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Concept: Kidney cancer

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BACKGROUND: To evaluated the prognostic significance of the pre-operative C-reactive protein (CRP) serum level in patients with renal cell cancer (RCC). METHODS: We evaluated 1,161 RCC patients with complete patient and tumour specific characteristics as well as information about their pre-operative CRP-level, who had undergone either radical nephrectomy or nephron-sparing surgery at two German high-volume centres (University Hospitals of Hannover and Ulm). The mean follow-up was 54 months. RESULTS: The CRP-level, stratified to three subgroups (CRP <= 4, 4--10, and >10 mg/l), correlated significantly with tumour stage (p < 0.001), the risk of presenting nodal disease (2.1, 3.1, and 16.4%) and distant metastasis (2.9, 8.6, and 30.0%; p < 0.001). The Kaplan-Meier 5-year cancer specific survival (CSS) rates were 89.4, 77.9, and 49.5%, respectively (p < 0.001). Multivariate analysis identified CRP as an independent prognosticator for CSS as well as overall survival (p < 0.001). Patients with a CRP of 4--10 and >10 mg/l had a 1.67 and 2.48 fold higher risk of dying due to their RCC compared to those with a pre-operative CRP <=4 mg/l, respectively. CONCLUSIONS: A high preoperative serum CRP level is an independent predictor of poor survival in patients with RCC. Its routine use could allow better risk stratification and risk-adjusted follow-up of RCC patients.

Concepts: Cancer, Lung cancer, Cancer staging, C-reactive protein, Renin, Renal cell carcinoma, Nephrectomy, Kidney cancer

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Background: The objective of this meta-analysis was to evaluate the association between a history of kidney stones and kidney cancer. Methods: A literature search was performed from inception until June, 2014. Studies that reported odds ratios or hazard ratios comparing the risk of renal cell carcinoma (RCC) and transitional cell carcinoma of the upper urinary tract (TCC) in patients with the history of kidney stones versus those without the history of kidney stones were included. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. Result: Seven studies were included in our analysis to assess the association between a history of kidney stones and RCC. The pooled RR of RCC in patients with kidney stones was 1.76 (95% CI, 1.24 - 2.49). The subgroup analysis found that the history of kidney stones was associated with increased RCC risk only in males (RR, 1.41 [95% CI, 1.11 - 1.80]), but not in females (RR, 1.13 [95% CI, 0.86-1.49]). Five studies were selected to assess the association between a history of kidney stones and TCC. The pooled RR of TCC in patients with kidney stones was 2.14 (95% CI, 1.35 - 3.40). Conclusion: Our study demonstrates a significant increased risk of RCC and TCC in patients with prior kidney stones. However, the increased risk of RCC was noted only in male patients. This finding suggests that a history of kidney stones is associated with kidney cancer and may impact clinical management and cancer surveillance.

Concepts: Kidney, Male, Urinary bladder, Urinary system, Ureter, Renal pelvis, Renal cell carcinoma, Kidney cancer

4

Renal cell carcinoma (RCC) is a heterogeneous disease that is usually asymptomatic until late in the disease. There is an urgent need for RCC specific biomarkers that may be exploited clinically for diagnostic and prognostic purposes. Preoperative fasting urine and serum samples were collected from patients with clinical renal masses and assessed with ¹H NMR and GCMS (gas chromatography-mass spectrometry) based metabolomics and multivariate statistical analysis. Alterations in levels of glycolytic and tricarboxylic acid (TCA) cycle intermediates were detected in RCC relative to benign masses. Orthogonal Partial Least Square Discriminant Analysis plots discriminated between benign vs. pT1 (R2 = 0.46, Q2 = 0.28; AUC = 0.83), benign vs. pT3 (R2 = 0.58, Q2 = 0.37; AUC = 0.87) for ¹H NMR-analyzed serum and between benign vs. pT1 (R2 = 0.50, Q2 = 0.37; AUC = 0.83), benign vs. pT3 (R2 = 0.72, Q2 = 0.68, AUC = 0.98) for urine samples. Separation was observed between benign vs. pT3 (R2 = 0.63, Q2 = 0.48; AUC = 0.93), pT1 vs. pT3 (R2 = 0.70, Q2 = 0.54) for GCMS-analyzed serum and between benign vs. pT3 (R2Y = 0.87; Q2 = 0.70; AUC = 0.98) for urine samples. This pilot study suggests that urine and serum metabolomics may be useful in differentiating benign renal tumors from RCC and for staging RCC.

Concepts: Kidney, Cancer, Statistics, Lung cancer, Multivariate statistics, Analysis, Renal cell carcinoma, Kidney cancer

2

Kidney cancer represents about 5% of all new cancer diagnoses. The most common form of kidney cancer arises from renal epithelium, named renal cell carcinoma (RCC). This entity comprises different histological and molecular subtypes. Unraveling the molecular biology and cytogenetic of RCC has enabled the development of several targeted agents that have improved treatment outcomes of these patients. This article reviews all the agents currently approved for the treatment of RCC, and discuss upcoming molecules. Mechanism of action, preclinical and clinical development and ongoing trials, are presented for each agent, providing a broad vision of the current state of targeted therapy in RCC and possible future developments.

Concepts: DNA, Cancer, Biology, Renal pelvis, Renin, Renal cell carcinoma, Nephrectomy, Kidney cancer

1

Clear cell Renal Cell Carcinoma (ccRCC) represents the most common kidney cancer worldwide. Increased cell proliferation associated with abnormal microRNA (miRNA) regulation are hallmarks of carcinogenesis. Ankyrin repeat and single KH domain 1 (ANKHD1) is a highly conserved protein found to interact with core cancer pathways in Drosophila, however its involvement in RCC is completely unexplored. Quantitative PCR studies coupled with large-scale genomics data analyses demonstrated that ANKHD1 is significantly upregulated in kidneys of RCC patients when compared to healthy controls. Cell cycle analyses revealed that ANKHD1 is an essential factor for RCC cell division. To understand the molecular mechanism(s) utilized by ANKHD1 to drive RCC cell proliferation we performed bioinformatics analyses which revealed that ANKHD1 contains a putative miRNA-binding motif. We screened 48 miRNAs with tumour-enhancing or suppressing activities, and found that ANKHD1 binds to and regulates three tumour-suppressing miRNAs (i.e. miR-29a, miR-205, and miR-196a). RNA-immunoprecipitation assays demonstrated that ANKHD1 physically interacts with its target miRNAs via a single K-Homology (KH)-domain, located in the c-terminus of the protein. Functionally we discovered that ANKHD1 positively drives ccRCC cell mitosis via binding to and suppressing mainly miR-29a and to a lesser degree via miR-196a/205, leading to an upregulation in pro-proliferative genes such as CCDN1. Collectively, these data identify ANKHD1 as a new regulator of ccRCC proliferation via specific miRNA interactions.

Concepts: Gene, Cancer, Cell division, Cell cycle, DNA replication, Mitosis, Renal cell carcinoma, Kidney cancer

1

Patients with metastatic renal carcinoma (mRCC) treated with first-line pazopanib were not included in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model. SPAZO (NCT02282579) was a nation-wide retrospective observational study designed to assess the effectiveness and validate the IMDC prognostic model in patients treated with first-line pazopanib in clinical practice.

Concepts: Clinical trial, Lung cancer, Observational study, Validation, Renin, Renal cell carcinoma, Nephrectomy, Kidney cancer

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With this review, we describe the most recent advances in active surveillance as well as diagnosis and management of small renal masses (SRMs).

Concepts: Cancer staging, Renal pelvis, Kidney cancer, Most recent common ancestor

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To assess the diagnostic ability of a pixel intensity-based analysis in evaluating the magnetic resonance imaging characteristics of small renal masses, especially in differentiating fat-poor angiomyolipoma from renal cell carcinoma.

Concepts: Spin, Nuclear magnetic resonance, Types of cancer, Magnetic resonance imaging, Squamous cell carcinoma, Voxel, Renal cell carcinoma, Kidney cancer

0

Renal cell carcinoma (RCC) is the most common form of kidney cancer. While cure remains exceptionally infrequent in RCC patients with systemic or recurrent disease, current targeted molecular strategies, including multi-targeted tyrosine kinase inhibitors (TKIs), notably changed the treatment paradigm of advanced renal cancer. Yet, complete and durable responses have been noted in only a few cases. Our studies reveal that sunitinib triggers two resistance-promoting signaling pathways in RCC cells, which emanate from the endoplasmic reticulum (ER) stress response: a PERK-driven ER stress response that induces expression of the pro-tumorigenic cytokines IL-6, IL-8, and TNF-α, and a TRAF2-mediated NF-κB survival program that protects tumor cells against cell death. PERK blockade completely prevents sunitinib-induced expression of IL-6, IL-8 and TNF-α, whereas NF-κB inhibition reinstates sensitivity of RCC cells to sunitinib both in vitro and in vivo. Taken together, our findings indicate that ER stress response may contribute to sunitinib resistance in RCC patients.

Concepts: Gene, Cancer, Signal transduction, Endoplasmic reticulum, In vitro, Renal pelvis, Renal cell carcinoma, Kidney cancer

0

The purpose of this study was to evaluate CT criteria for achieving high positive predictive value (PPV) for renal cell carcinoma (RCC) in patients with solid small renal masses (SRMs) less than 4 cm without macroscopic fat.

Concepts: Glucose, Mass, Renal cell carcinoma, Kidney cancer