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Computed Tomography (CT) is widely used in oncology for morphological evaluation and diagnosis, commonly through visual assessments, often exploiting semi-automatic tools as well. Well-established automatic methods for quantitative imaging offer the opportunity to enrich the radiologist interpretation with a large number of radiomic features, which need to be highly reproducible to be used reliably in clinical practice. This study investigates feature reproducibility against noise, varying resolutions and segmentations (achieved by perturbing the regions of interest), in a CT dataset with heterogeneous voxel size of 98 renal cell carcinomas (RCCs) and 93 contralateral normal kidneys (CK). In particular, first order (FO) and second order texture features based on both 2D and 3D grey level co-occurrence matrices (GLCMs) were considered. Moreover, this study carries out a comparative analysis of three of the most commonly used interpolation methods, which need to be selected before any resampling procedure. Results showed that the Lanczos interpolation is the most effective at preserving original information in resampling, where the median slice resolution coupled with the native slice spacing allows the best reproducibility, with 94.6% and 87.7% of features, in RCC and CK, respectively. GLCMs show their maximum reproducibility when used at short distances. [ABSTRACT FROM AUTHOR]

Background/Aim: Programmed death ligand-1 (PD-L1) and programmed death protein 1 (PD-1) expression levels in many tumors and their correlation with prognosis have been actively studied. However, studies on PD-1 expression and its prognostic value in clear cell renal cell carcinoma (ccRCC) are limited and controversial. In this study, we describe the expression of PD-1 and its prognostic significance and association with clinical features in patients with ccRCC. Materials and Methods: We obtained clinicopathological data from 166 patients with ccRCC who were treated at Gyeongsang National University Hospital, Jinju, Korea between January 2000 and December 2009. Tissue microarray blocks were made using representative paraffin blocks of ccRCC specimens. Two pathologists analyzed PD-L1 and PD-1 expression in both tumor and inflammatory cells. Results: PD-1 expression in tumor-infiltrating inflammatory cells was significantly correlated with unfavorable disease-free survival (DFS) (p<0.001) and disease-specific survival (DSS) (p=0.002) in the univariate analysis. A statistically significant correlation between PD-1 expression and unfavorable DFS (p=0.025) was observed in the multivariate analysis. Conclusion: PD-1 expression in tumor-infiltrating inflammatory cells serves as an independent prognostic factor for unfavorable DSS in patients with ccRCC. [ABSTRACT FROM AUTHOR]

About a third of patients with kidney cancer experience recurrence or cancer-related progression. Clinically, kidney cancer prognoses may be quite different, even in patients with kidney cancer at the same clinical stage. Therefore, there is an urgent need to screen for kidney cancer prognosis biomarkers. Differentially expressed genes (DEGs) were identified using kidney cancer RNA sequencing data from the Gene Expression Omnibus (GEO) database. Biomarkers were screened using random forest (RF) and support vector machine (SVM) models, and a multigene signature was constructed using the least absolute shrinkage and selection operator (LASSO) regression analysis. Univariate and multivariate Cox regression analyses were performed to explore the relationships between clinical features and prognosis. Finally, the reliability and clinical applicability of the model were validated, and relationships with biological pathways were identified. Western blots were also performed to evaluate gene expression. A total of 50 DEGs were obtained by intersecting the RF and SVM models. A seven-gene signature (RNASET2, EZH2, FXYD5, KIF18A, NAT8, CDCA7, and WNT7B) was constructed by LASSO regression. Univariate and multivariate Cox regression analyses showed that the seven-gene signature was an independent prognostic factor for kidney cancer. Finally, a predictive nomogram was established in The Cancer Genome Atlas (TCGA) cohort and validated internally. In tumor tissue, RNASET2 and FXYD5 were highly expressed and NAT8 was lowly expressed at the protein and transcription levels. This model could complement the clinicopathological characteristics of kidney cancer and promote the personalized management of patients with kidney cancer. [ABSTRACT FROM AUTHOR]

Brain metastases can contribute to a decreased quality of life for patients with cancer, often leading to malaise, neurologic dysfunction, or death. Intracerebral hemorrhage (ICH) is an especially feared complication in patients with brain metastases given the potential for significant morbidity and mortality. We aim to characterize patients with cancer and brain metastases admitted to hospitals nationwide and identify factors associated with ICH. The 2016 Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP-NIS) was queried for all patients with cancer hospitalized with a diagnosis of brain metastases. Admissions with a primary or secondary diagnosis of ICH were further identified. Baseline differences in demographic, clinical, socioeconomic, and hospital-related characteristics between patients with and without ICH were assessed by chi-square, Mann–Whitney U, and ANOVA testing. Multivariable logistic regression was used to identify factors associated with ICH. Weighted frequencies were used to create national estimates for all data analysis. In 2016, a total 145,225 hospitalizations were associated with brain metastases, of which 4,145 (2.85%) had a concurrent diagnosis of ICH. Patients with ICH were more likely to have a longer length of stay (median 5 days vs 4 days, p < 0.001) and a higher cost of stay (median $14,241.14 vs $10,472.54, p < 0.001). ICH was found to be positively associated with having a diagnosis of melanoma (odds ratio [OR] 5.01; 95% Confidence Interval [CI] 3.50–7.61) and kidney cancer (OR 2.50; 95% CI 1.69–3.72). Patients on long-term anticoagulation had a higher risk of ICH (OR 1.49; CI 1.15–1.91). Approximately 3% of patients hospitalized with brain metastases also had a diagnosis of ICH, which was significantly associated with longer length of stay and cost. Patients with melanoma, kidney cancer, and on long-term anticoagulation had a higher risk of ICH. Physicians should consider the risks of anticoagulation carefully for patients with brain metastases, especially those with melanoma and kidney cancer. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNA) are frequently dysregulated in clear cell renal cell carcinoma (ccRCC). Objective: This study aimed to elucidate the role of miRNA expression patterns in renal carcinogenesis and to identify the specific miRNAs that exhibit expression patterns closely associated with patient outcomes. Methods: We examined the expression patterns of selected miRNAs, including miRNA-155-5p, miRNA-122-5p, miRNA-21-5p, miRNA-185-5p, miRNA-106a-5p, miRNA-106b-3p, miRNA-34b-3p, miRNA-210-3p, miRNA-141-3p, miRNA-200c-3p, miRNA-135a-5p, miRNA-30a-5p, miRNA-218-5p, miRNA-429, miRNA-200a-3p and miRNA-200b-3p, in 96 samples of ccRCCs using the TaqMan real-time PCR method. In addition, cluster analysis was performed to stratify expression patterns of multiple miRNAs. Results: In the present study, three distinct subgroups could be clearly stratified in ccRCCs. Subgroup 1 was characterized by upregulation of miRNA-155-5p, miRNA-122-5p, miRNA-21-5p, miRNA-185-5p, miRNA-106a-5p, miRNA-106b-3p, miRNA-34b-3p and miRNA-210-3p. Subgroup 2 was closely associated with downregulation of miRNA-141-3p, miRNA200c-3p, miRNA-30a-5p, miRNA-218-5p, miRNA-429, miRNA-200a-3p and miRNA-200b-3p. Moreover, significant lower expression of miRNA-135a-5p was a distinctive feature of subgroup 3, which was correlated with metachronous metastasis. Among the individual markers in subgroup 3, miRNA-135a-5p was retained in multivariate analysis. The cutoff value of miRNA-135a-5p expression to identify the association of an altered level of miRNA-135a-5p with metachronous metastasis in ccRCCs was determined and showed excellent specificity. Conclusion: We suggest that the expression pattern of the chosen miRNAs is useful to identify renal carcinogenesis and to help identify the association of such expression patterns with metachronous metastasis in ccRCCs. In addition, miRNA-135a-5p was an excellent marker for prediction of metachronous metastasis. [ABSTRACT FROM AUTHOR]

Abstract Newer treatment strategy based on proliferative nuclear marker Ki-67 targeted therapy holds promise for prioritized/personalized treatment options with regard to improved survival and outcome in patients with renal cancer. Over the past decade, the importance of Ki-67 in prognosis of breast cancer has been widely studied, however very few studies and literatures are available in the context of renal cancer which has an increasing incidence internationally. The focus of this present review is to fill the gaps pertaining to its prognosis and management with newly understood mechanisms of targeted interventions. Recent breakthrough discoveries have highlighted the correlation of Ki-67 expression to stage and metastatic potential in renal tumours. A better understanding of molecular structure and different protein domains along with its regulation will provide evidence for precise target thereby controlling the proliferation rate correlated with decrease in the Ki-67 protein levels. Therapies targeting Ki-67 is still in the preclinical stage, besides its diagnostic and/or prognostic significance, a better understanding of targeted strategical studies is required for extrapolation to the clinical use. Current understanding of the associated molecular pathways and the precise role of Ki-67 could streamline the basis for predicting renal cancer outcome. Highlights • Ki-67 act as good molecular surrogate of the aggressive behaviour exhibited by tumours. • Ki-67 has been used as standalone marker for indicating prognosis in renal cancer. • Ki-67 labelling index as determined by immunohistochemistry (IHC) analysis is indicative of patient outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Aim of this study was to develop a multi-gene signature to help better predict prognosis for stage III renal cell carcinoma (RCC) patients. Methods: Fourteen pairs of stage III tumor and normal tissues mRNA expression data from GSE53757 and 16 pairs mRNA expression data from TCGA clear cell RCC database were used to analyze differentially expressed genes between tumor and normal tissues. Common different expressed genes in both datasets were used for further modeling. Lasso Cox regression analysis was performed to select and build prognostic multi-gene signature in TCGA stage III kidney cancer patients (N = 122). Then, the multi-gene signature was validated in stage III renal cancer cases in Fudan University Shanghai Cancer Center (N = 77). C-index and time-dependent ROC were used to test the efficiency of this signature in predicting overall survival. Results: In total, 1,370 common different expressed genes were found between tumor and normal tissues in both datasets. After Lasso Cox modeling, nine mRNAs were finally identified to build a classifier. Using this classifier, we could classify stage III clear cell RCC patients into high-risk group and low-risk group. Prognosis was significantly different between these groups in discovery TCGA cohort, validation FUSCC cohort and entire set (All P < 0.001). Multivariate cox regression in entire set (N = 199) revealed that risk group classified by 9-gene signature, age of diagnosis, pN stage and ISUP grade were independent prognostic factor of overall survival in stage III kidney cancer patients. Conclusion: We developed a robust multi-gene classifier that can effectively classify stage III RCC patients into groups with low and high risk of poor prognosis. This signature may help select high-risk patients who require more aggressive adjuvant target therapy or immune therapy. [ABSTRACT FROM AUTHOR]

Purpose: Patients with localised renal cell carcinoma (RCC) can expect excellent oncologic outcomes. As such, there has been a shift towards maximising health-related quality of life (HRQoL). A greater understanding of HRQoL outcomes associated with different treatment options for RCC can facilitate patient-centred care, shared decision-making and enable cost utility analyses to guide health policies. The aim of this literature review was to evaluate the evidence regarding HRQoL following different management strategies for localised RCC.Methods: Three databases were searched to identify studies reporting HRQoL in patients with localised renal cancer, including Medline, the Tuft's Medical Centre Cost Effectiveness Analysis registry and the EuroQol website.Results: Considerable methodological heterogeneity was noted. Laparoscopic nephrectomy was associated with significantly better short-term physical function compared to open surgery, although the effect on mental function was inconclusive. Nephron-sparing surgery was associated with better physical function compared to radical surgery. Patients' perception of remaining renal function was a significant independent predictor of HRQoL, rather than surgery type. Tumour size, stage, post-operative complications, age, body mass index, occupational status, educational level and comorbidities were significant predictors of HRQoL. Only three studies were available regarding non-surgical management options and very little data were available regarding the impact of follow-up protocols and long-term effects of "cancer survivorship."Conclusion: There is a need for validated and reproducible RCC-specific HRQoL instruments and standardisation amongst studies to enable comparisons. Increased awareness regarding determinants of poor HRQoL may enable high-risk patients to receive tailored support. [ABSTRACT FROM AUTHOR]

Objective: This study was aimed to investigate the characteristics of multi-slice spiral computed tomography (CT) image in kidney cancer patients and its clinical value in staging diagnosis of kidney cancer.Materials and Methods: This study included 57 patients who were confirmed as kidney cancer through postoperative pathological examination; they were diagnosed within February 2014 and December 2016 in our hospital. The data obtained from multi-slice spiral CT plain scan and contrast-enhanced CT of these patients was retrospectively analyzed. Moreover, we determined the characteristics of multi-slice spiral CT image for kidney cancer and analyzed their consistency with pathological staging.Results: CT plain scan showed that kidney lumps were mostly found in the prominent renal contour or renal parenchyma, and they were round-like or round in shape. Among the 57 included patients, the tumors of 43 cases showed regular edges, and 14 showed irregular edges. Among the 14 cases, 10 patients had tumors with lobulated edges and 5 with spinous tumor edge. Among all the 57 patients, CT plain scan showed there were 5 cases with slightly higher density, 24 cases with mixed density, 28 cases with equal density or slightly lower density. The range of tumor diameter was 2.1-12.6 cm; the tumor diameter was smaller than 3 cm in 11 cases, 3-7 cm in 34 cases, and larger than 7 cm in 12 cases. In terms of contrast enhancement, the arterial phase was obviously enhanced in 31 cases, moderately and irregularly enhanced in 18 cases, and slightly enhanced in 8 cases. Moreover, the renal parenchymal scan showed a rapid decline in the enhancement and a further decline in the enhancement of renal pelvic tumor; the three stages of enhancement could be expressed in terms of fast forwardness and fast backwardness. A total of 33, 4, 9, and 11 cases were classified as postoperative pathological Stage I, II, III, and IV, respectively; 35, 5, 7, and 10 cases were classified as CT scan Stage I, II, III, and IV, respectively; and 34, 5, 8, and 10 cases were classified as contrast-enhanced CT scan Stage I, II, III, and IV, respectively. No significant difference was observed in the frequency of CT scan, the enhanced stage and pathological stage (P > 0.05).Conclusion: CT image of kidney cancer revealed the morphological and enhanced features of this tumor. The consistency between CT stage and pathological stage was high; thus, this method can be applied as a forecasting method for pathological staging. [ABSTRACT FROM AUTHOR]

Onconephrology is a rapidly evolving subspeciality that covers all areas of renal involvement in cancer patients. The complexity of the field may benefit from well-defined multidisciplinary management administered by a dedicated team. Since there is an increasing need to address the needs of this population in dedicated outpatient clinics, it is critical to highlight basic characteristics and to suggest areas of development. In this brief perspective article, we analyse the requirements of an onconephrology clinic in terms of logistics, critical mass of patients and building a multidisciplinary team. We will further discuss which patients to refer and which conditions to treat. The last part of the article is dedicated to education and performance indicators and to analysis of the potential advantages of applying the hub-and-spoke model to this field. The ultimate aim of this experience-based article is to initiate debate about what an onconephrology outpatient clinic might look like in order to ensure the highest quality of care for this growing population of patients. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of hospital volume on outcomes of robot-assisted partial nephrectomy (RAPN). Materials and Methods: Patients with renal cell carcinoma who underwent RAPN between 2010 and 2013 were identified in the National Cancer Database. Hospital yearly RAPN volume was categorized into groups by sorting patients as closely as possible into five groups of equal size (quintiles): very low; low; medium; high; and very high volume. Outcomes included 30-day mortality, 90-day mortality, open conversion, prolonged length of hospital stay (PLOS; defined as >3 days), 30-day readmission rate, and positive surgical margin (PSM) rate. Unadjusted analyses and multivariable logistic regressions were used to compare outcomes. Sensitivity analyses with hospital volume considered as a continuous variable were also performed. Results: A total of 18 724 RAPN cases were included. Hospital volume quintiles were: very low volume, 1-7 cases (n = 3 693); low volume, 8-14 cases (n = 3 719); medium volume, 15-23 cases (n = 3 833); high volume, 24-43 cases (n = 3 649); and very high volume, =44 cases (n = 3 830). There was no significant difference in 30-day or 90-day mortality among the five groups. Multivariable logistic regression analysis (reference: very low volume) showed that higher hospital volume was associated with lower odds of conversion (low [odds ratio {OR}: 0.88; P = 0.377]; medium [OR: 0.60; P = 0.001]; high [OR: 0.57; P < 0.001]; very high [OR: 0.47; P < 0.001]), lower odds of PLOS (low [OR: 0.93; P = 0.197], medium [OR: 0.75; P < 0.001]; high [OR: 0.62; P < 0.001]; very high [OR: 0.45; P < 0.001]), and lower odds of PSMs (low [OR: 0.76; P < 0.001]; medium [OR: 0.76, P < 0.001]; high [OR: 0.59; P < 0.001]; very high [OR: 0.34; P < 0.001]). Sensitivity analyses confirmed increasing hospital volume (per 1-case increase) was associated with lower odds of conversion (OR: 0.986; P < 0.001), PLOS (OR: 0.989; P < 0.001) and PSMs (OR: 0.984; P < 0.001). A difference in 30-day readmission rate was found in unadjusted analysis but not in adjusted analyses. Conclusion: Undergoing RAPN at higher-volume hospitals may have better peri-operative outcomes (conversion to open and LOS) and lower PSM rates. Future studies are needed to explore the detailed components that lead to the superior outcomes in higher-volume hospitals. [ABSTRACT FROM AUTHOR]

Objectives: To assess the epidemiological and histopathological profile of renal tumors in three medical units in Kinshasa. Material and methods We performed a retrospective and descriptive cross-sectional study including 42 cases of renal tumors diagnosed in Kinshasa University Hospital, the National Institute of Biomedical Research (INRB) and the Lomo Medical Center between 1990 and 2012. Results: Our study showed that kidney tumors accounted for 0.5% of all tumors while cancers were the most common with 83.3% (35/42 cases). Nephroblastoma (45.2%) was the most common and followed by renal cell carcinoma (38.1%). The median age of onset of nephroblastoma was 3.5 years (7 months - 15 years), while it was 53 years (33-69 years) for clear cell carcinoma. Angiomyolipoma and papillary carcinoma were predominantly female whereas nephroblastoma, clear cell carcinoma, and Oncocytoma was predominantly male. The distribution of renal cell carcinoma by Fürhman nuclear grade showed a predominance of grade 3 (37.5%). Conclusions: Renal tumors accounted for 0.5% of all tumors with nephroblastoma at the top with 3.5 years (7 months to 15 years) as median age. We noted a female predominance for angiomyolipoma and papillary carcinoma, whereas nephroblastoma, clear cell carcinoma, and oncocytoma were predominantly male. [ABSTRACT FROM AUTHOR]

Since the introduction of molecular targeted agents for the treatment of metastatic renal cell cancer (mRCC), several treatment outcomes, including those from our facilities, have been reported. However, the outcome of these drugs, classified by the metastatic organs, is not well known. The present study reported the treatment results of molecular-targeted agents as classified by the metastatic organ at Osaka City University Graduate School of Medicine. A total of 180 consecutively treated patients who had received molecular targeted agents for metastatic renal cancer for 3 or more months were retrospectively analyzed. The overall survival was calculated and compared according to the Memorial Sloan-Kettering Cancer Center (MSKCC) criteria, the number of metastatic organs, and metastatic lesions. The median overall survival of patients with mRCC treated by molecular targeted agents was 34 months. A significant difference in survival rate between groups was found according to the MSKCC criteria. Patients with single metastatic organ lived significantly longer compared with those with metastases in multiple organs. Patients with pancreatic metastasis had a good response to molecular targeted drugs. Pancreatic metastasis, the number of metastatic organs, and MSKCC criteria were independent risk factors for overall survival. Treatment of mRCC by molecularly targeted agents did not show any difference by metastatic organs except for the pancreas, although its efficacy depends on the number of metastatic organs and the MSKCC classification. [ABSTRACT FROM AUTHOR]

This article is co-authored by a patient with advanced renal cell carcinoma and his treating oncologist. The patient relates his personal experiences in struggling with cancer, including physical limitations, but also details his psychological, existential and spiritual distress through the cancer journey. The patient shares a proactive approach to the most common side effects of therapy. The professional reflects on the rapid development of new therapy options; the implications for clinical practice by the management of long-tem therapy; how to deal with patient expectations; and the management of patient distress as an integrated part of the contemporary approach for treating kidney cancer. [ABSTRACT FROM AUTHOR]

Background Kidney cancer is one of the most common cancers in the USA causing 14,400 deaths per year. The phosphatase and tensin homolog (PTEN) has been extensively documented as a tumor suppresser gene in cancer. However, there is unclear evidence for its clinicopathological and prognostic role in kidney cancer. Methods A systematic review of literature assessing PTEN expression and clinical outcome in patients with kidney cancer. Web of Science, PubMed, Embase, and Chinese databases were searched for collecting for the eligible studies providing sufficient information. Pooled odds ratios (ORs) and hazard ratios (HRs) were respectively used to evaluate the association between PTEN levels and the clinicopathological features and clinical outcomes. Results A total of 35 studies enrolling 4532 patients were finally included in this study. For the survival outcome, the result suggested that shorter overall survival (OS) was correlated with low PTEN expression (HR = 0.57, 95% CIs: 0.45–0.74, P < 0.0001). The meta-analysis indicated a significantly increased risk of tumorigenesis in the PTEN low-level group relative to the control group (OR = 0.098, 95% CIs: 0.067–0.143, P < 0.001). Moreover, the results displayed the positive correlation between poorer differentiation (OR = 0.234, 95% CIs: 0.133–0.410, P < 0.001), distant metastasis (OR = 0.179, 95% CIs: 0.092–0.350, P = 0.001), lymph node metastasis (OR = 0.252, 95% CIs: 0.113–0.563, P < 0.001), advanced clinical stages (OR = 0.233, 95% CI: 0.133, 0.406, P < 0.001) and low PTEN expression. Finally, there was no obvious publication bias found in the meta-analysis. Conclusions Decreased PTEN was associated with poorer survival outcomes of patients with kidney cancer and PTEN acts as a tumor suppressor in tumorigeneses and progression in kidney cancer. [ABSTRACT FROM AUTHOR]

Background: Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominantly inherited cancer predisposition syndrome associated with an increased risk of spontaneous pneumothorax (SP) and renal cell carcinoma in the adult population. Recent studies suggest that BHD accounts for up to 10% of all SP in adults and BHD in children with SP have been reported. Methods: To explore to what extent BHD is the cause of childhood pneumothorax, we studied a Danish BHD cohort consisting of 109 cases from 22 families. Clinical data was gathered by review of medical records. A systematic literature search concerning childhood and adolescence pneumothorax in BHD was performed and identified publications reviewed. Results: In our cohort, three of 109 BHD cases experienced childhood pneumothorax, corresponding to a prevalence of 3%. Reviewing the literature, data regarding more than 800 BHD cases were covered. Only seven previously published cases of childhood pneumothorax in BHD were identified. Conclusion: Our findings suggest that BHD is likely the cause of a larger subset of childhood pneumothoraces than hitherto recognized. Awareness of BHD as a cause of childhood pneumothorax needs to be raised to provide patients and relatives with the possibility of specialized management of SP and regular renal cancer surveillance. [ABSTRACT FROM AUTHOR]

Background: Birt-Hogg-Dubé syndrome is an autosomal dominant hereditary condition caused by mutations in the folliculin-encoding gene FLCN (NM_144997). It is associated with skin lesions such as fibrofolliculoma, acrochordon and trichodiscoma; pulmonary lesions including spontaneous pneumothorax and pulmonary cysts and renal cancer. Methods: Genomic DNA was extracted from peripheral venous blood samples of the propositi and their family members. Genetic analysis was performed by whole exome sequencing and Sanger sequencing aiming at corresponding exons in FLCN gene to explore the genetic mutations of these two families. Results: In this study, we performed genetic analysis by whole exome sequencing and Sanger sequencing aiming at corresponding exons in FLCN gene to explore the genetic mutations in two Chinese families. Patients from family 1 mostly suffered from pneumothorax and pulmonary cysts, several of whom also mentioned skin lesions or kidney lesions. While in family 2, only thoracic lesions were found in the patients, without any other clinical manifestations. Two FLCN mutations have been identified: One is an insertion mutation (c.1579_1580insA/p.R527Xfs on exon 14) previously reported in three Asian families (one mainland family and two Taiwanese families); while the other is a firstly reviewed mutation in Asian population (c.649C > T / p.Gln217X on exon 7) that ever been detected in a French family. Conclusions: Overall, The detection of these two mutations expands the spectrum of FLCN mutations and will provide insight into genetic diagnosis and counseling of Birt-Hogg-Dubé syndrome. [ABSTRACT FROM AUTHOR]

In our previous study we found altered expression of 19 adhesion-related genes in renal tumors. In this study we hypothesized that disturbed expression of adhesion-related genes could be caused by microRNAs: short, non-coding RNAs that regulate gene expression. Here, we found that expression of 24 microRNAs predicted to target adhesion-related genes was disturbed in renal tumors and correlated with expression of their predicted targets. miR-25-3p, miR-30a-5p, miR-328 and miR-363-3p directly targeted adhesion-related genes, including COL5A1, COL11A1, ITGA5, MMP16 and THBS2. miR-363-3p and miR-328 inhibited proliferation of renal cancer cells, while miR-25-3p inhibited adhesion, promoted proliferation and migration of renal cancer cells. TGF-β1 influenced the expression of miR-25-3p, miR-30a-5p, and miR-328. The analyzed microRNAs, their target genes and TGF-β1 formed a network of strong correlations in tissue samples from renal cancer patients. The expression signature of microRNAs linked with TGF-β1 levels correlated with poor survival of renal cancer patients. The results of our study suggest that TGF-β1 coordinates the expression of microRNA network that regulates cellular adhesion in cancer. [ABSTRACT FROM AUTHOR]

Objective: To assess the readability and comprehensibility of web-based German-language patient education material (PEM) issued by urological associations. Materials and Methods: German PEM available in June 2017 was obtained from the European Association of Urology (EAU), German (DGU), Swiss (SGU) and Austrian (ÖGU) Association of Urology websites. Each educational text was analyzed separately using 4 well-established readability assessment tools: the Amstad Test (AT), G-SMOG (SMOG), Wiener Sachtextformel (WS) and the Lesbarkeitsindex (LIX). Results: The EAU has issued PEM on 8 topics, the DGU 22 and the SGU 5. The ÖGU refers to the PEMs published by the DGU. Calculation of grade levels (SMOG, WS, LIX) showed readability scores of the 7th-14th grades. The easiest readability was found for materials on Nocturia and Urinary Incontinence issued by the EAU. Kidney Cancer and Infertility, issued by the DGU had the hardest readability. The EAU achieved the best median AT score, followed by the SGU, and the DGU. Conclusion: Remarkable differences between readability were found for the PEMs issued by EAU, DGU and SGU. Materials published by the EAU were the easiest to read. Improving the readability of certain PEMs is of crucial importance to meet patient needs and act in the interests of a growing, self-informing German-speaking patient community. [ABSTRACT FROM AUTHOR]

Objective: To assess the usefulness of tumor-centered multiplanar reconstruction (TC-MPR) for predicting intraoperative urinary collecting system (UCS) entry in patients with peripheral renal tumors undergoing partial nephrectomy (PN). Methods: Dynamic computed tomography images of 50 peripheral cT1 renal tumors treated with laparoendoscopic PN were analyzed. TC-MPR generated a digital crosssectional image showing the tumor center and the closest calyx on a same plane. Patients and tumor characteristics including the distance from the tumor margin to the closest calyx (MPR-distance), and the angle formed by 2 tangent lines from the closest calyx to the tumor (MPR-angle) were assessed. Results: Intraoperative UCS entry was observed in 15 patients (30%). The patients who experienced intraoperative UCS entry had a higher RENAL score, wider MPR-angle, and shorter MPR-distance than those who did not (p = 0.04, p = 0.001, p < 0.001, respectively). Multivariate analysis identified MPR-angle as an independent factor for intraoperative UCS entry (p < 0.001). Conclusions: The spatial information assessed using TC-MPR serves as a predictive factor for intraoperative UCS entry during PN. [ABSTRACT FROM AUTHOR]

Long noncoding RNA (lncRNA) antisense noncoding RNA in the INK4 locus (ANRIL) is involved in several human cancers. However, the role of ANRIL in renal cell carcinoma (RCC) remains unclear. This study aimed to explore whether, and how, ANRIL affects the progression of RCC. First, the expression of ANRIL in clinical tumor tissues and four kinds of RCC cell lines was evaluated. After transfection, cell viability, colony number, apoptosis, migration, and invasion were assessed. The expression of proteins related to apoptosis, epithelial-to-mesenchymal transition (EMT), and the β-catenin signaling pathway was then assessed. In addition, the effect of IWR-endo (β-catenin inhibitor) on cell viability, migration, and invasion, as well as β-catenin expression, was also evaluated. The results showed that ANRIL was highly expressed in RCC tissues and RCC cell lines. ANRIL significantly promoted cell proliferation, migration, invasion, and EMT but inhibited cell apoptosis. Additionally, the expression levels of β-catenin, Ki-67, glycogen synthase kinase 3β (GSK-3β), phosphorylated GSK-3β, T-cell transcription factor 4 (TCF-4), and leukemia enhancer factor 1 (LEF-1) were all markedly upregulated by ANRIL. The effect of ARNIL silencing was opposite to that of ANRIL overexpression. The effect of ARNIL on proliferation, migration, and invasion of RCC cells was found to be reversed by IWRendo. In conclusion, ANRIL, which is highly expressed in RCC, acted as a carcinogen in RCC cells through the activation of the β-catenin pathway. [ABSTRACT FROM AUTHOR]

The formation of a complex between Ga(III) and morin (3,5,7,2′,4′-pentahydroxyflavone) was studied. UV–visible, infrared and mass spectroscopies were used to characterize the complex. The stoichiometric ratio for the reaction between metal ion and flavonoid was determined using the methods of Yoe–Jones and Job, which confirmed that a 1:1 Ga–morin complex was formed (estimated binding constant = 2.31 × 104 l mol−1). It was found that the coordination to Ga(III) occurs through the carbonyl oxygen atom and the 3-OH group of the morin molecule. According to developed conditions, complexation reaction with 68Ga was performed and the complex was used to label kidney cancer cells (CAKI-1, CAKI-2, ACHN and 786-O). The knowledge gained from this study should be useful for the development of new radiopharmaceuticals for diagnostic purposes containing 68Ga. [ABSTRACT FROM AUTHOR]

It is critically important to define disease-specific research priorities to better allocate limited resources. There is growing recognition of the value of involving patients and caregivers, as well as expert clinicians in this process. To our knowledge, this has not been done this way for kidney cancer. Using the transparent and inclusive process established by the James Lind Alliance, the Kidney Cancer Research Network of Canada (KCRNC) sponsored a collaborative consensus-based priority-setting partnership (PSP) to identify research priorities in the management of kidney cancer. The final result was identification of 10 research priorities for kidney cancer, which are discussed in the context of current initiatives and gaps in knowledge. This process provided a systematic and effective way to collaboratively establish research priorities with patients, caregivers, and clinicians, and provides a valuable resource for researchers and funding agencies. [ABSTRACT FROM AUTHOR]

Lipidomic analysis of biological samples in a clinical research represents challenging task for analytical methods given by the large number of samples and their extreme complexity. In this work, we compare direct infusion (DI) and chromatography – mass spectrometry (MS) lipidomic approaches represented by three analytical methods in terms of comprehensiveness, sample throughput, and validation results for the lipidomic analysis of biological samples represented by tumor tissue, surrounding normal tissue, plasma, and erythrocytes of kidney cancer patients. Methods are compared in one laboratory using the identical analytical protocol to ensure comparable conditions. Ultrahigh-performance liquid chromatography/MS (UHPLC/MS) method in hydrophilic interaction liquid chromatography mode and DI-MS method are used for this comparison as the most widely used methods for the lipidomic analysis together with ultrahigh-performance supercritical fluid chromatography/MS (UHPSFC/MS) method showing promising results in metabolomics analyses. The nontargeted analysis of pooled samples is performed using all tested methods and 610 lipid species within 23 lipid classes are identified. DI method provides the most comprehensive results due to identification of some polar lipid classes, which are not identified by UHPLC and UHPSFC methods. On the other hand, UHPSFC method provides an excellent sensitivity for less polar lipid classes and the highest sample throughput within 10 min method time. The sample consumption of DI method is 125 times higher than for other methods, while only 40 μL of organic solvent is used for one sample analysis compared to 3.5 mL and 4.9 mL in case of UHPLC and UHPSFC methods, respectively. Methods are validated for the quantitative lipidomic analysis of plasma samples with one internal standard for each lipid class. Results show applicability of all tested methods for the lipidomic analysis of biological samples depending on the analysis requirements. [ABSTRACT FROM AUTHOR]

Acute renal failure can be the result of acute renal cortical necrosis (RCN), which commonly occurs from complications occurring during pregnancy. RCN is rarely caused by medications, although tranexamic acid, which is used in patients with acute bleeding for its antifibrinolytic effects, reportedly causes acute RCN in rare cases. An 82-year-old woman experienced gastrointestinal bleeding after endoscopic papillectomy of an ampullary adenoma. The bleeding was controlled with tranexamic acid administration; however, 4 days later, her urine volume decreased and she developed pulmonary edema and dyspnea. Serum creatinine levels increased from 0.8 to 3.9 mg/dL and dialysis was performed. Abdominal pelvic computed tomography with contrast enhancement revealed bilateral RCN with no renal cortex enhancement. Renal dysfunction and oliguria persisted and hemodialysis was continued. Clinicians must be aware that acute RCN can occur after tranexamic acid administration to control bleeding. [ABSTRACT FROM AUTHOR]

Objective: To examine the effect that neoadjuvant axitinib for the treatment of localized renal cell carcinoma has on body compartment composition.Materials and Methods: The study was based on a single-institution, single-arm clinical trial that enrolled 24 patients with locally advanced non-metastatic biopsy-proven clear cell renal cell carcinoma. Patients received axitinib orally for up to 12 weeks. Computed tomography scans were completed before the start of treatment, after 7 weeks of treatment and at the completion of 12 weeks of treatment. Patients underwent nephrectomy after axitinib treatment. The primary outcome of the current study was change in body compartment composition. Secondary outcomes included development of new-onset sarcopenia and changes in body weight.Results: A total of 23 patients had a complete set of imaging for evaluation, of which 19 (82.6%) lost weight. Median weight loss was 4.5 kg (P <.001). Seven patients (30.4%) had sarcopenia before treatment, with an additional 5 (21.7%) developing sarcopenia during treatment. Median decrease in skeletal muscle was 2.9 cm2/m2 (P <.001), visceral adipose tissue was 4.9 cm2/m2 (P = .132), and subcutaneous adipose tissue was 1.0 cm2/m2 (P = .043). Ten of the 16 patients (62.5%) without baseline sarcopenia achieved a partial response, whereas only 1 of the 7 patients (14.3%) with baseline pretreatment sarcopenia achieved a partial response (P = .069).Conclusion: Neoadjuvant axitinib resulted in a decrease in skeletal muscle and subcutaneous adipose tissue, as well as weight loss. Patients with baseline sarcopenia tended to have a lower response rate to neoadjuvant axitinib. [ABSTRACT FROM AUTHOR]

Background. For potential transplant recipients with a prior history of renal malignancy, no evidence-based recommendations currently exist with regard to waiting duration on dialysis. We aim to improve decision making by evaluating the impact of waiting duration on the outcomes of kidney cancer patients awaiting renal transplantation. Methods. The United States Renal Data System was used to identify patients with a known cause of end-stage renal disease (ESRD) from 1983 to 2007. Evaluation of overall survival (OS) was performed with Kaplan-Meier estimates and Cox proportional hazards models. Fine-Gray competing risk models were used to assess cancer-specific mortality (CSM) and non-cancerspecificmortality (NCSM). Results. Of 1 374 175 patients with ESRD, 228 984 (16.7%) received transplantation. Transplant recipients with renal malignancy-associated ESRD (RM-ESRD) had longer waiting durations than those with other known causes of ESRD (2.4 versus 1.3 years; P<0.0001). RM-ESRD patients who had shorter waiting durations (0-2 years) had better OS than those who waited longer (2+ years) (10-year OS 69.0 versus 46.7%, respectively; P<0.0001), with similar CSM (10-year CSM 10.3 versus 10.2%, respectively; P=0.883), whereas NCSM was worse for those with longer waiting durations (10-year NCSM 20.7 versus 44.3%, respectively; P<0.0001). On Cox modeling, the status of RM-ESRD was not a significant predictor (P=0.07), while longer waiting duration remained significant (P<0.0001). Conclusion. We found that CSM was not affected by waiting duration, while NCSM significantly improved with shorter wait times. These findings suggest that the OS of potential transplant recipients with RM-ESRD may be improved by reducing waiting duration. [ABSTRACT FROM AUTHOR]

Objectives To characterize the extent to which geriatric and related healthcare services are provided to older adults undergoing surgery for kidney cancer, a potential growth area in geriatrics and oncology. Design Population-based observational study. Setting Surveillance, Epidemiology, and End Results cancer data linked with Medicare claims. Participants Adults aged 65 and older with kidney cancer treated surgically from 2000 to 2009 (N = 19,129). Measurements Receipt of geriatric consultation, medical comanagement during the surgical hospitalization, inpatient physical or occupational therapy ( PT/ OT), and postacute PT/ OT during the surgical care episode. Multivariable, mixed-effects models were used to identify associated participant and hospital characteristics, examine trends over time, and characterize hospital-level variation. Results Geriatric consultation occurred rarely in the perioperative period (2.6%). Medical comanagement (15.8%), inpatient PT/ OT (34.2%), and postacute PT/ OT (15.6%) occurred more frequently. In our mixed-effects models, participant age and comorbidity burden appeared to be consistent determinants of use of services, although hospital-level variation was also noted ( P < .001). Use of geriatric consultation increased modestly in the latter years of the study period ( P < .05). In contrast, medical comanagement (183%), inpatient PT/ OT (73%), and postacute PT/ OT (71%) increased substantially over the study period ( P < .001). Conclusion Although geriatric consultation remained sparse, use of medical comanagement and rehabilitation services has grown considerably for older adults undergoing surgery for kidney cancer. Efforts to reorganize cancer and surgery care should explore reasons for variation and the potential for these service elements to meet the health needs of an aging population. [ABSTRACT FROM AUTHOR]

In this presentation we will bring to your attention the case of a patient with clear cell renal carcinoma and the disease extended by multiple pulmonary, lymphatic, bone and liver metastases, classified according to the prognostic criteria in the intermediate risk group. The patient benefited from right nephrectomy with right partial adrenalectomy followed by four consecutive targeted therapies for metastatic disease: two lines of tyrosine kinase inhibitors (sunitinib in the first line and sorafenib in the second line), followed by two lines of mTOR inhibitors (temsirolimus and everolimus). The monitoring of disease progression was performed periodically through clinical and paraclinical examinations, computed tomography, bone scan and MRI examinations. The therapeutic line was changed every time the disease progressed. We experienced a spectacular patient survival under four treatment lines of 45 months in metastatic disease, compared to a statistically estimated median survival period of 22.5 months for patients with metastatic renal cancer in the intermediate risk group. We basically observed that for this patient the survival was double. [ABSTRACT FROM AUTHOR]

Introduction. P.A.D.U.A. (The preoperative aspects and dimensions used for anatomic), R.E.N.A.L. (radius exophytic/endophytic nearness anterior/posterior location) and zonal NePhRO scoring were developed in an effort to predict the intraoperative (warm time ischemia, blood loss) and postoperative complications in patients undergoing partial nephrectomy, with an important role on surgical decision-making (2-4). Materials and methods. Between January 2014 and July 2017, 37 patients(p) underwent retroperitoneoscopic nephro-sparing surgery at our center for clinically localized renal tumor. All patients had a normal contralateral kidney. The selection of patients for nephro-sparing surgery was based on preoperative CT scan, location of the tumor, the individual general health status of the patient and individual surgeon preferences. A chart review was carried out, including age, sex, anatomic preoperative scoring system (P.A.D.U.A., R.E.N.A.L. nephrometry and zonal NePhRO), operative time (skin opening to skin closing), estimated blood loss (EBL), warm ischemia time (WIT), hospital stay. Results. The mean age of patients with partial nephrectomy was 54.3±9.1 years. Mean preoperative serum creatinine level for the patient group was 0.97±0.14 mg/dl. All patients had normal contralateral kidney. Average tumor diameter in this group was 3.6± 0.86 cm. When using P.A.D.U.A. score to predict warm time ischemia p value was of 0.001, even if the mean warm ischemia time is higher in medium risk patients than in high risk patients 24.3 min vs. 23.2 min. R.E.N.A.L. nephrometry score was able to predict the warm ischemia time according to the risk groups (17.6 vs. 23.9 vs. 31 min) with a p value under 0.001. Zonal NePhRO score was statistically correlated with total operative time, blood loss, warm ischemia and renal function decrease, all with a p value < 0.05. Conclusion. P.A.D.U.A. score, R.E.N.A.L. nephrometry score and Zonal NePhRO score have proved to be reliable preoperative tools in order to evaluate surgical complexity and to predict outcomes such as warm time ischemia, blood loss, postoperative estimated GFR and complications rate. [ABSTRACT FROM AUTHOR]

Purpose: The study aimed to compare the diagnostic efficiency of contrast-enhanced ultrasound (CEUS) with that of contrast-enhanced computed tomography (CECT) in the evaluation of benign and malignant small renal masses (SRMs) (<4 cm) confirmed by pathology. Methods: A total of 118 patients with 118 renal masses smaller than 4 cm diagnosed by both CEUS and CECT were enrolled in this study, including 25 benign lesions and 93 malignant lesions. All lesions were confirmed by histopathologic diagnosis after surgical resection. The diagnostic imaging studies of the patients were retrospectively reviewed by two independent ultrasonologists and two independent radiologists blinded to the CT or ultrasound findings and final histological results. All lesions on both CEUS and CECT were independently scored on a 3-point scale (1: benign, 2: equivocal, and 3: malignant). The concordance between interobserver agreement was interpreted using a weighted kappa statistic. The diagnostic efficiency of the evaluation of benign and malignant lesions was compared between CEUS and CECT. Results: All the 118 included lesions were detected by both CEUS and CECT. In CEUS and CECT imaging evaluation of the 118 lesions, the weighted kappa value interpreting the concordance between interobserver agreement was 0.89 (95% CI 0.79-0.98) and 0.93 (95% CI 0.87-0.99), respectively. Both CEUS and CECT demonstrated good diagnostic performance in differential diagnosis of benign and malignant SRMs with sensitivity of 93.5% and 89.2%, specificity of 68% and 76%, PPV of 91.6% and 93.3%, NPV of 73.9% and 65.5%, and AUC of 0.808 and 0.826, respectively. There was no statistically significant difference in any of the diagnostic performance indices between these two methods ( P > 0.05). However, the qualitative diagnosis of small papillary renal cell carcinoma (RCC) by CEUS was significantly better than that by CECT ( P < 0.05), while there was no significant difference in qualitative diagnostic accuracy on other histotypes of SRMs between CEUS and CECT ( P > 0.05). Conclusions: Both CEUS and CECT imaging modalities are effective for the differential diagnosis of benign and malignant SRMs. Furthermore, CEUS may be more effective than CECT for the qualitative diagnosis of small papillary RCC. [ABSTRACT FROM AUTHOR]

Introduction: Variables, such as smoking and obesity, are rarely available in administrative databases. We explored the added value of including these data in an administrative database study evaluating the association of statin use with survival in kidney cancer. Methods: We linked administrative data with chart-abstracted data on smoking and obesity for 808 patients undergoing nephrectomy for kidney cancer. Base models consisted of variables from administrative databases (age, sex, year of surgery, and different measures of comorbidity [to compare their sensitivity to smoking and obesity data]); extended models added chart-abstracted data. We compared coefficients for statin use with overall (OS) and cancerspecific survival (CSS), and used the c-statistic and net reclassification improvement (NRI) to compare predications of five-year survival obtained from Cox proportional hazard models. Results: The coefficient for statin use changed minimally following addition of abstracted data (<6% for OS, <2% for CSS). Base models performed similarly for OS, with c-statistics of 0.75 (95% confidence interval [CI] 0.72-0.79) for Charlson score and 0.73 (95% CI 0.69-0.78) for John Hopkins Aggregated Diagnosis Groups score. After including abstracted data, c-statistics modestly improved (change <0.02); CSS demonstrated similar findings. NRIs were 0.210 (95% CI 0.062-0.297) and 0.186 (-0.031-0.387) when using the Charlson score, and 0.207 (0.068-0.287) and 0.197 (0.007-0.399) when using the Aggregated Diagnosis Groups score, for OS and CSS, respectively. Conclusions: The inclusion of data on smoking and obesity marginally influences survival models in kidney cancer studies using administrative data. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to determine the serum levels of angiopoietin-like 4 (ANGPTL4) in patients with renal cell carcinoma (RCC) and explore its potential as a biomarker.Materials and Methods: Blood samples were taken from 110 patients with RCC, 66 healthy controls, and patients with other solid tumors. Serum ANGPTL4 levels were measured using the enzyme-linked immunosorbent assay, and their correlation with clinical characteristics was further analyzed. Received operating characteristic (ROC) curves, Kaplan-Meier curves, and log-rank analyses were used to evaluate diagnostic and prognostic significance.Results: Serum ANGPTL4 levels were significantly higher in patients with RCC compared with healthy controls and patients with other types of cancers (P<0.0001) and associated with sex, Fuhrman grades, metastasis states, and tumor node metastasis stages (P<0.05), but not with age, tumor size, and histological types (P>0.05). The ROCs/area under the ROC curve analysis indicated an area under the ROC curve of 0.844 (sensitivity = 0.691; specificity = 0.939) and 0.725 (sensitivity = 0.909; specificity = 0.568), respectively, to distinguish patients with RCC from healthy controls and those with metastasis from those without metastasis. The survival analysis revealed that patients with low serum ANGPTL4 had longer progression-free survival compared with those with high serum ANGPTL4 (P = 0.033).Conclusion: The present study suggested that the elevated serum ANGPTL4 level might be a novel diagnostic and prognostic biomarker for patients with RCC. [ABSTRACT FROM AUTHOR]

It is unclear whether cancer-related epidemiology after kidney transplantation is translatable between countries. In this population-cohort study, we compared cancer incidence and all-cause mortality after extracting data for every kidney-alone transplant procedure performed in England and New York State ( NYS) between 2003 and 2013. Data were analyzed for 18,493 and 11,602 adult recipients from England and NYS respectively, with median follow up 6.3 years and 5.5 years respectively (up to December 2014). English patients were more likely to have previous cancer at time of transplantation compared to NYS patients (5.6% vs. 3.5%, P < 0.001). Kidney allograft recipients in England versus NYS had increased cancer incidence (12.3% vs. 5.9%, P < 0.001) but lower all-cause mortality during the immediate postoperative stay (0.7% vs. 1.0%, P = 0.011), after 30-days (0.9% vs. 1.8%, P < 0.001) and after 1-year post-transplantation (3.0% vs. 5.1%, P < 0.001). However, mortality rates among patients developing post-transplant cancer were equivalent between the two countries. During the first year of follow up, if patients had an admission with a cancer diagnosis, they were more likely to die in both England (Odds Ratio 4.28 [95% CI: 3.09-5.93], P < 0.001) and NYS (Odds Ratio 2.88 [95% CI: 1.70-4.89], P < 0.001). Kidney allograft recipients in NYS demonstrated higher hazard ratios for developing kidney transplant rejection/failure compared to England on Cox regression analysis. Our analysis demonstrates significant differences in cancer-related epidemiology between kidney allograft recipients in England versus NYS, suggesting caution in translating post-transplant cancer epidemiology between countries. [ABSTRACT FROM AUTHOR]

Stearoyl-CoA desaturase 1 (SCD1), the rate-limiting enzymes in the biosynthesis of monounsaturated fatty acids from saturated fatty acids, have been gradually recognized as a potential therapeutic target for various malignancies, particularly in clear-cell renal cell carcinoma (ccRCC). However, the prognostic value of SCD1 in ccRCC is still unknown. The aim of this study is to evaluate the clinical significance of SCD1 expression in patients with ccRCC. SCD1 expression in tumor tissues obtained from 359 patients who underwent nephrectomy for ccRCC are retrospectively assessed. During a median follow-up of 63 months (range: 1–144month), 56 patients in total died before the last follow-up in this study. Survival curves were plotted with the Kaplan–Meier method and compared with the log-rank test. Meanwhile, univariate and multivariate Cox regression models were applied to evaluate the prognostic value of SCD1 expression in overall survival (OS) for ccRCC patients. Moreover, SCD1 was enrolled into a newly built nomogram with factors selected by multivariate analysis, and the calibration was built to evaluate the predictive accuracy of nomogram. High SCD1 expression occurred in 61.6% (221/359) of ccRCC patients, which was significantly associated with age (p = 0.030), TNM stage (p = 0.021), pN stage (p = 0.014), Fuhrman grade (p = 0.014) and tumor sizes (p = 0.040). In multivariate analysis, SCD1 expression was confirmed as an adverse independent prognostic factor for OS. The prognostic accuracy of TNM stage, Fuhrman grade and tumor sizes was significantly increased when SCD1 expression was added. The independent prognostic factors, pT stage, pN stage, Fuhrman grade and tumor sizes, as well as SCD1 expression were integrated to establish a predictive nomogram with high predictive accuracy. Calibration curves revealed optimal consistency between observations and prognosis. In conclusion, high SCD1 expression is an independent prognostic factor for OS in patients with ccRCC. Our data suggest that the expression of SCD1 might guide the clinical decisions for patients with ccRCC. [ABSTRACT FROM AUTHOR]

Background: Molecular intratumour heterogeneity (ITH) is common in clear cell renal carcinomas (ccRCCs). However, it remains unknown whether this is mirrored by heterogeneity of drug responses between metastases in the same patient. Methods: We performed a retrospective central radiological analysis of patients with treatment-naïve metastatic ccRCC receiving anti-angiogenic tyrosine kinase inhibitors (TKIs) (sunitinib or pazopanib) within three similar phase II trials. Treatment was briefly interrupted for cytoreductive nephrectomy. All patients had multiple metastases that were measured by regular computed tomography scans from baseline until Response Evaluation Criteria In Solid Tumours (RECIST)-defined progression. Each metastasis was categorised as responding, stable or progressing. Patients were classed as having a homogeneous response if all lesions were of the same response category and a heterogeneous response if they differed. Results: A total of 115 metastases were assessed longitudinally in 27 patients. Of these patients, 56% had a heterogeneous response. Progression occurred through the appearance of new metastases in 67%, through progression of existing lesions in 11% and by both in 22% of patients. Despite RECIST-defined progression, 57% of existing metastases remained controlled. The sum of controlled lesions was greater than that of uncontrolled lesions in 47% of patients who progressed only with measurable new lesions. Conclusions: We identified frequent ITH of anti-angiogenic TKI responses, with subsets of metastases responding and progressing within individual patients. This mirrors molecular ITH and may indicate that anti-angiogenic drug resistance is confined to subclones and not encoded on the trunk of the tumours' phylogenetic trees. This is clinically important, as patients with small-volume progression may benefit from drug continuation. Predominant progression with new rather than in existing metastases supports a change in disease biology through anti-angiogenics. The results highlight limitations of RECIST in heterogeneous cancers, which may influence clinical trial data validity. This analysis requires prospective confirmation. [ABSTRACT FROM AUTHOR]

Objective:The aim of this study was to investigate the influence of age at diagnosis on tumor characteristics and cancer-specific survival (CSS) in renal cell carcinoma (RCC). Materials and methods:Data of patients who underwent radical or partial nephrectomy for renal tumor between 2003 and 2011 at multiple institutions were collected. Patients were divided into two groups according to age at diagnosis: 20–39 years and 40–79 years. To adjust for potential baseline confounders, propensity score matching was performed. Results:All included data showed that young RCC patients presented with renal tumors that had a more favorable histological subtype, were localized, smaller in size, and had a lower Fuhrman nuclear grade. The 5 year CSS rates were 95.5% and 90.5% in the young and old patient groups, respectively (log rankp = 0.019). After matching on the propensity score, the two groups with RCC had 302 patients each. Because the groups were matched on covariates, there were no significant differences in the pathological proportion, tumor size, Fuhrman nuclear grade and clinical T stage. The 5 year CSS rates were 95.5% and 94.7% in the young and old patient groups, respectively (log rankp = 0.184). Conclusion:After adjusting for potential biases, there was no significant difference in prognosis between young and old patients with RCC. [ABSTRACT FROM PUBLISHER]

Objectives: The aim of this study was to investigate the clinical usefulness for prediction of outcome of laparoscopic partial nephrectomy (LPN) using the R.E.N.A.L nephrometry scoring system (RNS) and centrality index score (C-index).Materials and Methods: We retrospectively reviewed 64 patients who underwent LPN from 2010 to 2014 in our institution. The RNS and C-index scores were assigned according to the described protocols for their systems. The relationships between the patients' scores before surgery and the outcomes of LPN, warm ischemia time (WIT), operative time (ORT), estimated blood loss (EBL), and percent change in estimated glomerular filtration rate (eGFR) were analyzed retrospectively.Results: Mean tumor size was 3.1 cm, mean WIT was 27.6 minutes, mean ORT was 189.0 minutes, and mean EBL was 187 mL. Although the RNS had statistically significant correlations with WIT, ORT, and percent change in eGFR, these correlations were not score-dependent. For WIT, a statistically significant difference was observed between the low-risk group and the middle-risk group. For percent change in eGFR, a statistically significant difference was observed between the low-risk group and the high-risk group only. For the C-index, statistically significant correlations between complexity categories and WIT, ORT, EBL, and percent change in eGFR were observed. Regarding the raw C-index scores, linear correlations were observed between the scores and each outcome of LPN.Conclusions: The RNS and C-index are useful for predicting the complexity of LPN. The C-index may be more suitable than the RNS for predicting postoperative renal function. [ABSTRACT FROM AUTHOR]

Aim of the database: The main purpose of the database of the Danish Renal Cancer Group (DaRenCaData) is to improve the quality of renal cancer treatment in Denmark and secondarily to conduct observational research. Study population: DaRenCaData includes all Danish patients with a first-time diagnosis of renal cancer in the Danish National Pathology Registry since August 1, 2010. Main variables: DaRenCaData holds data on demographic characteristics, treatments, and pathology collected through linkage to central registries and online registration of a few clinical key variables. Eight quality indicators have been selected for monitoring treatment quality and outcome after renal cancer. Descriptive data: The incidence of renal cancer in Denmark has increased from 12.7 per 100,000 population-years in 2010--2011 to 15.9 per 100,000 population-years in 2014-2015. A total of 3,977 Danish patients with renal cancer have been enrolled in the database in the period August 1, 2010-July 31, 2015. The completeness of data registration has increased substantially since the first years of the database. A tendency toward smaller and less advanced tumors, less invasive surgery, and a shorter hospital stay was observed, while the postoperative morbidity and mortality remained stable. Concurrently, the 1-year survival has improved and was 84.1% in 2014-2015. Conclusion: DaRenCaData provides valuable information on quality of and outcome after renal cancer treatment. Efforts to improve collection and registration of data are ongoing. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of disseminated cancer on perioperative outcomes following radical nephrectomy.Methods: We conducted a retrospective cohort study of patients undergoing radical nephrectomy for kidney cancer from 2005 to 2014 using the American College of Surgeons National Surgical Quality Improvement Program, a multi-institutional prospective registry that captures perioperative surgical complications. Patients were stratified according to the presence (n = 657) or absence (n = 7143) of disseminated cancer at the time of surgery. We examined major complications (death, reoperation, cardiac event, or neurologic event) within 30 days of surgery. Secondary outcomes included pulmonary, infectious, venous thromboembolic, and bleeding complications; prolonged length of stay; and concomitant procedures (bowel, liver, spleen, pancreas, and vascular procedures). Adjusted odds ratio (aOR) and 95% confidence interval (95% CI) were calculated using multivariate logical regression models.Results: Patients with disseminated cancer were older and more likely to be male, have greater comorbidities, and have undergone open surgery. Major complications were more common among patients with disseminated cancer (7.8%) than those without disseminated cancer (3.2%; aOR 2.01, 95% CI 1.46-2.86). Mortality was significantly higher in patients with disseminated cancer (3.2%) than those without disseminated cancer (0.5%; P < .0001). Pulmonary (aOR 1.68, 95% CI 1.09-2.59), thromboembolic (aOR 1.72, 95% CI 1.01-2.96), and bleeding complications (aOR 2.12, 95% CI 1.73-2.60) were more common among patients with disseminated cancer as was prolonged length of stay (aOR 1.27, 95% CI 1.06-1.53).Conclusion: Nephrectomy in patients with disseminated cancer is a morbid operation with significant perioperative mortality. These data may be used for preoperative counseling of patients undergoing cytoreductive nephrectomy. [ABSTRACT FROM AUTHOR]

Objective: To estimate the incidence rates of kidney-related clinical outcomes among patients with tuberous sclerosis complex (TSC)-related angiomyolipoma (AML) compared to an age-matched control cohort in the United States.Materials and Methods: This was a retrospective, observational study. Administrative data from the MarketScan Research Databases were used to select patients with TSC and renal AML. An age-matched group with no TSC or renal AML was identified for comparison. Outcomes were incidence rates per 100 patient-years and number of months to development of hematuria, chronic kidney disease, renal hemorrhage, kidney failure, and inpatient death.Results: Among the commercially insured TSC-renal AML patients (N = 605) and matched controls (N = 1815), 37.2% were <18 years old. Among Medicaid TSC-renal AML patients (N = 246) and matched controls (N = 738), 38.6% were aged <18. In the commercial sample, in both age groups (<18 and ≥18), the incidence rate of each clinical outcome measured was higher in the TSC-renal AML cohort than in the control cohort, with several differences reaching statistical significance. Compared with younger patients, older TSC-renal AML patients had higher incidence rates of clinical outcomes (hematuria: 20.4 vs 8.7; chronic kidney disease: 9.6 vs 3.5; renal hemorrhage 2.7 vs 0.7; kidney failure: 1.9 vs 0.4) and took less time on average to develop each clinical outcome. A similar pattern of results was observed among patients with Medicaid insurance.Conclusion: TSC-renal AML patients are at significantly higher risk for renal morbidity relative to the general population. [ABSTRACT FROM AUTHOR]

Background: Adequate prediction of survival plays an important role in treatment decisions for patients with spinal bone metastases (SBM). Several prognostic factors are already used in daily clinical practice, but factors related to stability of SBM are still unknown. Therefore, we designed this study to identify these prognostic factors.Methods: We retrospectively assessed 915 patients from solid tumors with commonly metastased into the bone treated at our department between January 2000 and January 2012. Lung cancer (NSCLC), breast and renal cancer listed in Table 1 are the most common solid tumors with bone metastasis in this study. Prostate carcinoma was excluded due to osteoblastic SBM with no influence for stability. We calculated overall survival (OS) and bone survival (BS; time between first diagnosis of bone metastases until death) with the Kaplan-Meier method and assessed prognostic factors for BS with the log-rank test and a Cox regression model separately for patients with stable and unstable SBM.Results: Median follow-up was 9.3 months. OS after 6 months, 1, 2, and 5 years was 81, 62, 42, and 25 % in patients with stable SBM and 78, 57, 38, and 22 % in patients with unstable SBM (p = 0.851). BS was 57, 38, 22, and 5 % in the group of stable SBM after 6 months, 1, 2, and 5 years. For patients with unstable SBM BS after 6 months, 1, 2, and 5 years was 59, 39, 19, and 8 % (p = 0.755). In multivariate analysis we found male gender (HR = 1.27 [95 % CI 1.01-1.60], p = 0.04), Karnofsky performance status (KPS) <80 % (HR = 1.27 [95%CI 1.04-1.55], p = 0.02) and non-small cell lung cancer (NSCLC; HR = 2.77 [95%CI 1.99-3.86], p < 0.0001) to be independent prognostic factors for shortened survival in patients with stable SBM. Independent prognostic factors for unstable SBM were age per year (HR = 1.01 [95 % CI 1.0-1.02], p = 0.025), multiple SBM (HR = 1.35 [95 % CI 1.1-1.65], p = 0.003), and NSCLC (HR = 2.0 [95 % CI 1.43-2.80], p < 0.0001). Additionally, not wearing an orthopedic corset (HR = 0.77 [95 % CI 0.62-0.96], p = 0.02) was associated with prolonged BS in patients with unstable SBM and in both groups BS was significantly longer in patients without liver metastases (stable SBM: HR = 0.72 [95 % CI 0.56-0.92], p = 0.008; unstable SBM: HR = 0.71 [95 % CI 0.54-0.92], p = 0.01).Conclusions: Survival was equal for patients with stable and unstable SBM. However, prognostic factors differed in both groups and stability should therefore be considered in treatment decision-making. [ABSTRACT FROM AUTHOR]

Tubulocystic renal cell carcinoma (TCRCC) is a recently described rare subtype of RCC. To best of our knowledge less than 70 cases have been reported till date. The concurrent papillary RCC (PRCC) and TCRCC has been documented in literature, but the co-occurrence of clear cell RCC (CCRCC) and TCRCC is very rare. We are describing a rare case of incidentally detected TCRCC occurring with CCRCC in a 45 years old male who presented with high grade fever with chills and rigors. Grossly, there were two distinct tumors in the total nephrectomy specimen. The larger tumor displayed the histopathological features of CCRCC and the smaller tumor revealed the features of TCRCC.treatment in the present case. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the current indications and surgical and survival outcomes for cryoablation (CA) using either a percutaneous (PCA) or a laparoscopic approach (LCA). We also investigated the ability of the PADUA score to predict the risk of complications and local recurrence. Methods: A retrospective analysis was performed at two European tertiary referral centers. Parameters analyzed included size, location, approach, operative time, hospital stay, complications, and functional and oncologic outcomes. Univariate and multivariate analyses were performed. An ROC analysis was conducted to evaluate the accuracy of the PADUA score. Results: Eighty patients were included. Mean tumor size was 2.6 cm. PCA was more often performed in posterior (95 vs. 60 %), inferior (72 vs. 32 %), and lateral (87 vs. 55 %) tumors. The global complication rate was 8.75 %, although proximity to the renal sinus resulted in a higher rate (30 vs. 4 %). Mean follow-up was 34 and 23 months for LCA and PCA, respectively. The 5-year recurrence-free survival was 76 and 90 % for LCA and PCA, respectively. Multivariate analysis showed that tumor involvement of the collecting system was predictive of recurrence. Under ROC analysis, PADUA score was a mild predictor for complications (AUC = 0.601) and a good predictor for recurrence (AUC = 0.723); PADUA ≥8 was identified as a cutoff for patients to a higher risk of recurrence. Conclusions: The percutaneous approach is confirmed to be the preferred CA technique for posterior and lateral tumors. CA in deeper renal lesions and tumors with PADUA score ≥8 might entail a higher risk of recurrence, and closer follow-up should be considered in these patients. [ABSTRACT FROM AUTHOR]

Purpose: To examine the mode of relapse detection and subsequent treatment after partial or radical nephrectomy in patients with low-risk (pT1, N0, Nx) kidney cancer. Methods: Retrospective study on 1404 patients treated with partial or radical nephrectomy for low-risk kidney cancer from the years 2000-2012. Scans for chest imaging (X-ray or CT) and abdominal imaging (CT, MRI, or ultrasound) are tabulated. For those patients with relapse, the site, mode of detection, and symptoms were recorded. Results: Twenty-one patients relapsed with a median follow-up of 4.1 years for patients who did not relapse. In 17 (81 %) patients, relapse was detected by imaging alone, while 4 (19 %) patients presented with symptoms. Of the patients who relapsed by imaging, 13 (76 %) were treated immediately, while 4 (24 %) continued observation. During the first 3 years of follow-up, 5762 imaging studies were performed to detect 8 relapses, with 6 patients receiving immediate treatment. The median number of imaging studies per patient per year for the first 3 years was 1.7 (interquartile range 1.0, 2.3) including 30 % CT, 3 % MRI, 36 % X-ray, and 31 % ultrasounds. Conclusion: We found a low yield of surveillance imaging in the first 3 years for pT1 kidney cancer. Nearly 1000 imaging studies were performed to detect one relapse that required treatment. Further studies are needed to evaluate the clinical impact of imaging surveillance according to recent guidelines. [ABSTRACT FROM AUTHOR]

To investigate the difference between preoperative radiologic tumor size (RTS) and postoperative pathologic tumor size (PTS) in patients who underwent nephrectomy for renal cell carcinoma. We retrospectively reviewed 257 patients who received preoperative computed tomography (CT) before radical or partial nephrectomy for renal cell carcinoma from January 2010 to May 2015 in Huashan Hospital, Shanghai. RTS was defined as the largest diameter of tumor measured by CT and PTS as the largest diameter of tumor measured in the surgical specimens. Among all subjects, mean RTS was larger than PTS (4.57 ± 2.15 vs. 4.02 ± 2.15 cm, P = 0.004) with a discrepancy of 0.55 cm. When the patients were categorized according to T stage, the mean RTS was greater than PTS in the following groups: ≤4 cm group (2.90 vs. 2.59 cm, P = 0.02), >4 and ≤7 cm group (5.08 vs. 4.38 cm, P < 0.0001), except for >7 cm (8.9 vs. 8.0 cm, P = 0.142). Among patients with clear cell RCC, the mean RTS was larger than the mean PTS (4.57 vs. 3.98 cm, P = 0.004), similar result was also seen in non-clear cell group (4.54 vs. 4.16 cm, P = 0.045). The mean RTS was larger than PTS for the approach of radical nephrectomy (RN) (5.26 vs. 4.64 cm, P = 0.01), but not for the partial nephrectomy (PN) (3.34 vs. 2.92 cm, P = 0.067). Of the 257 renal cancers, 76 tumors were down-staged when comparing radiographic and pathologic tumor maximal diameter. The proportion of down-staged tumors had no difference between different genders ( P = 0.283), different surgery approaches ( P = 0.102), and different pathology types ( P = 0.209). In this study, we found that renal tumor size was overestimated by radiography compared with pathologic results, and the T staging of some tumors was down-staged. But for patients who underwent PN, there was no difference between RTS and PTS. These results suggested that the PN should be considered first for the T1b renal tumor when tumor size was close to 4 cm, while the recommendation level of PN for T1b tumor was grade B according to EAU guidelines. [ABSTRACT FROM AUTHOR]

Background: The management of locally recurrent renal-cell carcinoma (RCC) following cryoablation remains a clinical dilemma. There is limited data regarding the management of locally recurrent disease in the setting of patients who have failed initial percutaneous cryoablation (PCA). We evaluate and report our experience with salvage PCA for local recurrence following renal cryoablation failure. Patients and Methods: We reviewed our experience with patients who underwent salvage PCA for local biopsy proven RCC recurrence following primary cryoablation procedures. Complications and oncologic outcomes were evaluated. Recurrence-free survival after primary and repeat cryoablation was plotted using the Kaplan-Meier curves. Results: A total 250 patients underwent primary cryoablation for RCC and 20 (8%) patients were identified who underwent repeat PCA for 21 locally recurrent tumors. The mean tumor size was 2.4 cm. Biopsy revealed clear cell in 14 patients, three papillary and four chromophobe RCC. All repeat cryoablation procedures were completed successfully, with no treatment failures on postprocedure imaging. There were no complications or deaths. With the median follow-up of 30 months (range 7-63), 3 (15%) patients experienced local recurrence. One patient had an enhancing lesion at 13 months following repeat PCA and underwent a third PCA. Two patients had recurrence at 6 and 35 months respectively and underwent successful laparoscopic partial nephrectomy. Local recurrence-free, metastasis-free and cancer-specific survival rates were 85%, 100%, and 100% respectively. Limitations include retrospective design and small number of patients. Conclusions: Repeat PCA after primary cryoablation failure is feasible, has a low complication rate, and acceptable short-term oncologic outcomes. Further studies with durable follow-up are required. [ABSTRACT FROM AUTHOR]

Objectives In previous experiments, we have found an increased level of class I ADH and total ADH activity in RCC tissues. Changes in cancer cells may be reflected by ADH activity in the serum and could thus be helpful for diagnostics of renal cancer. The aim of this study was to investigate a potential role of ADH and ALDH as tumor markers for RCC. Material and methods Serum samples were taken from 59 patients with RCC and 52 healthy subjects. Class III and IV of ADH and total ADH activity was measured by the photometric method. For measurement of class I and II ADH and ALDH activity, we employed the fluorometric method. Results The total activity of ADH and ADH I was significantly higher in the serum of patients with every stage of RCC compared to healthy subjects. The diagnostics criteria was higher for ADH I than for total ADH activity. The diagnostic sensitivity for ADH I was 73.36%, specificity 85.61%, predictive values of positive and negative results were 79.12 and 75.03% respectively. Area under ROC curve for ADH I was 0.748 and for total ADH 0.689. Conclusion The results suggest a potential role of ADH I as a marker for RCC. [ABSTRACT FROM AUTHOR]