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Kidney Cancer

Renal cell cancer (kidney cancer) is a disease in which malignant cells arise from tissues of the kidney. This is one of the less common types of cancer and it occurs more frequently in men compared to women. The vast majority of renal cell cancers are histologically classed as adenocarcinomas, these may be subdivided into clear cell and granular cell types (in some cases the 2 types can occur together in the same tumour). There are other less common types of non-adenocarcinoma kidney cancers including transitional cell carcinoma of the renal pelvis. Wilms' tumour is another type of kidney cancer, which is almost exclusively found in children.

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  • PubMed search for publications about Kidney Cancer - Limit search to: [Reviews]

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    MeSH term: Kidney Neoplasms
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Vachhani P, George S
VEGF inhibitors in renal cell carcinoma.
Clin Adv Hematol Oncol. 2016; 14(12):1016-1028 [PubMed] Related Publications
The arrival of targeted therapies-vascular endothelial growth factor (VEGF) pathway inhibitors and mammalian target of rapamycin (mTOR) inhibitors-and programmed death 1 (PD-1) inhibitors has transformed the management of renal cell carcinoma (RCC). Once considered fatal, with a median survival of approximately 1 year, these agents have nearly tripled overall survival and have raised hopes of a possible cure for advanced RCC. This review begins with a brief discussion of the seminal von Hippel-Lindau/hypoxia-inducible factor axis in RCC. It then discusses the pivotal trials that have investigated VEGF inhibitors in metastatic RCC, as well as in adjuvant and neoadjuvant settings. Finally, it addresses some practical considerations and future directions in the use of VEGF inhibitors in RCC.

Seo AN, Yoon G, Ro JY
Clinicopathologic and Molecular Pathology of Collecting Duct Carcinoma and Related Renal Cell Carcinomas.
Adv Anat Pathol. 2017; 24(2):65-77 [PubMed] Related Publications
Collecting duct carcinoma (CDC) and related tumors [ie, renal medullary carcinoma (RMC)] are rare types of highly aggressive renal cell carcinomas (RCC) with poor prognosis. Because of the rarity and diagnostic uncertainty of them, their molecular pathology and significance have not yet been fully elucidated. CDC, RMC, fumarate hydratase-deficient RCC (including hereditary leiomyomatosis and RCC-associated RCC HLRCC-RCC), and recently reported anaplastic lymphoma kinase (ALK)-rearrangement RCC have significant morphologic overlaps, but they are separately distinct entities having different molecular pathway and clinical settings. CDC is more likely to occur in middle to old age population with immunoreactivity for PAX8 and integrase interactor-1 proteins (INI-1). Various chromosomal and genomic alterations have been reported with inconsistent results. In contrast, RMC is more likely to occur in younger patients with sickle cell trait. In RMC, loss of INI-1 expression and OCT3/4 expression are distinguished compared with other RCCs. Finally, ALK-rearrangement RCC seems to have 2 different clinical settings, one with sickle cell trait (VCL-ALK fusion) and the other without (other fusions such as TPM3-ALK, EML4-ALK, and STRN-ALK fusions). Interestingly, VCL-ALK fusion was found in pediatric patients with sickle cell trait, whereas other fusions were detected in adolescent or adult without sickle cell trait. Taken together, CDC and related tumors such as RMC, fumarate hydratase-deficient RCC (including hereditary leiomyomatosis and RCC-associated RCC), and ALK-rearrangement RCC are the distinct entities and their recognition is important for the development of future personalized therapeutic options. This review updates the clinicopathologic features of these tumors with overlapping morphology and outcome.

Moris D, Kakavia K, Argyrou C, et al.
De Novo Renal Cell Carcinoma of Native Kidneys in Renal Transplant Recipients: A Single-center Experience.
Anticancer Res. 2017; 37(2):773-779 [PubMed] Related Publications
BACKGROUND: The risk of renal cell carcinoma (RCC) development in renal transplant recipients is 15-100 times higher than in the general population. The majority of RCCs found in renal transplant recipients develop in the recipient's native kidneys, only 9% of tumors develop in the allograft itself. The mechanisms of development of RCC in native kidneys and renal allografts are not completely understood. We present our experience in renal transplant recipients with RCC of native kidneys providing valuable and clinically applicable treatment and follow-up data.
PATIENTS AND METHODS: The records of 2,173 patients who underwent renal transplantation in our Department between March 1983 and December 2015 were retrospectively reviewed. Using these data, we analyzed the incidence and types of post-transplant RCCs, as well as their clinical courses, focusing on native malignancies.
RESULTS: We found 11 RCCs (0.5%) during the observation period in native kidneys. The mean (±SD) follow-up period was 50.54±32.80 months. Four patients died during this period (36.4%).
CONCLUSION: Most RCCs in renal transplant recipients are low-stage, low-grade tumors with a favorable prognosis. Their diagnosis is usually incidental. RCC development in the native kidney of renal transplant recipients is an early event, frequently observed within 4 to 5 years after transplantation. The different natural history of these tumors is still undefined. Further research is needed to determine whether these differences are due to particular molecular pathways or to biases in relation to the mode of diagnosis.

Mei YH, Yu JP, Li G
An extramedullary plasmacytoma in the kidney of a 14-year-old girl: Case report and review of the literature.
Medicine (Baltimore). 2017; 96(6):e6092 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Extramedullary plasmacytoma (EMP) a rare plasma cell disorder and is frequently associated with plasma cell bone marrow infiltration. Most EMPs involve mucosal lymphoid tissue, especially in the nasopharyngeal area, respiratory tract, and head and neck region. Primary involvement of the kidney is exceedingly rare.
PATIENT CONCERNS: A 14-year-old girl was admitted in our hospital with intermittent right upper quadrant pain for 1 month and recent (1 day) progressive deterioration. There was a mass found by ultrasonography in the right kidney and subsequent abdominal computed tomography scan revealed a 3 cm mass within the right kidney.
DIAGNOSES: Pathology revealed typical histology of plasmacytoma and immunohistochemistry revealed the expression of CD138, CD45, vimentin, and Kappa light chain.
INTERVENTIONS: The patient successfully underwent radical nephrectomy with an uneventful recovery. She received no chemotherapy or radiotherapy after surgery.
OUTCOMES: There was no recurrence or metastasis during a 22-month follow-up.
LESSONS: Our case study demonstrated that renal EMP with a relatively indolent clinical course, if detected at an early stage, can be treated by radical nephrectomy without adjuvant therapy. Generally, the clinical outcome and prognosis of EMP are favorable.

Luo C, Xu B, Fan Y, et al.
Preoperative Gamma-Glutamyltransferase Is Associated with Cancer-Specific Survival and Recurrence-Free Survival of Nonmetastatic Renal Cell Carcinoma with Venous Tumor Thrombus.
Biomed Res Int. 2017; 2017:3142926 [PubMed] Free Access to Full Article Related Publications
Introduction. To evaluate the prognostic significance of preoperative gamma-glutamyltransferase (GGT) on the subgroup of nonmetastatic renal cell carcinoma (RCC) with venous tumor thrombus. Materials and Methods. We retrospectively reviewed the institutional database and collected the medical data of 156 patients with nonmetastatic RCC with venous tumor thrombus between March 2004 and December 2014. Kaplan-Meier and Cox regression analyses were applied to determine the prognostic factors for cancer-specific survival (CSS) and recurrence-free survival (RFS). Results. The median value and optimal cutoff point of preoperative GGT were 23.0 and 37.5 IU/L, respectively. In the entire cohort, 67 (42.9%) patients experienced disease recurrence, and 46 (29.5%) patients died. Kaplan-Meier analysis revealed that the CSS and RFS rates were lower in patients with preoperative GGT ≥ 37.5 IU/L than in those with preoperative GGT < 37.5 IU/L. Multivariate Cox proportional hazard analysis demonstrated that high preoperative GGT was significantly associated with shorter CSS (hazard ratio [HR]: 2.115; 95% CI: 1.164-3.843; p = 0.014) and RFS (HR: 1.955; 95% CI: 1.166-3.276; p = 0.011), after adjusting other covariates. Conclusions. Preoperative GGT can serve as an independent prognostic biomarker of nonmetastatic RCC patients with venous tumor thrombus. Further prospective study is warranted to confirm our results.

Fukushi K, Hatakeyama S, Yamamoto H, et al.
Aortic calcification burden predicts deterioration of renal function after radical nephrectomy.
BMC Urol. 2017; 17(1):13 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Radical nephrectomy for renal cell carcinoma (RCC) is a risk factor for the development of chronic kidney disease (CKD), and the possibility of postoperative deterioration of renal function must be considered before surgery. We investigated the contribution of the aortic calcification index (ACI) to the prediction of deterioration of renal function in patients undergoing radical nephrectomy.
METHODS: Between January 1995 and December 2012, we performed 511 consecutive radical nephrectomies for patients with RCC. We retrospectively studied data from 109 patients who had regular postoperative follow-up of renal function for at least five years. The patients were divided into non-CKD and pre-CKD based on a preoperative estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m(2) or <60 mL/min/1.73 m(2), respectively. The ACI was quantitatively measured by abdominal computed tomography before surgery. The patients in each group were stratified between low and high ACIs. Variables such as age, sex, comorbidities, and pre- and postoperative renal function were compared between patients with a low or high ACI in each group. Renal function deterioration-free interval rates were evaluated by Kaplan-Meier analysis. Factors independently associated with deterioration of renal function were determined using multivariate analysis.
RESULTS: The median age, preoperative eGFR, and ACI in this cohort were 65 years, 68 mL/min/1.73 m(2), and 8.3%, respectively. Higher ACI (≥8.3%) was significantly associated with eGFR decline in both non-CKD and pre-CKD groups. Renal function deterioration-free interval rates were significantly lower in the ACI-high than ACI-low strata in both of the non-CKD and pre-CKD groups. Multivariate analysis showed that higher ACI was an independent risk factor for deterioration of renal function at 5 years after radical nephrectomy.
CONCLUSIONS: Aortic calcification burden is a potential predictor of deterioration of renal function after radical nephrectomy.
TRIAL REGISTRATION: This study was registered as a clinical trial: UMIN000023577.

Tian Y, Hong M, Jing S, et al.
Clinical and Prognostic Effect of Plasma Fibrinogen in Renal Cell Carcinoma: A Meta-Analysis.
Biomed Res Int. 2017; 2017:9591506 [PubMed] Free Access to Full Article Related Publications
Background. Although numerous studies have shown that plasma fibrinogen is linked to renal cell carcinoma (RCC) risk, the consistency and magnitude of the effect of plasma fibrinogen are unclear. The aim of the study was to explore the association between plasma fibrinogen and RCC prognosis. Methods. An electronic search of Embase, PubMed/MEDLINE, and the Cochrane databases was performed to identify relevant studies published prior to June 1, 2016. Results. A total of 3744 patients with RCC from 7 published studies were included in the meta-analysis. The prognostic and clinical relevance of plasma fibrinogen are evaluated in RCC patients. Statistical significance of the combined hazard ratio (HR) was detected for overall survival, cancer-specific survival, and disease-free survival. Our pooled results showed that elevated plasma fibrinogen was significantly associated with clinical stage and Fuhrman grading. The level of plasma fibrinogen was not found to be associated with tumor type and gender. Conclusions. Elevated plasma fibrinogen is a strong indicator of poorer prognosis of patients with RCC, whereas the plasma fibrinogen is not significantly associated with tumor type. Therefore, plasma fibrinogen could be used in patients with RCC for risk stratification and decision providing a proper therapeutic strategy.

Afriansyah A, Hamid AR, Mochtar CA, Umbas R
Targeted Therapy for Metastatic Renal Cell Carcinoma.
Acta Med Indones. 2016; 48(4):335-347 [PubMed] Related Publications
In the past 10 years, recent development of targeted therapy in metastatic renal cell carcinoma (mRCC) has provided a new hope and significantly enhanced the prognosis of the disease. Three class of targeted therapy were developed, including multi-targeted tyrosine kinase inhibitors (TKI), the mammalian target of rapamycin (mTOR) complex-1 kinase inhibitors, and the humanized antivascular endothelial growth factor (VEGF) monoclonal antibody. Hence, the objective of this article was to critically examine the current evidence of targeted therapy treatment for patients with mRCC. In the majority of trials evaluating targeted therapy, patients were stratified according to Memorial Sloan Kattering Cancer Center (MSKCC) risk model and the recommendation of targeted treatment based on risk features. In first-line setting (no previous treatment), sunitinib, pazopanib, or bevacizumab plus IFN-α were recommended as treatment options for patient with favorable- or intermediate- risk features and clear cell histology. Patients who progressed after previous cytokine therapy would have sorafenib or axitinib as treatment options. Clear-cell mRCC with favorable- or intermediate- risk features and failure with first-line TKI therapy might be treated with sorafenib, everolimus, temsirolimus or axitinib. However, the current evidence did not show the best treatment sequencing after first-line TKI failure. In patients with poor-risk clear-cell and non-clear cell mRCC, temsirolimus was the treatment option supported by phase III clinical trial. In addition, several new drugs, nowadays, are still being investigated and waiting for the result of phase II or III clinical trial, and this might change the standard therapy for mRCC in the future.

Kay FU, Pedrosa I
Imaging of Solid Renal Masses.
Radiol Clin North Am. 2017; 55(2):243-258 [PubMed] Related Publications
Detection of solid renal masses has increased, although it has not resulted in significant mortality reduction from renal cell carcinoma. Efforts for improved lesion characterization have been pursued and incorporated in management algorithms, in order to distinguish clinically significant tumors from favorable or benign conditions. Concurrently, imaging methods have produced evidence supporting their role as useful tools not only in lesion detection but also characterization. In addition, newer modalities, such as contrast-enhanced ultrasonography, and advanced applications of MR imaging, are being investigated. This article reviews the current role of different imaging methods in the characterization of solid renal masses.

Han JH, Yoon YE, Kim SY, et al.
Preoperative Lymphocyte-Monocyte Ratio Ameliorates the Accuracy of Differential Diagnosis in Non-Metastatic Infiltrative Renal Masses.
Yonsei Med J. 2017; 58(2):388-394 [PubMed] Free Access to Full Article Related Publications
PURPOSE: Distinguishing infiltrative renal cell carcinoma (RCC) from transitional cell carcinoma (TCC) is a challenging issue due to their radiologic similarities. We evaluated systemic inflammatory biomarkers as parameters for distinguishing tumor types.
MATERIALS AND METHODS: A computerized search of medical records from November 2005 to October 2015 identified 116 patients with infiltrative renal masses who were difficult to diagnose confirmatively in radiological study. We investigated the diagnostic efficacy among these patients with their preoperative absolute neutrophil counts (ANC), absolute lymphocyte counts (ALC), absolute monocyte counts (AMC), neutrophil-lymphocyte ratio (NLR), and lymphocyte-monocyte ratio (LMR).
RESULTS: The infiltrative RCC group demonstrated significantly lower ALC {1449/μL (1140-1896), median [interquartile range (IQR)]} than the TCC group [1860/μL (1433-2342), p=0.016]. LMR [median (IQR)] also was lower in the infiltrative RCC group [2.98 (2.32-4.14) vs. TCC group 4.10 (2.86-6.09); p=0.011]. In subgroup analysis, non-metastatic infiltrative RCC showed lower ALC and LMR and higher NLR than non-metastatic TCC. Within non-metastatic infiltrative renal masses, multivariate logistic regression analysis revealed that younger patient age and lower LMR were associated with infiltrative RCC [odds ratios (OR) 0.874, p=0.024 and OR 0.461, p=0.048, respectively]. Receiver operating characteristic curve analysis showed that younger age and lower LMR were highly predictive of non-metastatic RCC (area under the curve=0.919, p<0.001).
CONCLUSION: Age and LMR were significantly different between patients with infiltrative renal mass. These are potential markers for distinguishing between infiltrative RCC and TCC without metastasis.

López JI, Erramuzpe A, Guarch R, et al.
CD34 immunostaining enhances a distinct pattern of intratumor angiogenesis with prognostic implications in clear cell renal cell carcinoma.
APMIS. 2017; 125(2):128-133 [PubMed] Related Publications
Clear cell renal cell carcinoma is an aggressive neoplasm related to VHL gene inactivation. The molecular events derived from this initial alteration lead to a permanent intracellular pseudo-hypoxic status that stimulates vascular proliferation. The resulting increased intratumor angiogenesis is the target of most modern therapies. Although intratumor angiogenesis has received full attention in the last years, few studies have focused on its potential importance from a strict morphological approach. Intratumor angiogenesis has been analyzed in a retrospective series of clear cell renal cell carcinomas (n = 208) with long-term follow-up (n = 177). Two different patterns of angiogenesis have been highlighted with CD34 at the front of tumor invasion, termed continuous and discontinuous, respectively. The continuous pattern of angiogenesis showed a complete microvascular network surrounding totally tumor nests. Conversely, the discontinuous pattern displayed an incomplete network around tumor nests. The continuous pattern was associated to shorter 5-year (p = 0.00064, hazard ratio = 2.8) and 15-year (p = 0.014, hazard ratio = 1.7) survivals. Cox regression multivariate analysis also showed that the continuous pattern (p = 0.016373) remains a significant variable when considered together with grade (p = 0.001755) and stage (p = 0.000952). These findings support the notion that a continuous CD34(+) pattern of intratumor angiogenesis may be useful for pathologists in predicting tumor behavior in clear cell renal cell carcinomas.

Perdiki M, Datseri G, Liapis G, et al.
Anastomosing hemangioma: report of two renal cases and analysis of the literature.
Diagn Pathol. 2017; 12(1):14 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Anastomosing hemangioma (AH) is a very rare vascular tumor mimicking angiosarcoma, predominately observed in kidney and less frequently in other organs. We present two new renal cases of AH at opposite ends of the clinical presentation spectrum, provide review of the literature and compare the epidemiological, clinical and pathological profiles of renal and non-renal cases.
CASE PRESENTATION: The first occurred in a 64-year-old woman presented with back pain and the second, a multifocal lesion, in a 47-year-old man with end stage renal disease (ESRD). Histology disclosed a vascular tumor with striking anastomosing pattern, minimal nuclear atypia and locally infiltrative pattern, mimicking superficially angiosarcoma. Extramedullary hematopoiesis, extensive perirenal fat entrapment and increased number of mast cells were additional features in the second lesion. Both patients are well, without disease, 25 and 14 months after diagnosis.
CONCLUSION: Comprehensive review and analysis of the published literature show that the growing number of non-renal AHs exhibits similar epidemiologic, clinical, biologic and histologic characteristics with renal AHs and most mild differences vanish after exclusion of cases associated with ESRD. Better understanding of AH pathogenesis will contribute to optimal treatment choices.

Haider MA, Vosough A, Khalvati F, et al.
CT texture analysis: a potential tool for prediction of survival in patients with metastatic clear cell carcinoma treated with sunitinib.
Cancer Imaging. 2017; 17(1):4 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: To assess CT texture based quantitative imaging biomarkers in the prediction of progression free survival (PFS) and overall survival (OS) in patients with clear cell renal cell carcinoma undergoing treatment with Sunitinib.
METHODS: In this retrospective study, measurable lesions of 40 patients were selected based on RECIST criteria on standard contrast enhanced CT before and 2 months after treatment with Sunitinib. CT Texture analysis was performed using TexRAD research software (TexRAD Ltd, Cambridge, UK). Using a Cox regression model, correlation of texture parameters with measured time to progression and overall survival were assessed. Evaluation of combined International Metastatic Renal-Cell Carcinoma Database Consortium Model (IMDC) score with texture parameters was also performed.
RESULTS: Size normalized standard deviation (nSD) alone at baseline and follow-up after treatment was a predictor of OS (Hazard ratio (HR) = 0.01 and 0.02; 95% confidence intervals (CI): 0.00 - 0.29 and 0.00 - 0.39; p = 0.01 and 0.01). Entropy following treatment and entropy change before and after treatment were both significant predictors of OS (HR = 2.68 and 87.77; 95% CI = 1.14 - 6.29 and 1.26 - 6115.69; p = 0.02 and p = 0.04). nSD was also a predictor of PFS at baseline and follow-up (HR = 0.01 and 0.01: 95% CI: 0.00 - 0.31 and 0.001 - 0.22; p = 0.01 and p = 0.003). When nSD at baseline or at follow-up was combined with IMDC, it improved the association with OS and PFS compared to IMDC alone.
CONCLUSION: Size normalized standard deviation from CT at baseline and follow-up scans is correlated with OS and PFS in clear cell renal cell carcinoma treated with Sunitinib.

Golovastova MO, Korolev DO, Tsoy LV, et al.
Biomarkers of Renal Tumors: the Current State and Clinical Perspectives.
Curr Urol Rep. 2017; 18(1):3 [PubMed] Related Publications
Renal cell carcinoma (RCC) ranks the first death rate among the urogenital tumors, whereas its incidence follows the incidences of prostate and bladder cancer. The diagnosis of RCC at early stages allows immediately undertaking appropriate treatment, which significantly increases patients' survival rate. Early and accurate diagnosis avoids inadequate treatment, provides the disease progression forecast, and permits to apply more efficient therapy. Unfortunately, the small renal tumors are usually asymptomatic resulting in the late diagnosis and, therefore, low efficacy of treatment. Thus, sensible and preventive biomarkers are essential for early RCC detection and monitoring of its progression. So far, many attempts were performed aimed at recognizing novel informative kidney tumor biomarkers applicable for early detection of the disease and possessing prognostic and predictive capabilities. This review summarizes recent advances in renal tumor biomarkers recognition, their diagnostic and prognostic values, and clinical feasibility.

Prokopowicz G, Życzkowski M, Nowakowski K, et al.
Basic Parameters of Blood Count as Prognostic Factors for Renal Cell Carcinoma.
Biomed Res Int. 2016; 2016:8687575 [PubMed] Free Access to Full Article Related Publications
Background. Renal cell carcinoma is the most common type of kidney cancer. Taking account of morbidity and mortality increase, it is evident that searching for independent prognostic factors is needed. Aim of the Study. The aim of the study was to analyze routinely performed blood parameters as potential prognostic factors for kidney cancer. Material and Methods. We have retrospectively reviewed the records of 230 patients treated for renal cell carcinoma in the years 2000-2006. Preoperative blood parameters, postoperative histopathological results, and staging and grading were performed. To estimate the risk of tumor recurrence and cancer specific mortality (CSM) within five years of follow-up, uni- and multivariate Cox and regression analyses were used. To assess the quality of classifiers and to search for the optimal cut-off point, the ROC curve was used. Results. T stage of the tumor metastasis is the most important risk factor for early recurrence and cancer specific mortality (p < 0.001). The preoperative platelet count (PLT) above 351 × 10(3)/uL (95.3%; 55.1%) and AUC of 77% are negative prognostic factors and correlate with increased cancer specific mortality (CSM) during the five-year follow-up (p < 0.001). Increased risk of local recurrence was observed for PLT above 243.5 × 10(3)/ul (59%; 88%) and AUC of 80% (p = 0.001). The opposite was observed in the mean platelets volume (MPV) for cancer specific mortality (CSM). The cut-off point for the MPV was 10.1 fl (75.4%; 55.1%) and for the AUC is of 68.1% (p = 0.047). Conclusions. Many analyzed parameters in univariate regressions reached statistical significance and could be considered as potential prognostic factors for ccRCC. In multivariate analysis, only T stage, platelet count (PLT), and mean platelet volume (MPV) correlated with CSM or recurrent ccRCC.

Porta C, Chiellino S, Ferrari A, et al.
Pharmacotherapy for treating metastatic clear cell renal cell carcinoma.
Expert Opin Pharmacother. 2017; 18(2):205-216 [PubMed] Related Publications
INTRODUCTION: Over the past decade metastatic renal cell carcinoma (RCC) treatment landscape has dramatically evolved from the era of cytokines-based immunotherapy (which benefited very few patients, at the expenses of high toxicities) to the present era of targeted agents and novel immunotherapeutics, greatly improving the prognosis of our patients. Areas covered: Here we have reviewed the present status of the medical treatment of metastatic RCC. To do this, we interrogated the Medline database, as well as the proceedings of the main Oncological and Urological conferences for the relevant trials coducted so far. Expert opinion: Despite all the advances made in these relatively few years, further improvements are needed, since none of the available agents proved able to cure even a sigle metastatic RCC patient. In particular, advances are awaited from the results of ongoing trial of combinations of different immune checkpoint inhibitors and of immune checkpoint inhibitors with anti-VEGF/VEGFRs agents. Furthermore, a better understanding of the molecular escape pathways used by the tumor to overcome VEGFR blockade or immune activation will hopefully bring soon to the clinic more active, tailored treatments, to be used in second line and beyond.

Hongo F, Yamada Y, Ueda T, et al.
Preoperative lipiodol marking and its role on survival and complication rates of CT-guided cryoablation for small renal masses.
BMC Urol. 2017; 17(1):10 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Partial nephrectomy for small renal masses (SRM) may be useful for preserving renal function, but is technically more difficult than radical nephrectomy. Cryoablation may be performed under local anesthesia. The objective of the present study is to assess the safety and therapeutic efficacy of cryoablation with lipiodol marking for SRM.
METHODS: Cryoablation therapy was performed on 42 patients under local anesthesia. Their median age was 74 years (31-91). The median tumor diameter was 21 mm (10-42). Responses to the treatment were evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST) by contrast-enhanced CT. In six patients (14.3%) for whom it was not possible to use contrast medium, plain CT findings were assessed according to Response Evaluation Criteria in Solid Tumors (RECIST).
RESULTS: Twenty-nine (69%) and five (12%) patients achieved complete responses (CR) and partial responses (PR), respectively, while four (10%) and four (10%) patients each had stable disease (SD) and progressive disease (PD) after the first course of therapy. A second course of cryoablation therapy with lipiodol marking was performed on three out of four patients with PD after the first course of therapy, and resulted in a total of 32 patients achieving CR (76%). Four (36.4%) out of 11 patients for whom lipiodol marking was not conducted had PD, whereas none of the 31 patients for whom lipiodol marking was conducted had PD. All grade complications were reported in 11 (24.4%) patients while grade 3 in two (4.4%) patients. 11 (24.4%) A significant difference was observed in postoperative hemorrhagic events in all grades (18% in patients undergoing cryoablation without lipiodol marking vs. 0% in patients undergoing cryoablation without lipiodol marking).
CONCLUSIONS: Although further studies involving more patients are needed in order to evaluate long-term results, cryoablation therapy appears to be a useful treatment option for SRM. Preoperative marking with lipiodol was helpful for improving complication and survival rates with cryoablation.

Motoshima T, Komohara Y, Ma C, et al.
PD-L1 expression in papillary renal cell carcinoma.
BMC Urol. 2017; 17(1):8 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The immune escape or tolerance of cancer cells is considered to be closely involved in cancer progression. Programmed death-1 (PD-1) is an inhibitory receptor expressed on activating T cells, and several types of cancer cells were found to express PD-1 ligand 1 (PD-L1) and ligand 2 (PD-L2).
METHODS: In the present study, we investigated PD-L1/2 expression in papillary renal cell carcinoma (pRCC).
RESULT: We found PD-L1 expression in 29 of 102 cases, but no PD-L2 expression was seen. PD-L1 expression was not significantly correlated with any clinicopathological factor, including progression-free survival and overall survival. The frequency of PD-L1-positive cases was higher in type 2 (36%) than in type 1 (22%) pRCC; however, there was no significant difference in the percentages of score 0 cases (p value = 0.084 in Chi-square test). The frequency of high PD-L1 expression cases was higher in type 2 (23%) than in type 1 (11%), and the frequency of high PD-L1 expression cases was higher in grade 3/4 (21%) than in grade 1/2 (13%). However, no significant association was found between PD-L1 expression and all clinicopathological factors in pRCC.
CONCLUSION: High expression of PD-L1 in cancer cells was potentially associated to highly histological grade of malignancy in pRCC. The evaluation of the PD-L1 protein might still be useful for predicting the efficacy of anti-cancer immunotherapy using immuno-checkpoint inhibitors, however, not be useful for predicting the clinical prognosis.

Leone AR, Kidd LC, Diorio GJ, et al.
Bilateral benign renal oncocytomas and the role of renal biopsy: single institution review.
BMC Urol. 2017; 17(1):6 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The goal was to assess the natural history and management of patients with pathologically proven bilateral (synchronous) RO after undergoing initial partial nephrectomy (PN).
METHODS: All patients underwent either robotic/laparoscopic or open PN by two experienced genitourinary oncologists from 2005-2013. Final pathology was determined by surgical excision, CT-guided percutaneous core biopsy (CT-biopsy) or fine needle aspiration (FNA). Patient demographics, tumor characteristics (pathologic data, location, size) type of surgery, pre/post estimated glomerular filtration rate (eGFR) and surgical complications were recorded.
RESULTS: Twelve patients were identified with bilateral RO. Median age at the time of surgery was 68 years (46-77) (Table 1). The median size of the largest tumor(s) resected was 2.75 cm (1.5-5.5 cm) and second largest tumor(s) was 1.75 cm (1.0-4.0 cm). Four patients underwent bilateral staged PN and one patient underwent simultaneous bilateral PN (horseshoe kidney). Two patients underwent RFA at the time of biopsy of the contralateral mass after PN. Five patients underwent CT-bx/FNA (5/5) of the contralateral mass followed by active surveillance. Mean follow up was 34 months. There was no significant change in median creatinine pre- and post-operatively. One patient was lost to follow up and one patient died of unknown causes 5 years post-operatively. eGFR decreased an average of 16.96% post-operatively, including a single patient whose eGFR increased by 7.8% after surgery and a single patient whose eGFR did not change (Table 2).
CONCLUSIONS: Patients with bilateral renal masses and pathologically proven RO can be safely managed with active surveillance after biopsy confirmation of the contralateral mass.

Kim SH, Joung JY, Seo HK, et al.
Baseline Chronic Kidney Disease and Ischemic Method of Partial Nephrectomy Are Important Factors for the Short- and Long-Term Deterioration in Renal Function for Renal Cell Carcinoma Staged T1-T2: A Retrospective Single Center Study.
Biomed Res Int. 2016; 2016:5398381 [PubMed] Free Access to Full Article Related Publications
The renal functions of 215 patients (24 with benign renal mass, the rest with RCC staged T1-T2) who underwent partial nephrectomy (PN) between 2003 and 2014 were evaluated to identify predictors of short- and long-term deterioration in renal function after PN among renal cell carcinoma (RCC) patients with or without preoperative predisposition to chronic kidney disease (CKD) and among patients with benign renal mass. The 1- and 5-year predictive factors for de novo CKD were statistically analyzed. The incidence of de novo CKD differed significantly (p < 0.001) among patients with benign renal mass, those with RCC but no preoperative CKD predisposition, and those with RCC combined with preoperative CKD predisposition. Independent predictors for de novo CKD at 1 year postoperatively included intraoperative ischemic method, ECOG score, elevated albumin levels, male sex, and smoking exposure (in pack-years). Predictors for de novo CKD at 5 years postoperatively included hypertension, high preoperative albumin levels, De Ritis ratio (aspartate aminotransferase/alanine aminotransferase ratio), smoking exposure, and preoperative predisposition to CKD. Preoperative predisposition to CKD and ischemic method applied during PN, along with other preoperative parameters, were important factors affecting postoperative renal function deterioration in patients with T1-T2 RCC.

Dos Santos M, Brachet PE, Chevreau C, Joly F
Impact of targeted therapies in metastatic renal cell carcinoma on patient-reported outcomes: Methodology of clinical trials and clinical benefit.
Cancer Treat Rev. 2017; 53:53-60 [PubMed] Related Publications
BACKGROUND: Molecular targeted therapies have improved progression-free survival (PFS) without translating systematically into overall survival (OS) for patients with metastatic renal cell carcinoma (mRCC). In this population, patient-reported outcomes (PROs) have become a significant outcome. We evaluated the methodological quality of the assessment of PROs in randomized controlled trials (RCTs) and the clinical benefit of the different treatments including survival and quality of life (QoL).
METHODS: A systematic review identified RCTs published between January 2005 and July 2014. They were evaluated according to 11 items derived from the 2013 CONSORT PROs reporting guidelines. Survival outcomes and PROs main results were analyzed and the magnitude of clinical benefit was assessed with the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS).
RESULTS: 12 RCTs were included with a total of 22 publications. The mean CONSORT score for all items was 4.5 on an 11-point scale. No publication reported the power of the PROs analysis and only one reported a PRO hypothesis. 50% of studies did not interpret PROs in relation to clinical outcomes and only 18% discussed specific limitations of PROs and their implications for generalizability. By adding the QoL criterion to PFS, 4 trials (36.4%) obtained a high level of proven clinical benefit according to the ESMO-MCBS.
CONCLUSION: The methodology for assessing PROs in mRCC is not optimal. Efforts should focus on defining PROs endpoint and increasing the quality of reporting of QoL. New-generation therapies in mRCC should demonstrate a gain not only in survival but also in QoL to be included in the therapeutic arsenal.

Zheng G, Li H, Li J, et al.
Metastatic renal clear cell carcinoma to the rectum, lungs, ilium, and lymph nodes: A case report.
Medicine (Baltimore). 2017; 96(1):e5720 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Renal cell carcinoma metastasizing to rectum is very rare, and the unusual metastatic sites should be paid attention to during the follow-up of renal cell carcinoma.
CASE SUMMARY: We describe a case of a 65-year-old male who was diagnosed with metastatic renal cell carcinoma to rectum 10 years after the right radical nephrectomy. Histopathology and immunohistochemical examinations contribute to making differential diagnosis between rectal metastasis of renal cell carcinoma and primary rectal clear cell carcinoma. Positron emission tomography-computed tomography with fluorodeoxyglucose shows hypermetabolic activity in upper rectum and other sites of metastasis at the same time.
CONCLUSION: Possibility of unusual metastatic sites of renal cell carcinoma such as rectum indeed exists, which should not be ignored in the surveillance after resection of the primary tumor.

Ao L, Ogasahara E, Okuda Y, Hirata S
Spontaneous rupture of renal angiomyolipoma during pregnancy.
BMJ Case Rep. 2017; 2017 [PubMed] Related Publications
A renal angiomyolipoma (AML) is a rare benign tumour of kidney origin. Pregnancy is known to be associated with an increased risk of tumour rupture causing hypovolaemic shock, which is usually managed surgically or through an embolisation procedure. However, having surgery during pregnancy predisposes the mother to a preterm delivery, and the unknown influences of radiation exposure to the fetus make the management of such cases very challenging. A 30-year-old pregnant woman had a sudden onset of gross haematuria at the 20th week of her pregnancy. The MRI showed a 10 cm mass suggestive of AML in the left kidney, with evidence of an intrarenal haematoma. To avoid an iatrogenic preterm delivery and unnecessary fetal exposure to radiation, conservative management was conducted until 34 weeks of gestation, when she came to our hospital reporting of flank pain. An endovascular treatment was performed immediately after an emergency caesarean delivery.

Kuzman JA, Stenehjem DD, Merriman J, et al.
Neutrophil-lymphocyte ratio as a predictive biomarker for response to high dose interleukin-2 in patients with renal cell carcinoma.
BMC Urol. 2017; 17(1):1 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Immunotherapy with high-dose interleukin-2 (HD-IL2) results in long-term survival in some metastatic renal cell carcinoma (mRCC) patients but has significant acute toxicities. Biomarkers predicting response to therapy are needed to better select patients most likely to benefit. NLR (absolute neutrophil count (ANC)/absolute lymphocyte count (ALC)) is a prognostic and predicative biomarker in various malignancies. The goal was to determine whether NLR can predict response to HD-IL2 in this setting.
METHODS: Patients with clear cell mRCC treated with HD-IL2 were identified from an institutional database from 2003-2012. Baseline variables for the assessment of IMDC risk criteria, and neutrophil and lymphocyte count, were collected. Best response criteria were based on RECIST 1.0. Wilcoxon rank-sum test was used to evaluate the association of continuous baseline variables with disease control. NLR was stratified by ≤4 or >4. Progression free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method and Cox proportional hazard models assessed associations of NLR with survival.
RESULTS: In 71 eligible patients, median NLR in those with an objective response (n = 14, 20%) was 2.3 vs 3.4 in those without (n = 57, 80%, p = 0.02). NLR ≤4 was associated with improved progression free and overall survival. After adjustment for IMDC risk criteria, NLR remained a significant predictor of OS (ANC/ALC ≤4 vs >4, HR 0.41, 95% CI 1.09-5.46, p = 0.03; ANC/ALC continuous variable per unit change in NLR, HR 1.08, 95% CI 1.01-1.14, p = 0.03).
CONCLUSIONS: In this discovery set, NLR predicts overall survival in patients treated with HD-IL2 in mRCC, and may allow better patient selection in this setting. Data needs validation in an independent cohort.

Zhou Z, Li Y, Wang H, et al.
Biological Features of a Renal Cell Carcinoma Cell Line Derived from Spinal Metastasis.
DNA Cell Biol. 2017; 36(2):168-176 [PubMed] Related Publications
The establishment of a metastatic renal cell carcinoma (mRCC) cell line can facilitate the search for molecular mechanisms involved in RCC metastasis. A novel human mRCC cell line, designated RCC96, was established from an mRCC of the spine from a 65-year-old Chinese man. Morphology, cell cycle phase, chromosome number, cell capability of migration, tumorigenicity in nude mice, and cytogenetic features of RCC96 were investigated. Cell growth curve was detected and the cell number doubling time was 52 h. Karyotype analysis showed that these cells were polyploidy. Transmission electron microscope showed that cells were with large atypical nuclei, well-developed rough endoplasmic reticulum, rich Golgi complex, and mitochondria, as well as visible microacinar in the cytoplasm. PCR and immunofluorescence staining demonstrated that the expression of some genes such as KISS-1, MMP2, and VEGF in RCC96 was not entirely consistent with that in other RCC cell lines, indicating the differences between primary and metastatic RCC cell lines. The RCC96 cell line may serve as a useful tool for studying the molecular pathogenesis and testing new therapeutic reagents for mRCC.

Nishioka K, Fujimaki M, Kanai K, et al.
Demyelinating Peripheral Neuropathy Due to Renal Cell Carcinoma.
Intern Med. 2017; 56(1):101-104 [PubMed] Free Access to Full Article Related Publications
Renal cell carcinoma (RCC) patients who develop a paraneoplastic syndrome may present with neuromuscular disorders. We herein report the case of a 50-year-old man who suffered from progressive gait disturbance and muscle weakness. The results of a nerve conduction study fulfilled the criteria of chronic inflammatory demyelinating polyneuropathy. An abdominal CT scan detected RCC, the pathological diagnosis of which was clear cell type. After tumor resection and a single course of intravenous immunoglobulin therapy, the patient's symptoms drastically improved over the course of one year. The patient's neurological symptoms preceded the detection of cancer. A proper diagnosis and the initiation of suitable therapies resulted in a favorable outcome.

Peckova K, Martinek P, Pivovarcikova K, et al.
Cystic and necrotic papillary renal cell carcinoma: prognosis, morphology, immunohistochemical, and molecular-genetic profile of 10 cases.
Ann Diagn Pathol. 2017; 26:23-30 [PubMed] Related Publications
Conflicting data have been published on the prognostic significance of tumor necrosis in papillary renal cell carcinoma (PRCC). Although the presence of necrosis is generally considered an adverse prognostic feature in PRCC, we report a cohort of 10 morphologically distinct cystic and extensively necrotic PRCC with favorable biological behavior. Ten cases of type 1 PRCC with a uniform morphologic pattern were selected from the 19 500 renal tumors, of which 1311 were PRCCs in our registry. We focused on precise morphologic diagnosis supported by immunohistochemical and molecular-genetic analysis. Patients included 8 men and 2 women with an age range of 32-85 years (mean, 62.6 years). Tumor size ranged from 6 to 14 cm (mean, 9.4 cm). Follow-up data were available in 7 patients, ranging from 0.5 to 14 years (mean, 4 years). All tumors were spherical, cystic, and circumscribed by a thick fibrous capsule, filled with hemorrhagic/necrotic contents. Limited viable neoplastic tissue was present only as a thin rim in the inner surface of the cyst wall, consistent with type 1 PRCC. All cases were positive for AMACR, OSCAR, CAM 5.2, HIF-2, and vimentin. Chromosome 7 and 17 polysomy was found in 5 of 9 analyzable cases, 2 cases demonstrated chromosome 7 and 17 disomy, and 1 case showed only chromosome 17 polysomy. Loss of chromosome Y was found in 5 cases, including 1 case with disomic chromosomes 7 and 17. No VHL gene abnormalities were found. Papillary renal cell carcinoma type 1 can present as a large hemorrhagic/necrotic unicystic lesion with a thick fibroleiomyomatous capsule. Most cases showed a chromosomal numerical aberration pattern characteristic of PRCC. All tumors followed a nonaggressive clinical course. Large liquefactive necrosis should not necessarily be considered an adverse prognostic feature, particularly in a subset of type 1 PRCC with unilocular cysts filled with necrotic/hemorrhagic material.

Zacho HD, Nielsen JB, Dettmann K, et al.
Incidental Detection of Thyroid Metastases From Renal Cell Carcinoma Using 68Ga-PSMA PET/CT to Assess Prostate Cancer Recurrence.
Clin Nucl Med. 2017; 42(3):221-222 [PubMed] Related Publications
Ga-PSMA PET/CT is increasingly used to assess prostate cancer. Avid Ga-PSMA uptake by thyroid cancer and renal cell carcinoma (RCC) has been reported in few cases. A 75-year-old man who received a diagnosis of RCC in 2006 and prostate cancer in 2009 presented with elevated prostate-specific antigen levels (0.7 ng/mL) following prostatectomy. Ga-PSMA PET/CT showed avid Ga-PSMA uptake in 1 pelvic and 1 retroperitoneal lymph node and focal Ga-PSMA accumulation in the thyroid. Excised retroperitoneal lymph node and thyroid tissues showed metastases from RCC, whereas the pelvic lymph node exhibited metastasis from prostate cancer.

Abdelhafez M, Bastian A, Rausch S, et al.
Laparoscopic versus Open Partial Nephrectomy: Comparison of Overall and Subgroup Outcomes.
Anticancer Res. 2017; 37(1):261-265 [PubMed] Related Publications
BACKGROUND: At experienced centers, laparoscopic partial nephrectomy (LPN) can achieve similar results to those of open surgery (OPN). However, the role of LPN for complex tumors and imperative indications is under debate.
PATIENTS AND METHODS: A total of 356 cases (186 LPN and 170 OPN) between 2005-2012 were reviewed. Clinical, surgical, pathological and radiological data, including PADUA classification were analyzed.
RESULTS: In overall analysis, OPN was associated with higher tumor complexity (p≤0.03). Subgroup analysis of PADUA >8 tumors (n=85) showed no significant difference between LPN and OPN. In patients with unfavorable treatment characteristics (imperative indication/multifocal tumors, n=71) LPN was beneficial. In this subgroup, LPN led to better perioperative (p≤0.02) and postoperative (p≤0.04) outcome.
CONCLUSION: Use of LPN is associated with favorable tumor characteristics. Although no advantage was shown for LPN for tumors with higher complexity (PADUA>8), this large series confirmed the superiority of LPN for imperative indication or multifocal tumors.

Stubbs C, Bardoli AD, Afshar M, et al.
A Study of Angiogenesis Markers in Patients with Renal Cell Carcinoma Undergoing Therapy with Sunitinib.
Anticancer Res. 2017; 37(1):253-259 [PubMed] Related Publications
BACKGROUND: Sunitinib is a tyrosine kinase inhibitor (TKI) targeting tumour angiogenesis in patients with advanced renal cell carcinoma (RCC). Currently no universally agreed model exists correlating the expression of angiogenesis markers with the success of treatment.
PATIENTS AND METHODS: We retrospectively analysed archival tissue for 59 RCC patients treated with sunitinib. The expression of angiogenesis markers VEGF-A, VEGFR, PDGFββ, PDGFR, CCND1 and CA9 was assessed by immunohistochemistry (IHC) and correlated with overall survival (OS) and progression-free survival (PFS).
RESULTS: The median OS and median PFS of the whole group of patients was 24.6 months (17.3-34.2) and 19.5 months (11-27) respectively. VEGFA was positive in 29% of tumors, whereas VEGFR was expressed in only 12% of tumours. PDGFββ and its receptor were detected in a minority of cases. CCND1 and CA9 were positive in 44% and 60% of cases.
CONCLUSION: The OS and PFS achieved by our patients reflected previous observations seen with sunitinib, but no correlation was found between expression of angiogenesis markers and clinical outcome.

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