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Value of positive resection margins in patients with pT2 prostate cancer. Implications for adjuvant treatment
Valor de los márgenes quirúrgicos de resección positivos en los pacientes con cáncer de próstata pT2. Implicaciones en el tratamiento adyuvante
J.E. Rosas-Navaa,
Corresponding author
rosas_nava_jes@hotmail.com

Corresponding author.
, F. Herranz-Amob, E.V. Paños-Fagundob, E. Lledó-Garcíab, F. Verdú-Tartajob, C. Hernández-Fernándezb
a Servicio de Urología, Hospital General de México DF, Mexico
b Servicio de Urología, Hospital General Universitario Gregorio Marañón, Madrid, Spain
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without clinical or radiological manifestations of metastasis&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Positive surgical margins &#40;PSMs&#41; were found in the biopsies of about 30&#37; of the patients that underwent PR&#44; which is a bad prognosis factor&#44; and biochemical recurrence and specific mortality increased in 5 years in between 12&#37; and 18&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The Clinical Guidelines of the European Association of Urology &#40;EAU&#41;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> and the National Comprehensive Cancer Network &#40;NCCN&#41;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> recommend adjuvant radiotherapy in patients with PSMs&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The aim of this study is to analyze the impact on biochemical relapse-free survival &#40;BRFS&#41; of tumor involvement of resection surgical margins in patients with localized stage prostate cancer &#40;pT2&#41; in the prostatectomy specimen&#44; and what it entails in adjuvant treatment&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Materials and methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">Between 1996 and 2007&#44; we performed RP in 536 patients with localized PCa &#40;pT2&#41;&#44; pN0-Nx and follow-up for more than 3 months&#46; In December of 2009 the database was updated&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Patients were classified prior to surgery in accordance with the D&#8217;Amico biochemical recurrence risk groups&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> For the pathological stage&#44; we used the 2002 TNM classification of the UICC&#46; No patient received neo or adjuvant therapy&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Postoperative follow-up consisted of determining PSA at 3 months&#44; 6 months until the fifth year and annually thereafter&#46; We considered biochemical recurrence &#40;BR&#41; to be persistent or increased PSA after radical prostatectomy above 0&#46;4<span class="elsevierStyleHsp" style=""></span>ng&#47;ml and increasing in the following determination&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">We performed a descriptive analysis of the variables analyzed employing the usual statistics for quantitative variables &#40;mean&#44; standard deviation&#44; median&#44; etc&#46;&#41; and qualitative &#40;absolute frequencies&#44; etc&#46;&#41;&#46; We used Fisher&#39;s exact test and the chi square test to assess the association between categorical variables&#46; We used the Kaplan&#8211;Meier method to assess survival and the long-rank test to assess differences between the different groups with confidence intervals at 95&#37;&#46; We performed a univariate analysis and subsequently adjusted it by means of a Cox proportional hazards model &#40;Enter method&#41;&#46; Statistical significance was considered when <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46; All calculations were performed with the SPSS version 15&#46;0 statistical software in Spanish&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Results</span><p id="par0050" class="elsevierStylePara elsevierViewall">The 536 patients had mean age of 64 and PSA of 7&#46;5<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#44; the other clinical variables are listed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; After the prostatectomy&#44; 17&#46;7&#37; of the patients had a Gleason score &#40;GS&#41;<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>8 and 21&#46;7&#37; had PSM&#46; The other pathological variables obtained after PR are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; In 49&#37;&#44; there was concordance between the GS of the specimen and that of the prostatectomy&#44; 47&#46;2&#37; were understaged &#40;52&#46;9&#37; for the GS of 6 and 29&#46;1&#37; for the GS of 7&#41; and 8&#46;1&#37; of GS 7 was understaged&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Follow-up of the series was 63&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>35 &#40;8&#8211;168&#41; with a median of 57 months&#46; At follow-up&#44; 112 &#40;20&#46;9&#37;&#41; patients had BR&#46; In 9 &#40;8&#37;&#41; patients post-prostatectomy PSA was never below 0&#46;4<span class="elsevierStyleHsp" style=""></span>ng&#47;ml &#40;biochemical persistence &#8211; BP&#41; and in 103 &#40;92&#37;&#41; cases&#44; PSA increased after a varying period of time&#44; with PSA less than 0&#46;4<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#46; 15&#46;1&#37; of the patients were classified as low risk&#44; 19&#46;8&#37; were categorized as intermediate risk and 45&#46;1&#37; of the high risk group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; presented BR&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">At the end of the trial&#44; 523 &#40;97&#46;6&#37;&#41; patients were alive&#58; 414 &#40;77&#46;2&#37;&#41; without BR&#44; 109 &#40;20&#46;3&#37;&#41; with BR and 13 &#40;2&#46;4&#37;&#41; had died&#46; 3 &#40;0&#46;5&#37;&#41; patients died from prostate cancer and 10 &#40;1&#46;7&#37;&#41; patients from other causes&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">59&#46;8&#37; of patients with BR were treated with salvage radiotherapy&#44; 19&#46;7&#37; with hormone therapy and 20&#46;5&#37; did not receive any salvage treatment&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The overall median actuarial BRSF of the series was 123&#46;6 months &#40;95&#37; CI&#58; 116&#46;8&#44; 130&#46;4&#41;&#46; The BRSF at 5 and 10 years was estimated at 78&#46;1 and 62&#46;4&#37; respectively&#46; Overall survival at 5 and 10 years was estimated at 97&#46;7 and 94&#46;2&#37; respectively and cancer-specific survival at 5 and 10 years was estimated at 99&#46;3 and 97&#46;1&#37; respectively&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">37&#46;9&#37; of patients with pathological involvement of surgical resection margins presented BR versus 16&#37; who did not &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">In the univariate analysis&#44; we observed an association of BR with the following pathological variables&#58; Gleason score &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#44; pathologic condition of surgical margins &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41; and capsular invasion &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#46; The rest of the data of the univariate analysis is given in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 3</a>&#46; We introduced the following variables in the multivariate analysis&#58; Gleason score&#44; surgical margins and capsular invasion&#46; Only the surgical margin &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and Gleason score<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>8 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; acted as independent factors of biochemical relapse &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">Table 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">We stratified according to surgical margin status &#40;SM&#41; and the prostatectomy GS in 4 risk groups&#58; 1&#41; &#40;&#8722;&#41; SM and GS<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>7&#59; 2&#41; &#40;&#8722;&#41; SM and GS<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>8&#59; 3&#41; &#40;&#43;&#41; SM and GS<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>7&#59; 4&#41; &#40;&#43;&#41; SM and GS<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>8&#46; The recurrence rate in these groups was 11&#46;7&#37;&#44; 37&#46;5&#37;&#44; 31&#37; and 60&#46;7&#37; respectively &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">The probability of recurrence at 5 and 10 years depending on these risk groups is described in <a class="elsevierStyleCrossRef" href="#tbl0030">Table 5</a>&#46; Patients with &#40;&#43;&#41; SM and GS<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>7 had a probability of relapsing at 5 and 10 years of 35&#37; and 50&#37;&#44; compared with 74&#37; and 87&#37; in the group with &#40;&#43;&#41; SM and GS<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>8 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0095" class="elsevierStylePara elsevierViewall">Radical prostate surgery currently offers excellent control for localized disease&#44; however&#44; one-third of the surgical specimens have PSMs&#44; seminal vesicle invasion and&#47; or extracapsular extension&#44; which increases the risk of recurrence&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">10</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">In our trial&#44; 21&#46;7&#37; of patients had PSMs&#44; out of which only 37&#46;9&#37; presented BR&#44; which was significant&#44; since only 16&#37; of patients that did not have PSMs suffered BR&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">The presence of positive margins increases the risk of biochemical and local recurrence after RP&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Moreover&#44; Stephenson et al&#46; found that patients with PSMs&#44; GS 8&#8211;10 and PSA doubling the time less than 10 months&#44; entail a higher risk of developing metastasis&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;13</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">The recurrence of prostate cancer following potentially curative surgery continues to be a dilemma&#44; because patients feel that they have lost their first chance to be cured and express the urgency to initiate another treatment in order to be cured&#46; However&#44; it is still difficult for physicians to decide on which treatment is more appropriate&#44; whether to initiate adjuvant therapy&#44; or to wait until PSA increases&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">In patients with PSMs or pT3&#44; radiation therapy immediately after RP increases biochemical progression-free survival&#44; local control and the risk of progression&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#8211;16</span></a> On the other hand&#44; it has recently been confirmed that there is a 10&#37; overall increase in survival in patients that receive adjuvant radiotherapy &#40;ART&#41;&#44; and an 8&#37; increase in metastasis-free survival&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Katz et al&#46; reported that patients with PSMs have the least probability of biochemical control with salvage radiation therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">ART is generally well tolerated and secondary toxic reactions are generally low grade&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#8211;21</span></a> It has been noted that the quality of life is greater in patients that receive ART&#44; as after 2 years&#44; patients who did not initially receive it&#44; begin with different salvage therapies that have more adverse effects&#44; and thus a greater impact on quality of life&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">ART is indicated in pT2 patients with PSMs&#44; however each case must be individualized according to its risk factors&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Leibovich et al&#46; observed that there was an 88&#37; BR-free rate in patients with pT2 and positive margins who were treated with ART compared to those that were only monitored&#44; in which the BR-free rate was 59&#37; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">A GS<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>8 in patients with organ-confined PCa &#40;pT2&#41; and PSMs significantly increases the likelihood of BR&#46; These patients would be those who would most benefit from ART&#44; while in 50&#37; of patients with PSMs and a GS<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>7&#44; ART could be considered as overtreatment&#59; moreover&#44; they can also be salvaged with radiation therapy in the event they suffer BR&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of interest</span><p id="par0135" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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          "clase" => "keyword"
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            0 => "Prostate cancer"
            1 => "Radical prostatectomy"
            2 => "pT2 stage"
            3 => "Prognostic factors"
            4 => "Recurrence"
            5 => "Positive surgical margins"
            6 => "Adjuvant radiotherapy"
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            0 => "C&#225;ncer de pr&#243;stata"
            1 => "Prostatectom&#237;a radical"
            2 => "Estadio pT2"
            3 => "Factores pron&#243;stico"
            4 => "Recidiva"
            5 => "M&#225;rgenes quir&#250;rgicos positivos"
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        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To analyze the impact on the recurrence-free biochemical survival of tumor involvement of surgical resection margins in patients with localized prostate cancer &#40;pT2&#41; in the prostatectomy specimen and its implications for adjuvant treatment&#46;</p> <span class="elsevierStyleSectionTitle">Materials and method</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Retrospective study of 536 patients with stage pT2 prostate cancer&#44; treated with radical prostatectomy between 1996 and 2007&#46; Subsequent to the prostatectomy&#44; the following variables were collected&#58; Gleason score&#44; pathological stage&#44; capsular invasion&#44; surgical margins and perineural invasion&#46; We performed a univariate analysis and subsequently adjusted it by means of a Cox proportional hazard model &#40;enter method&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">21&#46;7&#37; presented positive surgical margins and 20&#46;9&#37; developed biochemical recurrence after a mean follow-up of 57 months&#46; 37&#46;9&#37; of the patients with pathological involvement of the resection surgical margins presented biochemical recurrence against 16&#37; that did not have it &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; In the multivariate analysis&#44; only the surgical margin &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and the Gleason score greater or equal to 8 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; behaved as independent biochemical recurrence factors&#46; On stratifying the series according to these two variables&#44; we found that the patients with positive surgical margins and a Gleason score of &#8804;7 have a recurrence probability at 5 and 10 years of 35&#37; and 50&#37; against 74&#37; and 87&#37; in the group with positive surgical margins and a Gleason score of &#8805;8 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Patients with pT2 prostate cancer&#44; positive surgical margins and a Gleason score of &#8805;8 will benefit from adjuvant radiotherapy&#46; 50&#37; of the patients with positive margins and a Gleason score of &#8804;7 will not recur&#44; which means that the indication of adjuvant radiotherapy continues to be controversial&#46;</p>"
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        "resumen" => "<span class="elsevierStyleSectionTitle">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Analizar el impacto sobre la supervivencia libre de recidiva bioqu&#237;mica de la afectaci&#243;n tumoral de los m&#225;rgenes quir&#250;rgicos de resecci&#243;n en los pacientes con c&#225;ncer de pr&#243;stata en estadio localizado &#40;pT2&#41; en la pieza de prostatectom&#237;a y su implicaci&#243;n en el tratamiento adyuvante&#46;</p> <span class="elsevierStyleSectionTitle">Material y m&#233;todo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio retrospectivo de 536 pacientes con c&#225;ncer de pr&#243;stata en un estadio pT2 tratados con prostatectom&#237;a radical entre 1996 y 2007&#46; Posteriormente a la prostatectom&#237;a se recogieron las siguientes variables&#58; <span class="elsevierStyleItalic">score</span> de Gleason&#44; estadio patol&#243;gico&#44; invasi&#243;n capsular&#44; m&#225;rgenes quir&#250;rgicos e invasi&#243;n perineural&#46; Se realiz&#243; un an&#225;lisis univariante y posteriormente se ajust&#243; mediante un modelo de riesgos proporcionales de Cox &#40;m&#233;todo <span class="elsevierStyleItalic">enter</span>&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El 21&#44;7&#37; present&#243; m&#225;rgenes quir&#250;rgicos positivos y el 20&#44;9&#37; desarroll&#243; recidiva bioqu&#237;mica con una mediana de seguimiento de 57 meses&#46; El 37&#44;9&#37; de los pacientes con afectaci&#243;n patol&#243;gica de los m&#225;rgenes quir&#250;rgicos de resecci&#243;n present&#243; recidiva bioqu&#237;mica&#44; frente al 16&#37; de los que no la ten&#237;an &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; En el an&#225;lisis multivariante solo el margen quir&#250;rgico &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; y el <span class="elsevierStyleItalic">score</span> de Gleason mayor o igual a 8 &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; se comportaron como factores independientes de recidiva bioqu&#237;mica&#46; Al estratificar la serie seg&#250;n estas dos variables encontramos que los pacientes con m&#225;rgenes quir&#250;rgicos positivos y <span class="elsevierStyleItalic">score</span> de Gleason &#8804; 7 tienen una probabilidad de recidiva a los 5 y 10 a&#241;os del 35 y del 50&#37;&#44; frente al 74 y 87&#37; en el grupo con m&#225;rgenes quir&#250;rgicos positivos y <span class="elsevierStyleItalic">score</span> de Gleason &#8805; 8 &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;002&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Los pacientes con c&#225;ncer de pr&#243;stata pT2&#44; m&#225;rgenes quir&#250;rgicos positivos y <span class="elsevierStyleItalic">score</span> de Gleason &#8805; 8 se beneficiar&#225;n de una radioterapia adyuvante&#46; El 50&#37; de los pacientes con m&#225;rgenes positivos y un <span class="elsevierStyleItalic">score</span> de Gleason &#8804; 7 no presentar&#225;n recidiva&#44; por lo que la indicaci&#243;n de radioterapia adyuvante sigue siendo controvertida&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara">Please cite this article as&#58; Rosas-Nava JE&#44; et al&#46; Valor de los m&#225;rgenes quir&#250;rgicos de resecci&#243;n positivos en los pacientes con c&#225;ncer de pr&#243;stata pT2&#46; Implicaciones en el tratamiento adyuvante&#46; Actas Urol Esp&#46; 2011&#59;35&#58;272&#8211;76&#46;</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Actuarial biochemical relapse-free survival according to the surgical margin and Gleason score variables of the prostatectomy&#46;</p>"
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          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Statistics&#58; mean&#44; standard deviation and percentage&#46;</p>"
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                  \t\t\t\t"><span class="elsevierStyleItalic">Patients</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">42&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => """
                  <table border="0" frame="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Variable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Biochemical relapse&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Surgical margins</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Negative&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Perineural invasion</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Pathological stage</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>pT2a-b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>pT2c&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&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
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Variable&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8804;6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reference&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>7&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;13&nbsp;\t\t\t\t\t\t\n
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                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46; Jemal"
                            1 => "R&#46; Siegel"
                            2 => "J&#46; Xu"
                            3 => "E&#46; Ward"
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                    ]
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20610543"
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                    ]
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
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                            0 => "I&#46; Thompson"
                            1 => "C&#46; Tangen"
                            2 => "J&#46; Paradelo"
                            3 => "L&#46; Scott"
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                      ]
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                    0 => array:2 [
                      "doi" => "10.1001/jama.296.19.2329"
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                        0 => array:2 [
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                            1 => "M&#46; Han"
                            2 => "S&#46; Freedland"
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                      "titulo" => "Biochemical &#40;prostate specific antigen&#41; recurrence probability following radical prostatectomy for clinically localized prostate cancer"
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                          "etal" => false
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                            3 => "S&#46; Piantadosi"
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