""></span>mm-hepatocarcinoma in segment 8 and areas of necrosis &#40;a&#41;&#46; &#40;b&#41; Hepatic angiography confirming hypervascularized tumor and another adjacent 9<span class="elsevierStyleHsp" style=""></span>mm-hypovascular one &#40;arrow&#41; not found through CT&#46; &#40;c&#41; After two &#40;2&#41; sessions of selective transarterial chemoembolizations with hydrogel microspheres preloaded with selective doxorubicine &#40;DEB-TACE&#41; the tumor response is complete&#46; &#40;d&#41; Liver explanted 9 months after the last session of DEB-TACE&#46; Only partial necrosis &#40;30&#37;&#41; of the tumor &#40;N&#41; can be seen with peripheral areas of feasible tumor &#40;&#9830;&#41;&#46; See microspheres &#40;arrow&#41; in the vicinity of tumor&#46; &#40;e&#41; Microscopic image &#40;H&#38;E 10&#215;&#41; of a bigger tumor where areas of necrosis &#40;N&#41; and tumor &#40;T&#41; feasibility can be seen&#46; &#40;f&#41; Microscopic image of the smaller hypovascular turmor &#40;H&#38;E 10&#215;&#41;&#46; Complete tumor &#40;T&#41; feasibility yet despite the presence of microspheres in the tumor bed &#40;arrow head&#41;&#46;</p>"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">&#40;a and b&#41; Axial T1-weighted MRIs after the injection of gadolinium &#40;artery phase&#41;&#46; Three &#40;3&#41; 30&#44; 20 and 20<span class="elsevierStyleHsp" style=""></span>mm-hepatocarcinomas &#40;arrows&#41; can be seen&#46; &#40;c&#41; Hepatic angiography &#40;late phase&#41; showing the tumors &#40;arrows&#41;&#46; &#40;d&#41; and &#40;e&#41; T1-weighted MRI axial images after the injection of gadolinium &#40;artery phase&#41;&#46; Partial response after one session of selective transarterial chemoembolizations with preloaded selective doxorubicin hydrogel beads &#40;DEB-TACE&#41; in the three &#40;3&#41; hepatocarcinomas &#40;arrows&#41; whose size has been reduced but have been enhanced peripherally&#46; &#40;f&#41; Microscopic image &#40;H&#38;E 10&#215;&#41; of one of those tumors 10 months after DEB-TACE&#46; Central necrosis &#40;N&#41; of 70&#37; with a peripheral halo of tumor feasibility &#40;&#9830;&#41;&#46;</p>"
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        "identificador" => "fig0015"
        "etiqueta" => "Figure 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 1374
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            "Tamanyo" => 356402
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        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">&#40;a&#41; Hepatic angiography &#40;late phase&#41; 30<span class="elsevierStyleHsp" style=""></span>mm-hypervascularized tumor in segment 6&#46; &#40;b&#41; Coronal hepatic CT image in artery phase after three &#40;3&#41; sessions of selective transarterial chemoembolizations with preloaded doxorubicin hydrogel beads&#46; The effect has been nonexistent persisting the complete tumor hypervascularization &#40;arrow&#41;&#46; &#40;c&#41; Microscopic image &#40;H&#38;E 10&#215;&#41; of tumor 13 months after the last session of chemoembolization&#46; Complete tumor &#40;T&#41; feasibility with tumor infiltration of the capsule &#40;C&#41;&#46; &#40;d&#41; Microscopic image &#40;cd 10&#215; stain specifically staining the vascular wall in brown color&#41;&#46; Tumor cells inside a vessel &#40;arrows&#41;&#46; In this liver another 10<span class="elsevierStyleHsp" style=""></span>mm-hepatocarcinoma was found too&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">tDEB-TACE<span class="elsevierStyleHsp" style=""></span>&#8594;<span class="elsevierStyleHsp" style=""></span>LT&#58; time &#40;in months&#41; from the last session of transarterial chemoembolizations with preloaded selective doxorubicin hydrogel beads &#40;DEB-TACE&#41; elapsed up to liver transplantation &#40;LT&#41;&#46;</p><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">HCV&#58; Hepatitis C virus&#46;</p>"
          "tablatextoimagen" => array:1 [
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                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"><span class="elsevierStyleItalic">Number of patients</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21&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">Age &#40;years&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">59 &#40;41&#8211;65&#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  " 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="elsevierStyleItalic">Etiology of cirrhosis</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Alcohol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8 &#40;38&#37;&#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>HCV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10 &#40;48&#37;&#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>HCV<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>alcohol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3 &#40;14&#37;&#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  " 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="elsevierStyleItalic">Hepatic function</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Child A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12 &#40;57&#37;&#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>Child B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9 &#40;43&#37;&#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  " 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  " align="left" valign="top"><span class="elsevierStyleItalic">Nodes in images</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">43&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>1&#8211;2 nodes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14 patients&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>3&#8211;4 nodes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7 patients&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>&#62;4 nodes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0 patients&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  " align="left" valign="top"><span class="elsevierStyleItalic">Node sizes in images</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25<span class="elsevierStyleHsp" style=""></span>mm &#40;8&#8211;55<span class="elsevierStyleHsp" style=""></span>mm&#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>&#8804;20<span class="elsevierStyleHsp" style=""></span>mm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22 nodes&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>21&#8211;30<span class="elsevierStyleHsp" style=""></span>mm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10 nodes&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>31&#8211;40<span class="elsevierStyleHsp" style=""></span>mm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6 nodes&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>&#62;40<span class="elsevierStyleHsp" style=""></span>mm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5 nodes&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="elsevierStyleItalic">Angiographic patter of nodes</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hypervascular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25&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>Hypovascular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&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>Avascular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" 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  " 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  " align="left" valign="top"><span class="elsevierStyleItalic">tDEB-TACE</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#8594;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">LT</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6 months &#40;0&#46;5&#8211;10&#46;5&#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>&#8804;3 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5 patients&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>4&#8211;6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5 patients&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>&#62;6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11 patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => "xTab920084.png"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Demographic characteristics of patients&#46;</p>"
        ]
      ]
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        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "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=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&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">Nodes in images&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">HCC in the piece</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top"><span class="elsevierStyleBold">Number of nodes found</span></td><td class="td" title="table-entry  " align="left" valign="top">43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">81</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="center" valign="top">rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;745 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top"><span class="elsevierStyleBold">Median size &#40;mm&#41;</span></td><td class="td" title="table-entry  " align="left" valign="top">25<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12 &#40;8&#8211;55&#41;&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="elsevierStyleBold">Image correlation &#40;43&#41;</span>17<span class="elsevierStyleHsp" style=""></span>mm&#40;0&#8211;70<span class="elsevierStyleHsp" style=""></span>mm&#41;&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="elsevierStyleBold">New onset &#40;38&#41;</span>9<span class="elsevierStyleHsp" style=""></span>mm&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="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="center" valign="top">15<span class="elsevierStyleHsp" style=""></span>mm &#40;8&#8211;70<span class="elsevierStyleHsp" style=""></span>mm&#41;</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="elsevierStyleBold">Vascularization</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hypervascular<span class="elsevierStyleHsp" style=""></span>Hypovascular<span class="elsevierStyleHsp" style=""></span>Avascular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25 &#40;58&#46;1&#37;&#41;12 &#40;27&#46;9&#37;&#41;6 &#40;14&#46;0&#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><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">&#37; <span class="elsevierStyleBold">Necrosis obtained</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#62;90&#37;<span class="elsevierStyleHsp" style=""></span>60&#8211;90&#37;<span class="elsevierStyleHsp" style=""></span>&#60;60&#37;&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><td class="td" title="table-entry  " colspan="2" align="center" valign="top">21 &#40;25&#46;9&#37;&#41;7 &#40;8&#46;6&#37;&#41;53 &#40;65&#46;4&#37;&#41;</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Description of nodes studied through images &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>43&#41; and in the surgical piece &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>81&#41;&#46;</p>"
        ]
      ]
      5 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">DEB-TACE&#58; transarterial chemoembolizations with preloaded selective doxorubicin hydrogel beads&#46;</p>"
          "tablatextoimagen" => array:2 [
            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="" valign="top" scope="col" style="border-bottom: 2px solid black">&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">&#62;90&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&#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">90&#8211;60&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>7&#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">&#60;60&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>53&#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">Chi<span class="elsevierStyleSup">2</span><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="5" align="left" valign="top"><span class="elsevierStyleItalic">Angiographic pattern &#40;</span>n<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">43&#41;</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hypervascular&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;61&#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">6 &#40;86&#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">8 &#40;44&#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;387&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>Avascular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;17&#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 &#40;0&#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">3 &#40;17&#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="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Capsular infiltration</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#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 &#40;0&#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">12 &#40;100&#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;024&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">Vapsular infiltration</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;5&#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 &#40;0&#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;21&#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;112&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="5" 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="5" align="left" valign="top"><span class="elsevierStyleItalic">Number of DEB-TACE</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>One&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">7 &#40;100&#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">37 &#40;70&#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  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Two&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;19&#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 &#40;0&#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">5 &#40;9&#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;158&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>Three&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;5&#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 &#40;0&#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;21&#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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                  <table border="0" frame="\n
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&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">6&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><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&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">Number of nodes in image &#40;n&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&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><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&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">28&#46;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22&#46;71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22&#46;67&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;285&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">Number of nodes in the piece &#40;n&#41;&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><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&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">15&#46;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18&#46;86&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#46;96&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;029&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Three &#40;3&#41; possible factors associated with the percentage of necrosis obtained in the nodes after DEB-TACE&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
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                            1 => "K&#46; Malagari"
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            3 => array:3 [
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
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                          "etal" => true
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                            1 => "C&#46; la Parra"
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                  ]
                  "host" => array:1 [
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                      "doi" => "10.1016/j.rx.2010.07.010"
                      "Revista" => array:6 [
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                        "volumen" => "53"
                        "paginaInicial" => "246"
                        "paginaFinal" => "253"
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                            0 => "R&#46; Sacco"
                            1 => "I&#46; Bargellini"
                            2 => "M&#46; Bertini"
                            3 => "E&#46; Bozzi"
                            4 => "A&#46; Romano"
                            5 => "P&#46; Petruzzi"
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                      ]
                    ]
                  ]
                  "host" => array:1 [
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                        0 => array:2 [
                          "etal" => false
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                            0 => "R&#46; Dhanasekaran"
                            1 => "D&#46;A&#46; Kooby"
                            2 => "C&#46;A&#46; Staley"
                            3 => "J&#46;S&#46; Kauh"
                            4 => "V&#46; Khanna"
                            5 => "H&#46;S&#46; KIM"
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                      ]
                    ]
                  ]
                  "host" => array:1 [
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            6 => array:3 [
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "Prospective randomized comparison of chemoembolization with doxorubicin-eluting beads and bland embolization with beadblock for hepatocellular carcinoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46; Malagari"
                            1 => "M&#46; Pomoni"
                            2 => "A&#46; Kelekis"
                            3 => "A&#46; Pomoni"
                            4 => "S&#46; Dourakis"
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                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00270-009-9750-0"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cardiovasc Intervent Radiol"
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                        "volumen" => "33"
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                        "paginaFinal" => "551"
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            7 => array:3 [
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                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "Carcinoma hepatocelular&#59; diagn&#243;stico&#44; estadificaci&#243;n y estrategia terap&#233;utica"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "R&#46; Vilana"
                            1 => "A&#46; Forner"
                            2 => "A&#46; Garcia"
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                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.rx.2010.05.003"
                      "Revista" => array:6 [
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            8 => array:3 [
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              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "Imaging response in the primary index lesion and clinical outcomes following transarterial locoregional therapy for hepatocellular carcinoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Riaz"
                            1 => "F&#46;H&#46; Miller"
                            2 => "L&#46;M&#46; Kulik"
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                  ]
                  "host" => array:1 [
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Article information

ISSN: 21735107
Original language: English

DOI:10.1016/j.rxeng.2015.07.004

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Year/Month	Html	Pdf	Total

2024 October	1	0	1
2024 September	1	0	1
2024 June	1	0	1
2024 April	1	0	1
2024 January	3	0	3
2023 December	1	0	1
2023 September	1	0	1
2023 August	1	0	1
2023 April	1	0	1
2023 January	2	0	2
2018 May	7	0	7
2018 April	10	2	12
2018 March	9	0	9
2018 February	12	2	14
2018 January	6	2	8
2017 December	11	2	13
2017 November	17	2	19
2017 October	16	2	18
2017 September	15	11	26
2017 August	24	7	31
2017 July	19	9	28
2017 June	23	8	31
2017 May	25	5	30
2017 April	28	2	30
2017 March	25	12	37
2017 February	15	3	18
2017 January	17	0	17
2016 December	17	4	21
2016 November	7	8	15
2016 October	37	9	46
2016 September	17	3	20
2016 August	13	7	20
2016 July	25	1	26
2016 June	25	11	36
2016 May	23	8	31
2016 April	25	8	33
2016 March	18	7	25
2015 November	0	1	1

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