renal cell carcinoma ( rcc ) is representative kidney cancer and has increased annually in the recent 2 decades .
although surgery remains the standard curative treatment for rcc , approximately 30% of patients with rcc develop metastatic disease after surgery , and approximately one third of patients with rcc have metastasis at the time of diagnosis .
several prognostic parameters have been evaluated and grade , histologic subtype , and stage remain important prognostic parameters in localized rcc . in addition , some preoperative parameters , including platelet count , c - reactive protein ( crp ) , and erythrocyte sedimentation rate have been considered for their prognostic relevance .
thrombocytosis ( tc ) , particularly secondary type has been regarded as a poor prognostic factor in many malignant diseases including gastric , gynecologic , and lung cancer .
recent studies have demonstrated an association of lower survival after operation with reactive tc for variable type of cancer , platelet count could have relation with the systemic inflammatory response , even though the exact relation between inflammation , platelet , and cancer outcomes is still not known .
the purpose of this study is to examine the association of preoperative tc with the prognosis of nonmetastatic rcc patients .
this study was approved by the ethics committee of yeungnam university school of medicine and informed consents were waived because the operations were done between 1997 and 2009 . in this
study the medical records of 187 patients who underwent radical nephrectomy for nonmetastatic rcc between july 1997 and june 2009 were reviewed retrospectively .
all patients were examined by routine hematologic laboratories and radiologic imaging including chest x - ray and abdominal computed tomography .
the definition of tc was platelet count400,000 l , and patients were divided into 2 groups by presence of preoperative tc .
tumor stage was reassigned using the 2002 tnm classification of the american joint committee on cancer ( ajcc ) .
postoperatively , every 3 or 6 month , all patients were evaluated for the first 2 years and every 6 months for next 2 years , and annually thereafter .
preoperative variabels including sex , gender , platelet count , neutrophil to lymphocytes ratio ( nlr ) , platelet to lymphocyte ratio ( plr ) , tumor size , tumor grade , histology and t stage were recorded .
moreover , distant metastasis during follow - up periods was also represented as a variable .
fisher exact test and chi - square test were used for comparison of discrete variables between the 2 groups .
receiver operating characteristics ( roc ) curves were generated to determine cutoff points for nlr and plr .
the overall survival ( os ) and cancer - specific survival ( css ) were estimated using the kaplan - meier survival analysis and the log - rank test .
univariate and multivariable analysis was fulfilled using the cox proportional hazard model and logistic regression for assessment of significant parameters associated with survival .
in this study the medical records of 187 patients who underwent radical nephrectomy for nonmetastatic rcc between july 1997 and june 2009 were reviewed retrospectively .
all patients were examined by routine hematologic laboratories and radiologic imaging including chest x - ray and abdominal computed tomography .
the definition of tc was platelet count400,000 l , and patients were divided into 2 groups by presence of preoperative tc .
tumor stage was reassigned using the 2002 tnm classification of the american joint committee on cancer ( ajcc ) .
postoperatively , every 3 or 6 month , all patients were evaluated for the first 2 years and every 6 months for next 2 years , and annually thereafter .
preoperative variabels including sex , gender , platelet count , neutrophil to lymphocytes ratio ( nlr ) , platelet to lymphocyte ratio ( plr ) , tumor size , tumor grade , histology and t stage were recorded .
moreover , distant metastasis during follow - up periods was also represented as a variable .
fisher exact test and chi - square test were used for comparison of discrete variables between the 2 groups . receiver
operating characteristics ( roc ) curves were generated to determine cutoff points for nlr and plr .
the overall survival ( os ) and cancer - specific survival ( css ) were estimated using the kaplan - meier survival analysis and the log - rank test .
univariate and multivariable analysis was fulfilled using the cox proportional hazard model and logistic regression for assessment of significant parameters associated with survival .
the mean follow - up period was 59.342.1 months and patients ' mean age was 56.011.7 years . mean tumor size was 5.22.9 cm .
twenty patients ( 10.7% ) had t3 or t4 tumors , and 20 patients ( 10.7% ) had preoperative tc .
thirty patients ( 16.0% ) developed metastasis and 9 patients ( 4.8% ) died during follow - up period .
the cutoff value of nlr was 1.81 ( area under the curve [ auc]=0.547 ; sensitivity , 0.5 ; specificity , 0.51 ) and plr was 128.7 ( auc=0.703 ; sensitivity , 0.67 ; specificity , 0.51 ) in the roc curve ( table 1 ) .
preoperative tc showed significant correlation with t stage ( p=0.028 ) , and metastasis ( p=0.001 ) , nlr1.81 ( p=0.003 ) , plr128.7 ( p=0.001 ) , but not with age , tumor histology subtype , gender , grade or tumor size ( table 2 ) . in kaplan - meier analysis using univariate log - rank test , css rate ( p=0.013 ) and os rate ( p=0.012 ) showed significant association with preoperative tc ( fig .
1 ) . tc , t stage , tumor size , and distant metastasis were significantly influencing parameters for css in both univariate and multivariable analysis . controlling for pathological tnm stage , tumor size and fuhrman grade , cox proportional hazards model for css rates showed that preoperative tc was an independent prognostic factor ( p=0.025 ) ( table 3 ) .
cox proportional hazards model for os rates showed that distant metastasis was an independent prognostic factor in multivariable analysis ( p=0.001 ) ( table 4 ) .
the european association of urology guidelines advise use of the tnm classification , fuhrman nuclear grade , and histological subtype for treatment of rcc .
the pathological stage according to tnm classification is the most important prognostic factor in rcc , followed by fuhrman grade .
many recent studies have examined platelet counts and tc as a useful prognostic factor in predicting survival and recurrence of rcc .
tc has also been reported in various malignancies and has been investigated as a prognostic factor .
primary tc is due to clonal tc and occurs in chronic myelodysplastic or myeloproliferative disorders .
secondary tc has been studied in many malignancies , including liver , gastrointestinal tract , lung , cervix , and others .
several theories have been suggested on how tc may be related to worse survival and the metastatic potential in malignancy .
one theory , tc in rcc patients may increase tumorigenesis by increasing platelet - derived growth factor , which is a mitogen for various cell types . according to another theory
in addition , platelets may provide for the adherence , penetration , and sequestration of malignant cells through the endothelial wall .
many cytokines including interleukin-6 or interleukin-11 , stem cell factor , granulocyte - macrophage colony - stimulating factor , and thrombopoietin are assumed to contribute to tc .
tc has been investigated as a valuable prognostic factor in predicting survival and recurrence in rcc patients . in their retrospective study of 1,422 patients who underwent radical or partial nephrectomy for rcc , either localized or metastatic , wosnitzer et al .  
however , when excluding metastatic patients , tc was not an independent predictor of os and css .
a different result was reported by brookman - may et al .   in their study of 3,139 patients who underwent surgery for rcc at four centers ,
preoperative tc was an independent predictor for decreased css in localized rcc patients and tc had no independent influence on css in metastatic disease . in a review of the records of 204 patients with rcc who underwent radical nephrectomy , o'keefe et al
.   reported that the overall and cancer specific death rate in 26 patients with tc was 50% and 42% .
however , in the remaining the normal platelet counts 178 patients , the same variables were 15.2% and 7.3% . in their study the cancer - specific death rate was 5 times greater in patients with tc .
they concluded that tc was a potent independent prognostic factor in patients with localized rcc .
cho et al . , who studied the association of tc and preoperative crp elevation with prognosis of nonmetastatic rcc patients in korea , found that crp and tc were significant prognostic factors associated with recurrence - free survival in univariate analysis , whereas multivariate analysis showed that tc was not an independent prognostic factor but crp was . in the current study , significantly lower os and css was observed in the tc group and tc , t stage , tumor size , and distant metastasis were significantly influencing parameters for css in both univariate and multivariable analysis . controlling for other parameters ,
reported that preoperative tc is a significant prognostic factor in localized rcc patients and tc was more frequent in advanced stage rcc patients , and patients with preoperative tc had worse survival compared to patients with normal platelet counts .
nlr is recently , one of the most investigated inflammation prognostic markers of postoperative outcome .
in fact , as it has relation with inflammatory response , the role in identifying patients with high - risk has been suggested in noncancer and cancer patients .
different studies have emphasized the role of high for detection of poorer prognosis cancer patients , in terms of both overall and cancer disease - free survival and general comorbidities .
plr was identified as a prognostic marker in advanced gastric cancer patients treated with chemotherapy , however mainly the studies are retrospective and pertain to only a few kinds of cancer . in our study ,
( p=0.003 ) , plr1.28.7 ( p=0.001 ) , but nlr and plr were not significant influencing factors for css in both univariate and multivariable analysis .
limitations of this study include the retrospective data assessment and no information was available concerning performance status , symptoms at the time of diagnosis , and further hematologic laboratory parameters such as crp or hematocrit , and platelet count was assessed only before the operation .
furthermore , only the influence of tc on os and css was evaluated , but not on recurrence - free survival , which can also be of interest .
based on the results of the current study preoperative tc is a significant predictor for determining prognosis in nonmetastatic rcc patients and patients with preoperative tc had worse survival compared to patients with normal platelet counts .
thus , preoperative platelet count may be clinically useful for risk stratifying patients undergoing surgery for nonmetastatic rcc .
 purposethe aim of this study was to examine the association of preoperative thrombocytosis with the prognosis of patients with nonmetastatic renal cell carcinoma ( rcc).materials and methodswe conducted a retrospective analysis of 187 patients who underwent a radical nephrectomy for nonmetastatic rcc between july 1997 and june 2009 . 
 thrombocytosis was defined as a platelet count400,000 l , and patients were divided into 2 groups according to presence of preoperative thrombocytosis , and the cancer - specific survival rates and overall survival rates of the 2 groups after radical nephrectomy were compared.resultsthe mean age of the patients was 56.011.7 years and the mean follow - up period was 59.342.1 months ; there were 20 patients with preoperative thrombocytosis . 
 thirty patients developed metastases and 9 patients died during the follow - up period . in kaplan - meier analysis using a univariate log - rank test , 
 both cancer - specific survival rate ( p=0.013 ) and overall survival rate ( p=0.012 ) showed significant association with preoperative thrombocytosis . 
 controlling for pathological tnm stage , fuhrman grade and tumor diameter , the cox proportional hazards model for cancer - specific survival rates showed that preoperative thrombocytosis was an independent prognostic factor ( p=0.025).conclusionspreoperative thrombocytosis was associated with poorer prognosis in patients with nonmetastatic rcc . 
 thus , preoperative platelet count may be clinically useful for risk stratification of patients undergoing surgery for nonmetastatic rcc . 
INTRODUCTION
MATERIALS AND METHODS
1. Patients
2. Statistical analysis
RESULTS
DISCUSSION
CONCLUSIONS