Treatment Of Kidney Cancer Research Articles

Real-life use of diagnostic biopsies before treatment of kidney cancer: results from a Norwegian population-based study

Objective: Interest in renal mass biopsies (RMBs) has increased in recent years. However, most publications are low-volume and/or single-center studies, so their generalizability is questionable. The aim of this study was to describe population-based, real-life use of diagnostic RMBs for localized and advanced kidney cancer (KC).Materials and methods: All KC patients diagnosed during 2008–2013 extracted from the database at the Cancer Registry of Norway were included. Relationships with outcome were analyzed using multivariate logistic regression and competing risks analyses.Results: Of patients treated radically for localized KC, a pretreatment RMB was used in 8.4%. For similar patients treated by observation only, the rate increased from 29.3% to 60.7% during the study period. Tumor size ≤4 cm, another malignancy, multiple tumors, old age (≥ 80 years) and second study half were independent RMB predictors. Competing risks analysis showed that among radically treated patients with localized KC, those who had undergone an RMB had a higher risk of dying of other diseases. In patients with advanced KC, biopsy was used in 54.5%, and is increasing. Study limitations include a lack of data on benign tumors, comorbidity and performance status.Conclusions: For localized KC, the use of RMBs in Norway is in line with current guidelines. Because real-world data on RMB use are scarce, this study is useful for benchmarking in future studies. Furthermore, the study shows that fewer patients with advanced KC are treated without histopathological verification, and biopsies seem to have an increasing role in tailoring treatment.

SEOM clinical guideline for treatment of kidney cancer (2017)

The goal of this article is to provide recommendations about the management of kidney cancer. Based on pathologic and molecular features, several kidney cancer variants were described. Nephron-sparing techniques are the gold standard of localized disease. After a randomized trial, sunitinib could be considered in adjuvant treatment in high-risk patients. Patients with advanced disease constitute a heterogeneous population. Prognostic classification should be considered. Both sunitinib and pazopanib are the standard options for first-line systemic therapy in advanced renal cell carcinoma. Based on the results of two randomized trials, both nivolumab and cabozantinib should be considered the standard for second and further lines of therapy. Response evaluation for present therapies is a challenge.

P113 - Long term overall survival (OS) in patients with primary metastatic kidney cancer: an analysis of 1468 patients from the Austrian National Cancer Registry (ANCR)

489Background: The introduction of thyrosinkinase inhibitors (TKI) changed the treatment of metastatic kidney cancer fundamentally. To elaborate the potential impact of TKI therapies, we studied tr...

HPLC method development and validation for the estimation of Axitinib in rabbit plasma

A rapid, sensitive, and accurate high performance liquid chromatography for the determination of axitinibe (AN) in rabbit plasma is developed using crizotinibe as an internal standard (IS). Axitinibe is a tyrosine kinase inhibitor, used in the treatment of advanced kidney cancer, which works by slowing or stopping the growth of cancer cells. The chromatographic separation was performed on a Waters 2695, Kromosil (150 mm × 4.6 mm, 5 µm) column using a mobile phase containing buffer (pH 4.6) and acetonitrile in the ratio of 65:35 v/v with a flow rate of1 mL/min. The analyte and internal standard were extracted using liquid-liquid extraction with acetonitrile. The elution was detected by photo diode array detector at 320 nm.The total chromatographic runtime is 10.0 min with a retention time for axitinibe and IS of 5.685, and 3.606 min, respectively. The method was validated over a dynamic linear range of 0.002-0.2µg/mL for axitinibe with a correlation coefficient of r2 0.999.

Calcitriol induces cell senescence of kidney cancer through JMJD3 mediated histone demethylation.

Calcitriol, also known as 1,25-dihydroxyvitamin D3 (1,25(OH)2VD3), is a biologically active form of vitamin D and has a wide range of anticancer activity against various cancer cell lines. However, the mechanism of calcitriol remains to be further studied. In this study, the biological effect and epigenetic regulation of calcitriol on kidney cancer cells were investigated. Calcitriol can significantly inhibit cell proliferation of kidney cancer cell lines 786-O (P<0.05). Calcitriol also induced cell apoptosis and senescence of 786-O and ACHN (P<0.05). Calcitriol can increase the expression of histone demethylase JMJD3 and cell senescence marker p16INK4A (P<0.05). Knockdown of JMJD3 decreased p16INK4A upregulation after calcitriol treatment (P<0.05), and also reduced calcitriol-induced cell senescence (P<0.05). This study reveals a new mechanism of anticancer activity of calcitriol by showing that histone demethylase JMJD3 induced by calcitriol increases p16INK4A expression and cell senescence. Therefore, these results provide new strategy for treatment and prevention of kidney cancer.

Multiplex Partial Nephrectomy, Repeat Partial Nephrectomy, and Salvage Partial Nephrectomy Remain the Primary Treatment in Multifocal and Hereditary Kidney Cancer

The standard of care treatment for solitary renal cell carcinoma (RCC) tumors 4 cm or less is partial nephrectomy (PNx). However, multifocal kidney cancer presents unique challenges for treating physicians. Historically, total nephrectomy and hemodialysis with possible renal transplant later was the primary therapeutic strategy for these patients. Later, as nephron sparing surgical approaches improved, PNx became the standard of care for patients presenting with multifocal and hereditary RCC. Surgeries to remove multiple renal tumors simultaneously produce different perioperative outcomes and increased risk of complications. Due to these differences in technique and outcomes, the term multiplex partial nephrectomy (MxPNx) has been coined to designate these differences. Here, we discuss the role that MxPNx continues to play in multifocal RCC.

Treatment of kidney cancer – oncological approach

Improvement in knowledge of molecular pathways of growth and developement of malignant kidney cancer has led to development of a number of efficient drugs. In this way the treatment of this condition nowadays is possible and successfull as documented by many clinical trials. New ways of treating kidney cancer tend to fulfill primary oncology goals which are to cure completely the patient or to make this serious disease a longlasting chronic disease.

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OBJECTIVES/SPECIFIC AIMS: More partial nephrectomies are performed every year as a surgical treatment for kidney cancer. However, this procedure remains technically challenging. Surgeons require a substantial number of cases before their performance plateaus. No established practice mode exists; thus, there is a need for training models to simulate real tumor excisions and kidney suturing. In this study, we seek to validate these silicone models using multiple simulations with urologists of different training levels. METHODS/STUDY POPULATION: We created silicone renal tumor models using 3D printed molds of a patient’s kidney with a mass. Medical students, urology residents, fellows, and attending surgeons are recruited to perform simulated partial nephrectomies on these models. Four trials are performed with a da Vinci surgical robot on 2 different days. We are evaluating surgeon performance and improvement using validated measures as well as operation-specific metrics. Operation-specific metrics include renal artery clamp time and surgical margins. Validated measures of self-assessed operative demand (NASA TLX) and reviewer-assessed surgical performance (GEARS) are also recorded across trials. RESULTS/ANTICIPATED RESULTS: The preliminary results of 2 medical students, 10 urology residents, 3 endourology fellows, and 2 attending urologists are reported here. Model face validity was evaluated on a 0–100 sliding scale anchored at unrealistic and realistic. Mean results thus far are 77.7 for overall feel, 82.7 for needle driving, 75.6 for cutting, and 73.2 for visual representation. Between trials 1 and 4 there was a mean reduction of 3.26 minutes in renal artery clamp time, and a 75% reduction in positive margins. There was a reduced incidence of positive surgical margins with advanced training stage. Fellows, residents, and medical students had positive tumor margins in 25%, 50%, and 75% of their trials, respectively. We expect to recruit 15 additional subjects for this study. Upon completion of data acquisition, more robust statistical comparisons and measures will be reported. DISCUSSION/SIGNIFICANCE OF IMPACT: Face validity measures indicate the model adequately represents reality. Preliminary data suggest improved surgical performance over the course of the training and better performance in urologists of higher training levels. This model may have potential for broader application and integration into minimally invasive surgery training programs.

VE14 - First report of simultaneous robotic treatment of kidney cancer and enucleation of pancreatic metastasis

VE14 - First report of simultaneous robotic treatment of kidney cancer and enucleation of pancreatic metastasis

Thérapies ablatives dans le cancer du rein : indications

Ablative therapies (AT) in kidney cancer are rising. It's important to evaluate the situation of this therapy. The aim of this study is to identify the best indications for AT treatment for kidney cancer. Review of literature using Medline and Embase databases. Study were selected based on scientific relevance. Clinical keys centered on the best requirements to indicate ablative therapies. AT is indicated according to specific tumor and patients criteria. A good initial evaluation is essential (imaging, pathology, renal function and general condition of the patient). AT gets the best results when applied to the following tumor criteria: solid tumor, length<3cm, exophytic localization, RENAL score<8. In few cases, AT could be discussed as an alternative to the reference treatment, sparing surgery: life expectancy evaluated between 3and 7years, chronic renal failure or single kidney, transplanted kidney, familial tumors. AT can be used in first line, post-surgery after local recurrence or for distant metastasis. Like every other innovative technic, indications of AT would be adjust with learning curve and cost-effectiveness. AT have to be included as a valid treatment for kidney cancer<4cm. The respect of actual indications and collection of results of AT compared to surveillance and surgery, would determinate the evolution of AT indications in the future.

Global energy and molecular interactions between Pazopanib, Axitinib and Sorafenib anticancer drugs with vascular endothelial growth factor

Pazopanib and axitinib are ATP-competitive inhibitors of the vascular endothelial growth factor receptor. They have shown to be effective and tolerable treatment options for patients with metastatic renal cell cancer and therefore have been used for the control of this disease. Sorafenib is a kinase inhibitor drug approved for the treatment of primary kidney cancer, advanced primary liver cancer, and radioactive iodine resistant advanced thyroid carcinoma. Global energy, binding sites and molecular interactions between pazopanib, sorafenib and axitinib anticancer drugs with vascular endothelial growth factor (VEGF) was probed to find the best binding energy. The structures of pazopanib, axitinib and sorafenib were drawn and constructed using window based program of Arguslab and ACDlab ChemSketch softwares. Docking studies were performed using the Patch dock and Firedock online software packages. The protein data bank (PDB) files of the crystal structure of VEGF were subjected to refinement protocols. The interactive docking method was carried out for all the conformers of each compound in the selected active site. The docked compound was assigned a score according to its fit in the ligand binding pocket (LBP) and its binding mode. The docked complexes were interpreted using Molecular Molegro viewer software. The best binding energy (minimum energy) is -19.15 Kcal/mol, -22.48 Kcal/mol and -22.37 Kcal/mol for pozapanib, sorafenib and axitinid respectively. The negative value of the binding energy shows that pozapanib, sorafenib and axitinib can selectively inhibit VEGF.

Full Modeling of High-Intensity Focused Ultrasound and Thermal Heating in the Kidney Using Realistic Patient Models.

High-intensity focused ultrasound (HIFU) therapy can be used for noninvasive treatment of kidney (renal) cancer, but the clinical outcomes have been variable. In this study, the efficacy of renal HIFU therapy was studied using nonlinear acoustic and thermal simulations in three patients. The acoustic simulations were conducted with and without refraction in order to investigate its effect on the shape, size, and pressure distribution at the focus. The values for the attenuation, sound speed, perfusion, and thermal conductivity of the kidney were varied over the reported ranges to determine the effect of variability on heating. Furthermore, the phase aberration was studied in order to quantify the underlying phase shifts using a second-order polynomial function. The ultrasound field intensity was found to drop on average 11.1dB with refraction and 6.4dB without refraction. Reflection at tissue interfaces was found to result in a loss less than 0.1dB. Focal point splitting due to refraction significantly reduced the heating efficacy. Of all the tissue parameters, perfusion was found to affect the heating the most. Small changes in temperature were seen with varying attenuation and thermal conductivity, but no visible changes were present with sound speed variations. The aberration study revealed an underlying trend in the spatial distribution of the phase shifts. The results show that the efficacy of HIFU therapy in the kidney could be improved with aberration correction. A method is proposed by which patient specific pretreatment calculations could be used to overcome the aberration and therefore make ultrasound treatment possible.

Оценка влияния различных видов ишемии в хирургическом лечении рака единственной почки на прогрессию хронической болезни почек

Мета роботи: вперше провести оцінку впливу застосування різних видів ішемії в хірургічному лікуванні раку єдиної нирки на прогресію хронічної хвороби нирок.Матеріали і методи. Проведено ретроспективний аналіз результатів лікування 68 пацієнтів, яким було виконано резекцію з приводу нирково-клітинного раку (НКР) єдиної нирки. Всі хворі проходили стаціонарне лікування у відділенні пластичної та реконструктивної урологій Національного інституту раку, урологічному відділі Львівської обласної клінічної лікарні.Результати досліджень та їх обговорення. До проведення хірургічного лікування раку нирки (РН) на 2 стадії хронічної хвороби нирок (ХХН ) був один пацієнт першої групи, один пацієнт другої групи та 6 хворих третьої групи. Відповідно 3а стадію ХХН було діагностовано у 5 хворих першої групи, 4 хворих другої групи та 19 пацієнтів третьої групи. 3b стадію ХХН діагностовано у 4 хворих першої групи, 3 хворих другої групи та 12 хворих третьої групи. З четвертою стадією ХХН, до проведення хірургічного лікування, було 3 хворих першої групи, один хворий другої групи та 7 хворих третьої групи. 5 стадію ХХН спостерігали лише у 2 хворих третьої групи. Через три місяці після проведеного хірургічного лікування прогресування ХХН спостерігали у 3пацієнтів першої групи, що становило 23, 1 %. У 2хворих другої групи, що, відповідно, складало 22, 2 %. В третій групі дослідження через три місяці після проведеного хірургічного лікування прогресування ХХН спостерігали у 5 хворих, що становило 10, 9 % випадків.

Analysis of complex postoperative treatment of kidney cancer with the use of mineral water Skhidnytsia region

The paper analyzes the results of a comprehensive rehabilitation treatment 101 patients renal carcinoma complicated with chronic renal failure. All patients were performed surgical treatment of the aforementioned disorders. The study was conducted impact assessment of complex pislyaoperatsinoho treatment of the aforementioned group of patients using mineral water Skhidnytsia region. The study found that the use of mineral water Skhidnytsia region in a comprehensive reabilitatsinomu treatment of patients who underwent surgery for cancer of the kidney, can reduce the progression of chronic kidney failure.

Possibilities of Ultrasound in Diagnosis of Kidney Cancer at the Stage of Surgery

Despite the availability of a large number of state programs for the re-equipment of state medical institutions, ultrasonic research, due to the relative simplicity of the organization of the research process and the decisiveness, still remains relevant for the examination of patients and, in particular, kidney cancer. In recent years, a number of new ultrasound techniques have emerged – three-dimensional reconstruction of ultrasound imaging, tissue harmonic technology and echocontrast with intravenous contrast agents. Due to the continuous improvement of the capabilities of ultrasound scanners and ultrasound imaging techniques, a review of the significance of ultrasound in the diagnosis and differential diagnosis of renal cell carcinoma (RCC).The purpose:to evaluate the diagnostic possibilities of ultrasound in patients with kidney tumors at the preoperative stage.Materials and methods.136 patients with kidney tumors aged 21 to 73 years were examined and treated in A.V. Vishnevsky Institute of Surgery in the period from 2012 to 2017. The study slightly dominated by men – 65.4%. All patients underwent a complex clinical and laboratory examination, which included the analysis of complaints, data of anamnesis, clinical examination, laboratory data, as well as a wide range of instrumental studies (ultrasound, MSCT and MRI). Each of the study methods was evaluated according to three criteria (localization, prevalence, presence of vein thrombosis), which are key to assessing the feasibility of surgical intervention and subsequent tactics of surgery. Evaluation of the informative value of each of the radiation methods of the study (ultrasound, MSCT, MRI) was carried out on the basis of the following criteria: sensitivity, specificity and overall accuracy of the method. All patients underwent surgical operations in various volumes, the formations were morphologically verified as RCC. As a “control” for each of the parameters used the protocol of subsequent surgery. The effectiveness of ultrasound is significantly comparable with CT and MRI in assessing such preoperative parameters as tumor localization in the kidney, the prevalence of the pathological process and thrombosis of the inferior vena cava and the main trunk of the renal vein. In the evaluation of thrombosis of segmental renal veins, ultrasound is also comparable to other methods of investigation, but these data can not be considered statistically reliable (due to the small number of observations) and their confirmation requires further study. Conclusion.In the conditions of a specialized surgical hospital focused on the diagnosis and treatment of kidney cancer, ultrasound can be comparable to CT and MRI in its effectiveness, providing the surgeon with pre-operative information sufficient for planning surgical intervention.

Cabozantinib for the treatment of kidney cancer

ABSTRACTIntroduction: Cabozantinib is a small molecule tyrosine kinase inhibitor that initially showed activity in medullary thyroid cancer and was recently approved by the Food and Drug Administration for the treatment of metastatic renal cell carcinoma after progression on first line therapy.Areas covered: In the METEOR trial, cabozantinib demonstrated significantly improved efficacy in all three endpoints; response rates, progression free survival and overall survival in a randomized trial with everolimus as an active comparator. Cabozantinib also showed activity in the front line setting in RCC within the CABOSUN trial. The study randomized untreated metastatic RCC patients to either cabozantinib or sunitinib and the former showed improved progression free survival which was the primary endpoint. The future holds promise for indications in other malignancies, given the preliminary efficacy and unique mechanism of action of cabozantinib.In this review we address the mechanism of action, pharmacodynamics and pharmacokinetics of cabozantinib, and also review the development pathway of this agent in the treatment of advanced renal cell carcinoma. The potential benefit in specific patient populations, such as poor risk patients and bone metastases subgroups is also discussed.Expert commentary: The clinical applications of cabozantinib will be addressed within the context of the current competitive therapeutic landscape of RCC.

Recent Overview of Kidney Cancer Diagnostics and Treatment

The incidence of kidney cancer has increased in the majority of countries worldwide, and this disease has relatively high lethality. For many years, the Slovak Republic has been among the countries with the highest kidney cancer incidence, in particular in 2012 (according to global estimated values) in both genders, although mainly in females. In the last few years, the Czech Republic has had the highest incidence of kidney cancer worldwide. The use of imaging techniques such as ultrasound and computerized tomography has increased the detection of asymptomatic renal cell cancer. Etiological factors include lifestyle factors such as smoking, obesity, and hypertension. Nephrectomy and partial nephrectomy are the standard treatments. Locally confined tumors in stage T1 should be treated with kidney-preserving surgery. Minimally invasive surgery is often possible as long as the surgeon has the requisite experience. For patients with metastases, overall and progression-free survival can be prolonged by pharmacotherapy with VEGF and mTOR inhibitors. The resection or irradiation of metastases can be a useful palliative treatment for patients with brain or osseal metastases that are painful or increase the risk of fracture. Minimally invasive surgery and new systemic drugs have expanded the therapeutic options for patients with renal cell carcinoma. The search for new predictive and prognostic markers is now in progress.Key words: kidney cancer - epidemiology - risk factors - pathology - diagnosis - therapy The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 2. 12. 2016Accepted: 3. 1. 2017.

Clinical outcome of patients who reduced sunitinib or pazopanib during first-line treatment for advanced kidney cancer

ObjectivesTo investigate the different outcomes in patients with metastatic renal cell carcinoma (mRCC) who receive a reduced first-line dose of sunitinib or pazopanib compared to those who continue at the standard dose. Patients and methodsAll the patients treated in 11 oncological centers in Italy for mRCC who started first-line treatment with sunitinib or pazopanib at the standard dose. Descriptive statistical tests were used to highlight differences among groups. Survival was estimated by the Kaplan-Meier method and compared across the groups using log-rank tests, the Cox proportional hazards model adjusted for statistically significant variables was also done. ResultsA total of 591 patients were included in the study. Of these, 45.7% received a reduced dose of sunitinib or pazopanib after a median treatment time of 3.6 months at the standard dose. The median overall survival in the patients who continued to receive the standard dose was 24.0 months compared to 49.4 months for those who received a reduced dose (hazard ratio = 1.80; 95% CI: 1.42–2.29; P<0.001).Only 45% of the patients received second-line therapy: 42.5% had an mTOR and 54.1% a tyrosine kinase inhibitor. Second-line overall survival was 19.8 and 11.8 months, respectively, in the patients who received, or did not, a reduced dose during first-line therapy (P = 0.007). ConclusionsToxicity-related dose reduction is a common event in mRCC patients who have started first-line therapy with either sunitinib or pazopanib. This is positively related to the outcomes of both first- and second-line therapy.

Neutrophil lymphocyte ratio (NLR) as a predictive biomarker for PD-1/PD-L1 directed therapy in metastatic non-small cell lung cancer (NSCLC).

e20633 Background: PD-1/PD-L1 directed therapy is approved in the second and first-line treatment of metastatic NSCLC. While PD-L1 expression can be predictive of outcomes with such therapy, there remains a need for additional biomarkers to guide patient (pt) selection. NLR is an easy to use biomarker that was predictive for clinical outcomes in the treatment of kidney cancer and melanoma. This study evaluated NLR as a predictor of response rate (RR), PFS and OS in metastatic NSCLC pts treated with PD-1/PD-L1 inhibitors as second line therapy. Methods: A retrospective chart review of NSCLC pts treated with PD-1/PD-L1 inhibitors was conducted. Data were collected on pt demographics, smoking status [&lt;10 pack years (PY) and ≥10 PY], histology, NLR pre-therapy and NLR post 3 doses. Correlation with RR, PFS and OS was evaluated by univariate and multivariate analyses. Results: 58 pts with NSCLC were included in the analyses. Median age was 62.5 yrs (39-85) and 34(59%) were male. 36 (62%) were Caucasian, 16(28%) African American and 6(10%) Asian. 39 (63%) had adenocarcinoma histology, 23 (40%) patients smoked &lt;10 PY and 35(60%) ≥10 PY. On Day 1, 33 (57 %) had NLR &lt;4 and 28 (48%) had NLR &lt;4 after cycle 3. 43 (74%) pts had disease control with 2 (3%) complete remissions, 22 (38%) partial responses. Pre-therapy NLR ≥4 was associated with shorter PFS (HR = 1.79 p=0.10) and shorter OS (HR =2.57; p=0.04). NLR≥4 post 3doses was associated with shorter PFS (HR= 2.14,p=0.04) and shorter OS (HR= 3.11; p=0.04). In multivariate analysis, heavy smoking (≥10 PPY) was associated with longer PFS; HR=0.50 (95% CI 0.25-1.01; p=0.05); but had no effect on OS with a HR 0.58(95%CI 0.21-1.56; p=0.28). Squamous histology appeared to have longer PFS HR=0.62 (95% CI 0.61-2.35: p =0.61), though not statistically significant. Conclusions: Pretherapy NLR ≥4 was found to be associated with shorter OS in NSCLC pts treated with PD-1/PD-L1 therapy. This suggests that NLR may be a predictive factor for benefit with PD1/PDL1 therapy. A larger sample study is warranted to validate this observation. [Table: see text]

Organ-preserving surgery for localized renal cell carcinoma: Current approaches.

e16077 Background: Introduction of modern organ-preservingapproaches in surgical treatment of kidney cancer is limited by the duration of warm ischemia used during the partial nephrectomy (PN), including surgery for elective indications. Some resection procedures require prolonged warm ischemia time resulting in acute kidney injury and development of renal failure in the postoperative period. The purpose of the study was to analyze the effectiveness of a new organ-preserving surgery method for kidney cancer. Methods: 46 patients with clinically localized renal cancer, R.E.N.A.L. score 6-10, underwent PN for elective indications. Patients were divided into two groups: the first group – 20 patients (8 patients – laparoscopic PN (LPN), 12 – open PN (OPN)) with bilateral perirenal procaine blockade (BPPB) before the resection. The second group included 26 patients (19- LPN, 7– OPN) receiving surgery without BPPB. BPPB was performed under US-control. 50 ml of 0.25% procaine solution was successively injected to the perinephric fat in upper, middle and lower kidney segments at both sides. Acute kidney injury (AKI) was diagnosed by serum creatinine level increase by 50% of the initial level and higher. Results: Patients in both groups were comparable by age – 58.35±7.5 (44–70) and 58.7±5.6 (50–65) years, and resection difficulty by R.E.N.A.L. score – 7.35±1.1 (6–10) and 7.15±1.2 (6–10), respectively. Median warm ischemia time did not differ significantly in both groups and was 20.0±2.99 (15–25) and 18.42±2.93 (15–25) min., respectively. Morphologically, all patients were diagnosed with renal cancer, surgical margins were negative. 9 (34.6%) patients of the second group developed AKI, while no AKI was registered in the first group. Urinary fistula and delayed bleeding were not observed. Conclusions: The results suppose renal protective effect of BPPB during partial nephrectomy for kidney cancer with warm ischemia time of 15-25-minutes.