The preoperative prognostic nutritional index is an independent predictor of survival in patients with renal cell carcinoma

ObjectiveAccurate postoperative stratification of patients with renal cell carcinoma (RCC) in distinct prognostic groups is essential for tailoring follow-up, medical therapy, and inclusion in clinical trials. Increasing evidence suggests that Onodera׳s prognostic nutritional index (PNI) is a stage- and grade-independent predictor of poor outcomes in patients with cancer, but there are no data in RCC.Materials and methodsWe reviewed medical records of 1,344 patients with RCC who underwent radical or partial nephrectomy at the Medical University of Vienna and the University of California—Los Angeles between 1991 and 2012. Associations with cancer-specific survival were assessed with univariable and multivariable Cox proportional hazards models. Discrimination was measured with the C-index.ResultsThe median postoperative follow-up was 40 months. An increase of PNI by 1 unit was associated with a decrease in the risk of death from RCC by 7% (hazard ratio = 0.93, P<0.001). In multivariable analyses, the PNI was an independent prognostic factor (P<0.001). Adding the PNI improved the discrimination of a base model by 0.4%.ConclusionsThe PNI is an independent prognostic factor in patients with RCC. Its use increases the accuracy of established prognostic factors. PNI may be a meaningful adjunct for tailoring surveillance, medical therapy, and clinical trial design.     

High perirenal fat thickness predicts a poor progression-free survival in patients with localized clear cell renal cell carcinoma

Objectives

The aim of the study was to assess the association between the progression-free survival (PFS) and perirenal fat thickness (PFT) in a population of histopathologically confirmed, localized clear cell renal cell carcinoma (ccRCC) patients.

术前D-二聚体及纤维蛋白原含量与胃肠道间质瘤患者预后的关系

目的:探讨术前血浆D-二聚体(D-D)及纤维蛋白原含量(FIB)对胃肠道间质瘤(GIST)患者术后预后的预测价值。方法:收集2010年1月—2015年12月手术治疗的170例GIST患者临床病理及随访资料,分析术前D-D及FIB水平与患者预后的关系。结果:170例GIST患者中男91例,女79例;多见于50~70岁年龄段;肿瘤原发部位最常见于胃(122例,71.8%),其次为小肠(34例,20.0%)。全组术后3、5年无复发生存率(RFS)分别为85%、75%。以生存结局(出现转移或复发)为状态变量的ROC曲线显示,D-D与FIB的最佳截点值分别为1.24mg/L、3.24g/L。单因素分析显示,D-D≥1.24mg/L、FIB≥3.24g/L、NIH危险度分级中高危、肿瘤直径5cm及胃以外部位肿瘤均与GIST患者术后3、5年RFS降低有关(均P0.05);多因素分析显示,D-D(RR=0.382,95%CI=0.151~0.967,P=0.042)、FIB(RR=0.123,95%CI=0.035~0.430,P=0.001)、肿瘤NIH危险度分级(RR=0.149,95%CI=0.042~0.524,P=0.003)是影响GIST患者术后预后的独立危险因素。GIST患者NIH危险度分级与D-D、FIB之间均存在明显相关性(r=0.648、0.868,均P0.01)。结论:术前血浆D-D及FIB可作为预测GIST患者术后预后的参考指标。     

Serum beta 2 microglobulin levels in patients with renal cell carcinoma

Summary Serum B₂m concentrations were evaluated preoperatively in 40 patients with renal cell carcinoma and normal renal function, as assessed by serum creatinine <1.4 mg/dl, and compared with those of 23 age-matched controls. Mean value ± SD was 3,088±966 ng/ml for renal cancer patients, while controls had a value of 1,800±240 ng/ml. Statistical analysis, performed by Student t test, revealed a very high degree of significance (p<0.0005). No statistically significant differences were found between groups of patients classified according to tumor stage and cell type. Seventy percent of renal cell carcinoma cases had preoperatively elevated serum levels of B₂m.     

Evaluation of beta-blockers and survival among hypertensive patients with renal cell carcinoma

Objectives

Beta-blocker use is associated with improved survival for multiple nonurologic malignancies. Our objective was to evaluate the association between beta-blocker use and survival among surgically managed hypertensive patients with clear-cell renal cell carcinoma (ccRCC).

Normalization of C-reactive protein levels following cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors is associated with improved overall survival

Introduction and objectives

Pretreated C-reactive protein (CRP) has been suggested as one of the most important prognostic factors for metastatic renal cell carcinoma (mRCC). The aim of this study was to investigate the prognostic impact of the change in CRP level before and after cytoreductive nephrectomy (CN) in patients with mRCC treated with tyrosine kinase inhibitor.

Expression of cortactin and survivin in renal cell carcinoma associated with tumor aggressiveness

Purpose  We tested the hypothesis that the expression of cortactin and survivin in renal cell carcinomas (RCCs) correlates with more advanced stages of the disease. Methods  Immunohistochemical analysis of cortactin and survivin expression (scored on a scale of 0–400) was performed in 124 renal cell carcinomas including clear cell renal cell carcinoma (CRCC), papillary RCC (PRCC), CRCC with sarcomatoid differentiation (SRCC), chromophobe RCC (ChRCC), and CRCC with granular cell differentiation (GRCC). Results  Higher cortactin scores in CRCC were significantly correlated with higher T (p = 0.021) and N stages (p = 0.036), and nuclear grade (p = 0.012). Higher cortactin immunostaining scores were associated with higher mortality (p = 0.035). In addition, the survivin scores were significantly higher in the more aggressive GRCC and SRCC than in CRCC, suggesting a significant role of survivin expression in transformation of tumor cells to a more malignant phenotype. Conclusions  Higher expression of cortactin and survivin significantly correlated with advanced clinicopathological stage. Our findings support the potential targeting of survivin and cortactin for the development of novel therapeutic strategies for renal cell carcinoma.     

Elevated levels of serum aldolase A in patients with renal cell carcinoma

Summary To clarify whether serum aldolase A is a useful biomarker for renal cell carcinoma (RCC), we determined serum levels of the aldolase A isozyme by an enzyme immunoassay in patients suffering from RCC, other urological tumors, and benign urological diseases. Fortysix of 126 patients with RCC (37%) had elevated serum aldolase A. The positive rates were 23% in stage I, 40% in stage II, 63% in stage III, and 46% in stage IV. In 10 (83%) of 12 patients whose serum levels had been elevated preoperatively, these were reduced to within the normal range after nephrectomy. Four of 7 patients (57%) with progressive disease had elevated of aldolase A. In contrast, the positive rates were only 9.9% in 71 patients with other urological tumors and 5.8% in 52 cases of benign urological diseases. High concentrations of aldolase A isozyme in RCC tissues might be reflected in elevated serum levels. The present findings indicate that serum aldolase A is a useful biomarker for monitoring the clinical course of patients with RCC.     

A preoperative prognostic model for patients treated with nephrectomy for renal cell carcinoma

Background

Currently two pretreatment prognostic models with limited accuracy (65–67%) can be used to predict survival in patients with localized renal cell carcinoma (RCC).

Objective

We set out to develop a more accurate pretreatment model for predicting RCC-specific mortality after nephrectomy for all stages of RCC.

Design, setting, and participants

The data originated from a series of prospectively recorded contemporary cases of patients treated with radical or partial nephrectomy between 1984 and 2006. Model development was performed using data from 2474 patients from five centers and external validation was performed using data from 1972 patients from seven centers.

Measurements

The probability of RCC-specific mortality was modeled using Cox regression. The significance of the predictors was confirmed using competing risks analyses, which account for mortality from other causes.

Results and limitations

Median follow-up in patients who did not die of RCC-specific causes was 4.2 yr and 3.5 yr in the development and validation cohorts, respectively. The freedom from cancer-specific mortality rates in the nomogram development cohort were 75.4% at 5 yr after nephrectomy and 68.3% at 10 yr after nephrectomy. All variables except gender achieved independent predictor status. In the external validation cohort the nomogram predictions were 88.1% accurate at 1 yr, 86.8% accurate at 2 yr, 86.8% accurate at 5 yr, and 84.2% accurate at 10 yr.

Conclusions

Our model substantially exceeds the accuracy of the existing pretreatment models. Consequently, the proposed nomogram-based predictions may be used as benchmark data for pretreatment decision making in patients with various stages of RCC.     

Acetyl-CoA synthetase 2 enhances tumorigenesis and is indicative of a poor prognosis for patients with renal cell carcinoma

Background

Acetyl-CoA synthetase 2 (ACSS2) is highly expressed in various cancers, whereas ACSS2 expression and function in renal cell carcinoma (RCC) are unknown.

Development and characterization of clinically relevant tumor models from patients with renal cell carcinoma

Background

Animal models are instrumental in understanding disease pathophysiology and mechanisms of therapy action and resistance in vivo.

Objective

To establish and characterize a panel of mouse models of renal cell carcinoma (RCC) derived from patients undergoing radical nephrectomy.

Design, setting, and participants

In vivo and in vitro animal experiments.

Measurements

Tumor tissues obtained during surgery were implanted into the subcutaneous space of female BALB/c nude mice and serially passaged into new mice. Tumors were characterized by histology, short tandem repeat (STR) fingerprinting, von Hippel-Lindau (VHL) gene sequencing, and single nucleotide polymorphism (SNP) analysis. Tumor-bearing mice were treated with sunitinib or everolimus. Primary cell cultures were derived from patient tumors and transfected with a lentivirus carrying the luciferase gene. Four subcutaneous xenograft mouse models were developed, representing papillary type 1, papillary type 2, clear cell, and clear cell with sarcomatoid features RCC.

Results and limitations

RCC mouse models were established from four patients with distinct histologies of RCC. Tumor growth was dependent on histologic type, the size of the implanted tumor chip, and the passage number. Mouse tumors accurately represented their respective original patient tumors, as STR fingerprints were matching, histology was comparable, and SNP profiles and VHL mutation status were conserved with multiple passages. Bioluminescence imaging results were commensurate with subcutaneous xenograft growth patterns. Mice treated with sunitinib and everolimus exhibited an initial response, followed by a later stage of resistance to these agents, which mimics the clinical observations in patients with RCC.

Conclusions

We developed four mouse xenograft models of RCC with clear-cell and papillary histologies, with stable histologic and molecular characteristics. These models can be used to understand the basic biology of RCC as well as response and resistance to therapy.     

Low preoperative lymphocyte-monocyte ratio (LMR) represents a potentially poor prognostic factor in nonmetastatic clear cell renal cell carcinoma

ObjectivesTo explore the potential prognostic significance of the lymphocyte-monocyte ratio (LMR) in patients with nonmetastatic renal cell carcinoma (RCC), as the LMR has been repeatedly proposed to have a negative effect on patient?s survival in various hematological and solid cancers. However, findings about LMR?s prognostic significance in RCC have not been reported yet.Methods and materialsWe retrospectively evaluated the prognostic significance of the LMR in a cohort comprising 678 patients with nonmetastatic clear cell RCC, who were operated between 2000 and 2010 with curative radical or partial nephrectomy at a single tertiary academic center. Preoperative LMR was calculated 1 day before surgical intervention. Patients were categorized using an LMR cutoff of 3.0. Cancer-specific survival (CSS), metastasis-free survival, and overall survival were assessed using the Kaplan-Meier method. To evaluate the independent prognostic significance of the LMR, multivariate Cox regression models were applied. Additionally, the influence of the LMR on the predictive accuracy of the Leibovich prognosis score was determined using the Harrell concordance index (c-index) and decision curve analysis.ResultsLow LMR was statistically significantly associated with older patients (≥65 y), high tumor grade (G3+G4), advanced pathologic T category (pT3+pT4), the presence of histologic tumor necrosis, and male gender (P<0.05). Multivariate analysis identified a low LMR as an independent prognostic factor for patients? CSS (hazard ratio = 2.33; 95% CI: 1.10–4.94; P = 0.027). The estimated c-index was 0.83 using the Leibovich prognosis score and 0.86 when the LMR was added.ConclusionsRegarding CSS of patients with RCC, a decreased LMR represents an independent prognostic factor. Adding the LMR to well-established prognostic models, such as the Leibovich prognosis score, might improve their predictive ability.     

Preoperative nutritional status is an important predictor of survival in patients undergoing surgery for renal cell carcinoma

Background

The role of malnutrition has not been well studied in patients undergoing surgery for renal cell carcinoma (RCC).

Objective

Our aim was to evaluate whether nutritional deficiency (ND) is an important determinant of survival following surgery for RCC.

Design, setting, and participants

A total of 369 consecutive patients underwent surgery for locoregional RCC from 2003 to 2008. ND was defined as meeting one of the following criteria: body mass index <18.5 kg/m², albumin <3.5 g/dl, or preoperative weight loss ≥5% of body weight.

Intervention

All patients underwent radical or partial nephrectomy.

Measurements

Primary outcomes were overall and disease-specific mortality. Covariates included age, Charlson comorbidity index (CCI), preoperative anemia, tumor stage, Fuhrman grade, and lymph node status. Multivariate analysis was performed using a Cox proportional hazards model. Mortality rates were estimated using the Kaplan-Meier product-limit method.

Results and limitations

Eighty-five patients (23%) were categorized as ND. Three-year overall and disease-specific survival were 58.5% and 80.4% in the ND cohort compared with 85.4% and 94.7% in controls, respectively (p < 0.001). ND remained a significant predictor of overall mortality (hazard ratio [HR]: 2.41, 95% confidence interval [CI], 1.40–4.18) and disease-specific mortality (HR: 2.76; 95% CI, 1.17–6.50) after correcting for age, CCI, preoperative anemia, stage, grade, and nodal status. This study is limited by its retrospective nature.

Conclusions

ND is associated with higher mortality in patients undergoing surgery for locoregional RCC, independent of key clinical and pathologic factors. Given this mortality risk, it may be important to address nutritional status preoperatively and counsel patients appropriately.     

Loss of BAP1 expression in metastatic tumor tissue is an event of poor prognosis in patients with metastatic clear cell renal cell carcinoma

Purpose

To evaluate the prognostic impact of the protein expression of both PBRM1 and BAP1 in metastatic tissue of patients with metastatic clear cell renal cell carcinoma (ccRCC).

Early primary tumor size reduction is an independent predictor of improved overall survival in metastatic renal cell carcinoma patients treated with sunitinib

Background

In metastatic renal cell carcinoma (mRCC) patients treated with targeted agents and their primary tumor (PT) in situ, early PT decrease in size correlates with improved overall PT response, but the effect on overall survival (OS) is unknown.

Objective

To evaluate whether early PT size reduction is associated with improved OS in patients with mRCC undergoing treatment with sunitinib.

Design, setting, and participants

We reviewed the clinical and radiographic data of all mRCC patients seen at our institution between January 2004 and December 2009 without prior systemic treatment who received sunitinib with their PT in situ.

Measurements

Two independent reviewers measured the diameter of the PT and metastatic disease at baseline and subsequent scans to assess response. Early minor response was defined as ≥10% decrease within 60 d of treatment initiation. Univariate and multivariate analyses were used to calculate a hazard ratio (HR) corresponding to the risk of death based on clinical and pathologic factors as well as PT response.

Results and limitations

We identified 75 consecutive patients with a median follow-up of 15 mo. All patients were intermediate or poor risk by common risk stratification systems. Median initial PT diameter was 9.7 cm. Median maximum PT size reduction was −10.2% overall and −36.4% in patients who had early minor PT response.Median OS for patients without minor PT response, with minor PT response after 60 d, and with early minor PT response was 10.3, 16.5, and 30.2 mo, respectively. On multivariate analysis, early minor response was an independent predictor of improved OS (HR: 0.26; p = 0.031). Other significant predictors included venous thrombus, multiple bone metastases, lactate dehydrogenase above the upper limit of normal, symptoms at presentation, and more than two metastatic sites.

Conclusions

Early minor PT response is associated with improved OS. Future studies should evaluate this prognostic factor to identify patients with prolonged OS.     

肾透明细胞癌患者术前血清高敏C反应蛋白和降钙素原水平与肿瘤病理分期、分级的相关性研究

目的 探讨肾透明细胞癌(clear cell renal cell carcinoma,ccRCC)患者术前血清高敏C反应蛋白(high sensitive C-reactive protein,hs-CRP)和降钙素原(procalcitonin,PCT)水平与肿瘤病理分期、分级的相关性.方法 采用ELISA对2014年9月至2016年9月内蒙古医科大学附属医院泌尿外科收治的行肾癌根治术或肾部分切除术的98例ccRCC患者术前血清hs-CRP与PCT水平进行检测,并分析其与肿瘤病理分期、分级的相关性.结果 与病理分期为pT1[0.610(0.006~2.730)mg/L]及pT2[0.990(0.140~3.120)mg/L]的患者相比较,pT3+4患者的血清hs-CRP水平增高[1.510(0.070~3.940)mg/L],差异有统计学意义(P<0.05);与Fuhrman分级为Grade1~2组患者相比较,Grade3~4组患者血清hs-CRP水平增高[0.270(0.005~2.690)vs1.410(0.130~3.880)mg/L],差异有统计学意义(P<0.05).与病理分期为pT1[0.060(0.001~2.630)ng/ml]组患者相比较,pT2[0.420(0.023~1.550)ng/ml]和pT3+4[0.480(0.080~2.630)ng/ml]组患者的血清PCT水平增高,差异有统计学意义(P<0.05);与Fuhrman分级为Grade1~2的患者[0.050(0.001~1.220)ng/ml]相比较,Grade3~4[0.270(0.013~2.800)ng/ml]的患者其血清PCT水平增高,差异有统计学意义(P<0.05).受试者工作曲线分析结果表明,血清hs-CRP水平的阈值为0.652mg/L(灵敏度94.7%、特异性83.0%),血清PCT水平的阈值为0.086ng/ml(灵敏度82.1%、特异性80.5%).结论 ccRCC患者术前hs-CRP和PCT水平与肿瘤的病理分期、分级具有相关性.     

The loss of BAP1 protein expression predicts poor prognosis in patients with nonmetastatic clear cell renal cell carcinoma with inferior vena cava tumor thrombosis

Objectives

Renal cell carcinoma (RCC) is characterized by a propensity for extension into the renal vein and inferior vena cava (IVC) and is associated with poor prognosis. BAP1 mutation, which occurs in about 15% of patients with clear cell RCC (ccRCC), also predicts poor prognosis. The aim of this study was to elucidate the association between BAP1 protein expression and clinicopathological outcomes in patients with nonmetastatic ccRCC with an IVC tumor thrombus (IVCTT).

Activation of the kynurenine pathway predicts poor outcome in patients with clear cell renal cell carcinoma

Objective

To investigate the expression of the kynurenine (KYN) pathway components and the prognostic role of the KYN-to-tryptophan ratio (KTR) in a cohort of patients with clear cell renal cell carcinoma (ccRCC).