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Original article
Usefulness of new schemes to group Fuhrman grades in clinical practice for clear cell renal tumor
Utilidad de los nuevos esquemas de agrupación de los grados de Fuhrman en la práctica clínica para el tumor renal de células claras
E. Morána,
Corresponding author
edumoran@comv.es

Corresponding author.
, R. Rogela, A. Sotoa, J.L. Ruiz-Cerdáa, A. Budíaa, J.V. Salomb, J.F. Jiménez-Cruza
a Servicio de Urología, Hospital Universitario y Politécnico La Fe, Valencia, Spain
b Servicio de Anatomía Patológica, Hospital Universitario y Politécnico La Fe, Valencia, Spain
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tumor size&#44; lymphovascular invasion&#44; presence of necrosis&#44; histologic subtype&#44; and degree of nuclear differentiation&#46;In 1982&#44; Fuhrman presented a histological classification with prognostic value in CCRC which years later has become essential for the management and prognosis of the renal tumor&#44; specifically for the CCRC&#44; where it has been validated&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The problem that arises from the use of Fuhrman grades &#40;GF&#41; is their complexity&#44; which leads to difficult reproducibility&#44; as shown in some studies where intraobserver and interobserver concordance is low&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Besides&#44; the fixing equipment&#44; the great heterogeneity of this type of tumors&#44; and the lack of standardization influence the minimum percentage of high-grade tumor necessary to classify it as such&#46; However&#44; in recent years&#44; there have been modifications to this classification to make it easier without losing its prognostic value&#46; These new classifications are Ficarra&#39;s&#44; who groups grades I and II into a single category&#44; keeping III and IV independent&#44; and Zisman&#39;s&#44; who groups grades I and II in a category and III and IV in another one&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#8211;5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In this context&#44; the objective of our work is to analyze whether the new FG categorization ratings in two and three groups&#44; proposals for CCRC&#44; are able to maintain the prognostic value against the traditional classification of 4 FG in a series of patients&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Population under study</span><p id="par0020" class="elsevierStylePara elsevierViewall">The sample consisted of 383 patients with CRCC treated with radical or partial nephrectomy between 1990 and 2009&#46; The following demographic data&#58; age&#44; sex&#44; presence of a single kidney&#44; form of presentation at diagnosis&#44; type of surgery&#44; and anatomopathological data&#58; number&#44; size&#44; unilateral or not&#44; location&#44; histological type&#44; tumor stage &#40;according to the 2009 TNM classification&#41;&#44; FG&#44; necrosis&#44; venous or lymphatic invasion&#44; and tumor stage were collected and analyzed&#46; The follow-up was performed by means of risk-based standardized scheme with computed tomography &#40;CT&#41; of the abdomen and pelvis&#44; chest X-ray&#47;CT&#44; abdominal ultrasound&#44; and blood test&#46; The evolution of these patients was analyzed according to the time of progression-free survival and the cancer-specific survival time&#46; The presence of local&#44; regional recurrence&#44; or distant metastasis was considered progression during the follow-up&#46; The cancer-specific survival time was estimated from the date of surgery until exitus for cancer-specific cause&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Nuclear grade categorization</span><p id="par0025" class="elsevierStylePara elsevierViewall">Initially&#44; the patients were classified according to Fuhrman&#39;s classical scheme in 4&#176; as shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">In grade I&#44; the cells have small nuclei &#40;10<span class="elsevierStyleHsp" style=""></span>&#956;m&#41;&#44; rounded&#44; even&#44; without nucleolus&#46; In grade II&#44; the cores are larger &#40;15<span class="elsevierStyleHsp" style=""></span>&#956;m&#41;&#44; of irregular morphology with nucleoli visible to high power fields &#40;&#215;400&#41;&#46; Grade III presents evident to medium magnifications &#40;&#215;100&#41;&#46; Grade IV presents multilobed nuclei with condensed chromatin clumps&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In order to carry out the study&#44; a uropathologist revised the samples&#44; and blindly&#44; at the first report&#44; reassigned the FG and the patients were reclassified into another two categories&#44; grouping grades I and II and keeping III and IV independent&#44; and another one grouping I and II in a grade and III and IV in another one&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Statistical analysis</span><p id="par0040" class="elsevierStylePara elsevierViewall">A descriptive analysis of the sample was carried out&#46; Subsequently&#44; we conducted a univariate analysis of progression-free survival and cancer-specific survival&#44; for which Kaplan&#8211;Meier survival curves were obtained both for the FG and for the different classifications proposed&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Then&#44; three multivariate analyses were conducted using Cox multiple regression&#44; with the time free of progression as a response variable and the cancer-specific survival time&#46; Age&#44; sex&#44; tumor size&#44; presence of necrosis and lymphovascular invasion&#44; pathologic stage&#44; and nuclear grade were considered explanatory variables&#46; In order to analyze the prognostic ability of the different ways of categorizing the FG&#44; the three analyses were carried out according to the classifications in 4&#44; 3&#44; or 2 categories&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Results</span><p id="par0050" class="elsevierStylePara elsevierViewall">The mean age of the 383 patients was 65&#46;5 years &#40;SD&#58; &#177;12&#46;9&#41;&#44; most of them being men &#40;64&#37;&#41;&#46; The most common presentation was the incidental finding &#40;58&#46;2&#37;&#41;&#44; the average size of these tumors at diagnosis being 6&#46;8<span class="elsevierStyleHsp" style=""></span>cm &#40;SD&#58; &#177;4&#46;2&#41;&#46; Of these&#44; 337 patients &#40;88&#37;&#41; were treated with radical nephrectomy&#44; and the rest &#40;46 patients&#41; with partial nephrectomy&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The anatomopathological and histological results are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; No statistical differences were found regarding the presence of sarcomatoid differentiation or microvascular involvement &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;08&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">During the follow-up&#44; there was local recurrence in 11&#46;7&#37; of the patients&#44; the median time to onset of these being 72 months &#40;CI 95&#37;&#58; 5&#8211;106&#41;&#46; The metastases appeared in 18&#46;8&#37;&#44; with a median time to them of 60 months &#40;CI 95&#37;&#58; 7&#8211;115&#41;&#46; The most frequent location of them was in the lung in 55&#46;8&#37;&#44; followed by the liver location &#40;14&#37;&#41;&#46; The median survival was 125 months &#40;CI 95&#37;&#58; 92&#8211;159&#41; after surgery&#44; the cancer-specific one being the most frequent cause of death in 66&#46;7&#37; of cases&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Kaplan&#8211;Meier curves were obtained for progression-free survival and cancer-specific survival &#40;<a class="elsevierStyleCrossRefs" href="#fig0010">Figs&#46; 2 and 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">In our analysis&#44; there were no differences between progression-free survival and cancer-specific survival between Fuhrman grades I and II &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;06 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;09&#44; respectively&#41; although there were differences between grades III and IV &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41;&#46; However&#44; differences were found between groups I<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>II vs III and IV &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#44; and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#44; and between I<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>II and III<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IV &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; in terms of progression-free survival and cancer-specific survival&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">In the multivariate analysis conducted&#44; the FG and classification variants showed independent predictive value &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001 in all three cases&#41; for both progression-free survival and for cancer-specific survival&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">In the first analysis&#44; the variable degree was coded into four categories &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#44; observing how the step from category I to II presents an increased relative risk &#40;1&#46;31&#41;&#44; although it is not statistically significant&#44; as they are the step from category II to III &#40;RR&#58; 2&#46;5&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; and from III to IV &#40;RR&#58; 2&#46;9&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; It was also classified into three categories &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41; finding that the step from category I<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>II to III involves an increased RR &#40;RR&#58; 2&#46;31&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#44; as well as the step from category III to IV &#40;RR&#58; 2&#46;47&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; As for the division into two categories&#44; the step from I<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>II to III<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IV presented a RR&#58; 2&#46;8 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Therefore&#44; the predictive capacity was maintained and similar using the three types of nuclear categorization&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0090" class="elsevierStylePara elsevierViewall">The renal tumor is the third most frequent urological malignancy after prostate cancer and bladder cancer&#46; The most common histological type&#44; in about 90&#37;&#44; is the CCRC&#46; From its study&#44; several prognostic factors have been considered&#44; among them the TNM stage&#44; clinical presentation&#44; lymphatic invasion&#44; degree of tumor necrosis&#44; size&#44; histologic subtype&#44; or nuclear grade&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The forecast in terms of survival and recurrence after treatment of CCRC is a key factor in planning the management of our patients&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">In 1932&#44; Hand and Broders described a correlation between the histological grade and the cancer-specific survival&#46; Until 1982&#44; multiple classifications were proposed&#44; but it was this year when Fuhrman et al&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> described the FG&#44; which to this day is the most frequently used nuclear grading and one of the most important prognostic factors&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">The FG has proven to be a prognostic factor independent of the tumor stage&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#8211;8</span></a> In the study by Rey et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> it was evaluated whether tumor necrosis&#44; microvascular invasion&#44; and invasion of the renal sinus could appear as independent prognostic factors&#46; It was evident that these new variables were associated with cancer-specific survival&#44; although they were not independent prognostic factors&#46; We did find&#44; however&#44; that the grade variable categorized as low-grade &#40;I<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>II&#41; and high-grade &#40;III<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IV&#41; presented with prognostic value independent of the tumor stage&#46; Our results are consistent with those described by this group&#46; In our analysis&#44; we introduced age&#44; sex&#44; tumor size&#44; presence of necrosis and lymphovascular invasion&#44; pathologic stage and grade as explanatory variables&#46; Of all&#44; the software only selected as independent the tumor stage and the FG in any of its rankings&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The widespread use of this classification is due to its proven relation with other pathological variables &#40;such as tumor stage&#41;&#44; so it is included in the main prognostic models like the UCLA Integrated Staging System or the Karakiewicz nomogram&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Nevertheless&#44; this is a grading system that is not exempt from limitations&#46; Thus&#44; it is a subjective method&#44; as it depends heavily on the knowledge and skill of the pathologist&#46; An insufficient sample or a faulty preservation and fixing system may alter the result&#46; The points on which this classification is based are mainly the nuclear characteristics&#44; the presence or absence of nucleoli and their size&#46; We have to point out that sometimes this type of tumors may be quite heterogeneous&#44; with areas of necrosis&#44; areas of oncocytic differentiation&#44; or with sarcomatoid areas&#46; In fact&#44; up to 3&#37; of renal carcinomas could be framed within the unclassifiable group&#46; Thus&#44; in the literature there are papers in which intra-and interobserver variability is not inconsiderable&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The paper by Ficarra et al&#46; presents a sample size similar to ours &#40;388&#41; and an interesting design&#44; where a pathologist&#44; blindly to a first classification&#44; recodes the 388 samples and evaluates the degree of concordance&#46; As a main conclusion&#44; a degree of consistency in the classification of <span class="elsevierStyleItalic">&#954;</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;44 was evidenced&#44; the differences being statistically significant&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">It is not the only paper in which the reproducibility of the Fuhrman classification has been criticized&#46; In the paper by Bektas et al&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> the intra- and interobserver variability of the Fuhrman nuclear grade is compared with regard to the two and three-grade systems&#46; This study included 110 patients with CCRC and analyzed the results of 5 anatomopathologists&#46; We found the best results for the classification into two grades vs that of 4 &#40;kappa index for the intra&#47;interobserver assessment of the classification into four grades&#58; 0&#46;48&#47;0&#46;41 and for the two-grade classification of 0&#46;67&#47;0&#46;62&#41;&#46; Consistent with the results of this study&#44; in a systematic review by Novara et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> it is concluded that the reproducibility of the classification of the FG in 4 grades must be improved&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">So&#44; there seems to be a need for review of this classification to fit it better into clinical practice&#46; The hypothesis of our paper was to demonstrate that the new classifications could keep the prognostic value&#46; With a similar objective&#44; there are two important papers&#44; one American and one European&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">In 2007&#44; Rioux-Leclercq et al&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> validated the classifications in two and three grades in a European multicenter study on 5453 patients&#46; This study showed that&#44; in a statistically significant way &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; the three classifications increased by 0&#46;6&#37; the ability to predict cancer-specific mortality&#44; metastasis&#44; or recurrence compared to models that did not include the Fuhrman classification or its variants&#46; In addition&#44; the new classifications increased prognostic accuracy in terms of survival&#44; recurrence&#44; and metastasis compared to the classical grades &#40;0&#46;5 vs 0&#46;6&#41;&#44; although not in a statistically significant way&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">An important point of this work is the selection of patients&#44; as not only patients with clear cell renal carcinoma were included&#44; but also those papillary and chromophobe&#46; It has been shown that the histologic type can be a confounding variable given the prognostic difference between the different histological subtypes&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> With this premise&#44; our paper only included patients with CCRC&#44; which is where it has been shown that the FG is really useful&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;13</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">This is an important difference from the American study by Sun et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> where only patients with CCRC were included&#46; This study also concluded that the use of the classification into two or three groups maintains the prognostic value&#46; However&#44; the heterogeneity of the evolution of the patients with grade III and IV is clarified&#46; In this regard&#44; in our study&#44; we did show a different risk in the chance of local&#44; regional recurrence of metastasis and cancer-specific survival between these two groups&#46; This difference in evolution may be because patients with Fuhrman grade IV often have other factors that cloud the outlook such as greater tumor size&#44; higher degree of necrosis&#44; or increased microvascular involvement and sarcomatoid differentiation&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;11</span></a> Therefore&#44; they would present a different evolution to grade 3 and they should be classified separately&#46; However&#44; in our series of patients we found no differences in these factors between grades III and IV&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Our results confirm the hypothesis that the simplified classifications of the FG are equally valid and accurate to the classic one for CCRC prognosis&#46; These classifications are intended to identify the patients with tumor progression and group them into risk groups&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Thus&#44; we believe that dividing the patients into low &#40;I<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>II&#41;&#44; intermediate &#40;III&#41;&#44; and high grade &#40;IV&#41; does not imply a loss of information with respect to the traditional classification&#46; After 50 months of follow-up&#44; grades III and IV have a different evolution in terms of progression-free survival&#44; so in our health area we would recommend the use of the classification into three categories&#44; which is closer to the reality of the patients&#46; We will consider that in the current era of antiangiogenic targeted therapies&#44; a correct forecast-based classification is essential to provide the best adjuvant treatment if necessary&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">However&#44; at present&#44; there is no consensus on which of the two ratings best represents the reality of the CCRC&#44; so more studies are needed to establish the basis of these new classifications&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Our study has the obvious limitations of a retrospective study and a small sample size compared with other series&#44; although the findings acquired are similar to those of other groups&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conclusions</span><p id="par0160" class="elsevierStylePara elsevierViewall">The amendments to the classification of Fuhrman nuclear grade into three or two grades maintain the validity and accuracy as independent prognostic factor for recurrence-free survival&#44; metastasis&#44; and cancer-specific survival&#46; The classification into three grades represents the outcome of the patients with CCRC better&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of interest</span><p id="par0165" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To evaluate if re-grading renal cell carcinoma &#40;CRCC&#41; in two or three-tiered grading schemes vs the traditional Fuhrman classification maintains the same prognostic value&#46;</p> <span class="elsevierStyleSectionTitle">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A study of a cohort of 383 treated CRCC with radical or partial nephrectomy between 1990 and 2009 was made&#46; We analyzed the demographic data&#44; evolution and survival of these patients&#46; An uropathologist reassigned the Fuhrman grades blindly to the first classification&#46; In order to study if the prognostic value was maintained with the different classification&#44; three Cox multivariate regression analysis were performed&#44; classifying the variable of grade into four categories&#58; &#40;I-II-III-IV&#41;&#44; into three &#40;I<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>II-III-IV&#41; and into two &#40;I<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>II-III<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IV&#41;&#46; The explanatory variables were&#58; age&#44; gender&#44; tumor size&#44; study stage and grade&#46; The response variables were progression-free survival &#40;local-regional recurrence&#47;metastasis&#41; and cancer specific survival time&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The median overall survival was 125 months &#40;95&#37; CI&#58; 92&#8211;159&#41;&#46; In the three multivariate analyses carried out&#44; the Fuhrman classification showed independent predictive value &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41; compared to progression-free survival and cancer specific survival&#46; The predictive power was maintained in the new classifications&#46; In the three categories&#44; the changing from grade I<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>II to III meant RR&#58; 2&#46;31 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41; and from grade III to IV RR&#58; 2&#46;47 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41; and in two-tiered classification an RR&#58; 2&#46;8 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; was found when changing from I<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>II to III<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IV&#46;</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Our results show that categorizing the Fuhrman grade into three or two-tiered grading schemes provide the same predictive accuracy on progressive free survival and cancer specific survival&#46; Grades III and IV have different outcomes so that the three-tiered classification seems to be more appropriate to described the course of these patients&#46;</p>"
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      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Evaluar si la re-clasificaci&#243;n de los carcinomas renales de c&#233;lulas claras &#40;CRCC&#41; en dos o tres grados de Fuhrman &#40;GF&#41; frente a la clasificaci&#243;n cl&#225;sica mantiene su valor pron&#243;stico&#46;</p> <span class="elsevierStyleSectionTitle">Material y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio sobre una cohorte de 383 CRCC tratados con nefrectom&#237;a radical&#47;parcial &#40;1990-2009&#41;&#46; Se analizaron datos demogr&#225;ficos&#44; evoluci&#243;n y supervivencia de los pacientes&#46; Un uropat&#243;logo reasign&#243; los grados de Fuhrman de forma ciega al informe original&#46; Para estudiar si se manten&#237;a el valor pron&#243;stico con las distintas clasificaciones se realizaron tres an&#225;lisis de regresi&#243;n m&#250;ltiple de Cox&#44; categorizando la variable grado en 4 categor&#237;as&#40;I-II-III-IV&#41;&#44; en tres &#40;I<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>II-III-IV&#41; y en dos &#40;I<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>II-III<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IV&#41;&#46; Las variables explicativas fueron&#58; edad&#44; sexo&#44; tama&#241;o tumoral&#44; estadio y grado&#46; Las variables respuesta fueron&#58; tiempo de supervivencia libre de progresi&#243;n &#40;recidiva locorregional&#47;met&#225;stasis&#41; y de supervivencia c&#225;ncer-espec&#237;fica&#46;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La mediana de supervivencia global fue de 125 meses &#40;IC 95&#37;&#58; 92-159&#41;&#46; En los tres an&#225;lisis multivariantes el grado de Fuhrman demostr&#243; valor predictivo independiente &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0001&#41; frente al estadio para la supervivencia libre de progresi&#243;n y supervivencia c&#225;ncer-espec&#237;fica&#46; El valor pron&#243;stico se mantuvo en las nuevas clasificaciones&#46; En la de tres categor&#237;as el paso del grado I<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>II al III present&#243; un RR&#58; 2&#44;31&#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0001&#41; y del grado III al IV un RR&#58; 2&#44;47&#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0001&#41; y en la de dos categor&#237;as se observ&#243; un RR&#58; 2&#44;8 &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; al pasar del grado I<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>II al III<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IV&#46;</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La categorizaci&#243;n en dos o tres grupos del grado de Fuhrman mantiene la capacidad predictiva sobre la supervivencia libre de progresi&#243;n y c&#225;ncer-espec&#237;fica&#46; Los grados III y IV presentan evoluciones distintas&#44; por lo que la clasificaci&#243;n en tres categor&#237;as parece m&#225;s adecuada para describir la evoluci&#243;n de estos pacientes&#46;</p>"
      ]
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara">Please cite this article as&#58; Mor&#225;n E&#44; et al&#46; Utilidad de los nuevos esquemas de agrupaci&#243;n de los grados de Fuhrman en la pr&#225;ctica cl&#237;nica para el tumor renal de c&#233;lulas claras&#46; Actas Urol Esp&#46; 2012&#59;36&#58;352&#8211;8&#46;</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">From left to right and from top to bottom Fuhrman grades I&#44; II&#44; III&#44; and IV&#46;</p>"
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                  \t\t\t\t" style="border-bottom: 2px solid black">Stage &#40;according to 2009 TNM&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">IV&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">21 &#40;5&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">72 &#40;18&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">248 &#40;64&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">176 &#40;46&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">95 &#40;24&#46;8&#37;&#41;&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">II&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">135 &#40;35&#46;2&#37;&#41;&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">III&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">95 &#40;24&#46;8&#37;&#41;&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
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                  \t\t\t\t">III&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">40 &#40;10&#46;4&#37;&#41;&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
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                  \t\t\t\t">&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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