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Background: We aimed to describe the effect of preoperative sarcopenia on oncologic outcomes of organ-confined renal cell carcinoma (RCC) after radical nephrectomy., Patients and Methods: A total of 632 patients with pT1-2 RCC who underwent radical nephrectomy between 2004 and 2014 were retrospectively analyzed. From preoperative computerized tomography (CT) scans, skeletal muscle index (SMI) was measured and gender-specific cutoff values at third lumbar vertebra of 52.4 cm 2 /m 2 for men and 38.5 cm 2 /m 2 for women were used to define sarcopenia. Survivals were compared and associations with sarcopenia were analyzed using Kaplan-Meier log rank tests and Cox proportional hazard regression models. Median follow-up was 83 months., Results: Of 632 patients, 268 (42.4%) were classified as sarcopenic. The sarcopenic group was more advanced in age (57 versus 53 years) and more predominantly male (71.3% versus 59.9%). Sarcopenic patients had lower body mass index (BMI, 23.0 versus 25.9 kg/m 2 ), but there was no difference in tumor size, stage, or nuclear grade. Sarcopenia was associated with poorer overall survival (OS) and cancer-specific survival (CSS; OS 94.0% versus 82.1%; p < 0.001 and CSS 97.5% versus 91.8%; p < 0.001). On multivariate analysis, sarcopenia was an independent risk factor for all-cause mortality [hazard ratio (HR) 2.58; 95% CI 1.02-6.54] and cancer-specific mortality (HR 3.07; 95% CI 1.38-6.83)., Conclusions: Sarcopenia at diagnosis was an independent risk factor for all-cause and cancer-specific mortality after radical nephrectomy for pT1-2 RCC. These findings underscore the importance of assessing presence of sarcopenia for risk stratification even among surgical candidates., (© 2021. Society of Surgical Oncology.)

A multiple receptor tyrosine kinase inhibitor, sunitinib, is a first-line therapy for clear cell renal cell carcinoma (CCRCC). Unfortunately, it has the major challenges of low initial response rate and resistance after about one year of treatment. Here we evaluated a microRNA (miRNA) and its target responsible for sunitinib resistance. Using miRNA profiling, we identified miR-96-5p upregulation in tumors from sunitinib-resistant CCRCC patients. By bioinformatic analysis, PTEN was selected as a potential target of miR-96-5p, which showed low levels in tumors from sunitinib-resistant CCRCC patients. Furthermore, PTEN and miR-96-5p levels were negatively correlated in a large The Cancer Genome Atlas kidney renal clear cell carcinoma cohort and high miR-96 and low PTEN represented poor prognosis in this cohort. Additionally, four-week sunitinib treatment increased miR-96-5p and decreased PTEN only in tumors from a sunitinib-resistant patient-derived xenograft model. We found a novel miR-96-5p binding site in the PTEN 3' UTR and confirmed direct repression by luciferase reporter assay. Furthermore, we demonstrated that repression of PTEN by miR-96-5p increased cell proliferation and migration in sunitinib-treated cell lines. These results highlight the direct suppression of PTEN by miR-96-5p and that high miR-96-5p and low PTEN are partially responsible for sunitinib resistance and poor prognosis in CCRCC., (© 2022. The Author(s).)

Purpose: To define how much of renal function was determined by the preserved renal parenchymal volume and the ischemic insult during partial nephrectomy (PN) long after surgery., Methods: We analyzed the data of 530 consecutive patients who had undergone PN. For all patients, renal function was measured preoperatively and again at 3 postoperative months, then annually using 99m Tc-diethylenetriaminepentaacetic acid renal scan. Perioperative variables potentially affecting the long-term ipsilateral glomerular filtration rate (GFR) and their time-varying contribution were assessed using a linear mixed model., Results: The mean preoperative ipsilateral GFR was 42.9 ml/min, which decreased by 27.3% at 3 months but began to recover thereafter continuing until 4 years (Δ% GFR at 1, 2, 3, 4, and 5 years: 22.3%, 18.5%, 14.7%, 10.0%, and 9.6%, respectively). Parenchymal volume reduction and ischemic time were significantly associated with postoperative ipsilateral GFR throughout observation period unvarying with time. Diabetes and proteinuria were not significant determinants of ipsilateral function at 3 months but became significant at 5 years. In multivariate analysis regarding recovery slope, volume reduction (β = -0.026, SE 0.006, P < 0.0001), preoperative ipsilateral GFR (β = -0.021, SE 0.007, P = 0.0012), proteinuria (β = -0.942, SE 0.372, P = 0.0116), and diabetes (β = -0.396, SE 0.197, P = 0.0447) were independently significant., Conclusion: Ipsilateral renal function continued to improve until 5 years after PN. Parenchymal volume loss was the major determinant and its impact on long-term ipsilateral renal function remained constant while ischemic time affected early GFR reduction with its impact diminishing over time. Patient-related factors including diabetes and proteinuria gained significance over time and became independent determinants of recovery slope., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Data regarding health behavior-related factors and systolic or diastolic blood pressure to evaluate the association between blood pressure and kidney cancer are lacking. Using nationally representative data from the Korean National Health Insurance System, 9 746 445 participants without kidney cancer between January 1, 2006 and December 31, 2009 were followed up until December 31, 2017 to obtain data regarding cancer incidence. Participants were categorized, according to blood pressure, as normal (<120/80 mm Hg), elevated (120-129/<80 mm Hg), and hypertensive (≥130/80 mm Hg) with or without antihypertensive medication, according to the 2017 American College of Cardiology and American Heart Association blood pressure guidelines. Kidney cancer was noted in 11 083 participants during the 8-year follow-up. Participants with hypertension were at higher risk for kidney cancer than those without hypertension. Participants with hypertension using medication had a higher cancer risk than those not using medication and those with elevated blood pressure. The risk of kidney cancer significantly increased with higher systolic or diastolic blood pressure, in a dose-dependent manner, even after adjusting for antihypertensive medication use. Therefore, hypertension and high systolic or diastolic blood pressure, compared with normal blood pressure, were associated with an increased risk of kidney cancer.

Objectives: To investigate whether differences in surgical details during robot-assisted partial nephrectomy impact postoperative renal function., Methods: Patient, tumor and perioperative characteristics of 751 patients who underwent robot-assisted partial nephrectomy were analyzed with respect to the difference in ipsilateral glomerular filtration rate measured by diethylenetetramine pentaacetic acid renal scan. Detailed surgical methods defined for tumor excision (cutting vs splitting), hemostasis (suturing vs clipping) and renorrhaphy (continuous vs interrupted) were analyzed for early glomerular filtration rate decline and long-term recovery., Results: The glomerular filtration rate of the entire cohort decreased by 9.8 mL/min/1.73 m 2 (22%) at 3 months postoperatively, gradually increasing thereafter. The recovery slope was 1.7 mL/min/1.73 m 2 /year during a median follow-up period of 23.0 months. Early glomerular filtration rate decline was more pronounced in the cutting group (23.5 vs 20.1%, P = 0.009). Clipping was associated with less glomerular filtration rate decline throughout the observation period, and the recovery slope was also significantly higher (2.7 vs 1.1 mL/min/1.73 m 2 /year). In multivariate analysis, early decline was associated with age, preoperative glomerular filtration rate, parenchymal volume loss and ischemia >25 min. With respect to long-term recovery, suturing had the greatest adverse impact (β = -5.060, P < 0.0001, 95% confidence interval -7.709, -2.411) in addition to parenchymal volume reduction and early decline. In the propensity-matched cohort accounting for differences in tumor size and complexity, suturing was persistently associated with a significant glomerular filtration rate decline until >2 years after surgery., Conclusions: Hemostatic sutures during robot-assisted partial nephrectomy might interfere with long-term renal function recovery irrespective of parameters that determine the initial function change. As the splitting method reduces the use of sutures, modifying these details might help preserve renal function., (© 2020 The Japanese Urological Association.)

Segmentation is fundamental to medical image analysis. Recent advances in fully convolutional networks has enabled automatic segmentation; however, high labeling efforts and difficulty in acquiring sufficient and high-quality training data is still a challenge. In this study, a cascaded 3D U-Net with active learning to increase training efficiency with exceedingly limited data and reduce labeling efforts is proposed. Abdominal computed tomography images of 50 kidneys were used for training. In stage I, 20 kidneys with renal cell carcinoma and four substructures were used for training by manually labelling ground truths. In stage II, 20 kidneys from the previous stage and 20 newly added kidneys were used with convolutional neural net (CNN)-corrected labelling for the newly added data. Similarly, in stage III, 50 kidneys were used. The Dice similarity coefficient was increased with the completion of each stage, and shows superior performance when compared with a recent segmentation network based on 3D U-Net. The labeling time for CNN-corrected segmentation was reduced by more than half compared to that in manual segmentation. Active learning was therefore concluded to be capable of reducing labeling efforts through CNN-corrected segmentation and increase training efficiency by iterative learning with limited data.

Purpose: To retrospectively evaluate the safety and efficacy of the percutaneous obliteration of urinary leakage after partial nephrectomy (PN) using coils and N-butyl-cyanoacrylate (NBCA)., Materials and Methods: Data of 10 consecutive patients who underwent percutaneous obliteration of urinary leakage after PN using coil and NBCA between February 2016 and May 2018 were retrospectively reviewed. A urinary fistulography was performed via the drainage catheter. If the fistulous tract was clearly visualized, super-selective embolization of the fistulous tract with coils and urinoma cavity sealing with NBCA was performed. In cases where the fistulous tract could not be clearly visualized, only urinoma cavity sealing was performed. Outcomes and complications were assessed by reviewing medical records and computed tomography (CT)., Results: In 7 (70%) patients who showed obvious urinary fistulous tract, coil embolization of the urinary fistulous tract, followed by sealing of the urinoma cavity with NBCA, was performed. Obliteration of the urinoma without coil embolization of the fistula tract was performed in 3 patients (30%) in whom a distinct fistulous tract could not be visualized. The median number of treatment sessions required to achieve clinical success was 1 (range, 1-5). Four patients underwent multiple repeated procedure with successful results. All patients showed gradual decrease in size or complete disappearance of urinoma on follow-up CT without evidence of urinary leakage during the follow-up period (mean, 44.6 weeks; range, 11-117 weeks). There were no procedure-related complications., Conclusions: Percutaneous obliteration of urinary leakage after PN using coils and NBCA is safe and effective., (Copyright © 2019 SIR. Published by Elsevier Inc. All rights reserved.)

Three-dimensional printing is likely to revolutionize clinical practice, and urologic surgeons could greatly benefit from early adoption of this technology. Additionally, 3-D printed kidney models have the potential to improve patients' understanding of their disease, which might ultimately result in better patient satisfaction. Overall, the use of 3-D printed models improves the efficacy of surgical procedures because they facilitate surgical planning, simplify the orientation of the target tissue, explain risk structure, and predict renal function postoperatively, thereby possibly improving surgical outcomes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: To compare the functional outcomes of open, laparoscopic, and robot-assisted partial nephrectomy (OPN, LPN, and RAPN, respectively) using diethylene triamine penta-acetic acid (DTPA)., Methods: We identified 610 patients who underwent partial nephrectomy for renal cell carcinoma (285 open partial nephrectomy [OPN], 96 laparoscopic partial nephrectomy [LPN], and 229 robot-assisted partial nephrectomy [RAPN]) with preoperative and postoperative DTPA within 1 year. We excluded multiple renal masses and history of immunotherapy or chemotherapy. Predictive factors for glomerular filtration rate (GFR) reduction were assessed using multivariate linear regression., Results: Postoperative complications and disease-free survival were similar in the three groups. Within 1 postoperative year, OPN showed a significantly lower mean ipsilateral GFR than LPN and RAPN (28.9 versus 32.4 versus 32.7 mL/min/1.73 m 2 , respectively; P < 0.001). RAPN was associated with a significantly higher total GFR than OPN within 1 year (76.6 versus 71.2 mL/min/1.73 m 2 , respectively; P = 0.001). On multivariate analysis within 1 year, operation type (OPN versus RAPN: β = 2.82; 95% confidence interval, 1.17-4.48; P = 0.001) was significantly associated with GFR reduction., Conclusion: There was no difference in postoperative complications and disease-free survival among operation types. RAPN could help to promote earlier recovery of ipsilateral GFR than OPN., (© 2019 Wiley Periodicals, Inc.)

Purpose: Classic angiomyolipoma (AML) is common benign kidney tumor. However, some studies have claimed that epithelioid angiomyolipoma (EAML) has malignant potential. We compared the patient characteristics and prognosis of EAML and classic AML to demonstrate predicting factors and poorer prognosis of EAML., Materials and Methods: The medical records of 231 patients who were diagnosed with EAML (n=27, 11.7%) or classic AML (n=204, 88.3%), were reviewed. All patients underwent computed tomography (CT) scans before operation or needle biopsy. We assessed the age, sex, tumor size, body mass index, comorbidities, and Hounsfield unit (HU) according to each CT phase. We defined the unfavorable group as patients with recurrence, metastasis and death due to tumor progression. Logistic regression analysis was used to predict EAML., Results: EAML patients were younger (41.2 years vs. 49.1 years, p=0.001), predominantly male (55.6% vs. 28.4%, p=0.005), and had a larger tumor (7.5 cm vs. 4.2 cm, p<0.001). The median pre-contrast HU was not significantly different between EAML and classic AML (29.9±23.7 vs. 14.7±41.0, p=0.071). In multivariable analysis, younger age (odds ratio [OR], 0.96; p=0.032), male sex (OR, 3.33; p=0.013), and tumor larger than 4 cm (OR, 3.8; p=0.009) were significant predictive factors. Five patients (18.5%) had unfavorable outcomes, two patients had lymph node metastasis, and three patients had lung metastasis., Conclusions: Patient and tumor characteristics can be helpful in determining the type of AML preoperatively. Younger age, male sex, and larger tumor mass may increase the possibility of diagnosing EAML. EAML has malignant potential and requires careful follow-up., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Purpose: We evaluated the changes in the incidence of benign lesions in surgically removed small renal masses (SRMs) and the effect of diagnostic tests for characterizing SRMs., Methods: We included 2,707 patients receiving surgery for SRMs (<4cm). Trends in the incidence of benign histology were evaluated according to the surgery year (period 1: 2001-2005, 2: 2006-2010, and 3: 2011-2015). Multivariable logistic regression analysis was performed to identify factors associated with benign lesions. Additionally, the number of surgeries prevented due to benign histological findings on renal mass biopsies (RMB) done on 206 patients with SRM during study period was evaluated., Results: Benign histology was identified in 192 (7.1%) patients. Incidence of benign histology was 9.7%, 7.0%, and 6.3% for period 1, 2 and 3, respectively. The uses of multiphase computed tomography and magnetic resonance imaging were more common in periods 2 and 3 than in period 1 (P<0.001). The use of RMB in period 3 was higher than in periods 1 and 2 (0.8 vs. 0.9 vs. 9.0%, P<0.001). In multivariable analysis, older age, male sex, larger tumor size, and recent surgery year (period 3 vs. 1, odds ratio = 0.62, P = 0.028) were independently associated with decreased odds of benign lesions. The number of prevented surgeries by performing RMB was 0, 10, and 39 in periods 1, 2, and 3, respectively., Conclusions: Incidence of benign histology after surgery for SRMs declined during recent years, which might be associated with the recent increased use of RMB., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: We evaluated the oncological outcomes of synchronous or metachronous brain metastasis (BM) of metastatic renal cell carcinoma (RCC) according to clinicopathologic factors., Patients and Methods: Patients with metastatic RCC (n = 93) with synchronous and metachronous BM were retrospectively identified. We analyzed patients and tumor characteristics, treatment methods, prognostic factors, BM progression, and overall survival (OS)., Results: Seventy-six patients (81.7%) received local therapy (stereotactic radiosurgery [60.2%], radiation therapy [22.6%], and neurosurgery [10.8%]), and 54 patients (58.1%) were treated with systemic medical therapy. In multivariable analysis, poor Memorial Sloan-Kettering Cancer Center (MSKCC) risk (hazard ratio [HR] 3.672; 95% confidence interval [CI], 1.441-9.36; P = .0064), sarcomatoid component (HR 4.264; 95% CI, 2.062-8.820; P = .0001), and multiple BMs (HR 2.838; 95% CI, 1.690-4.767; P = .0001) were prognostic indicators of a poorer OS outcome. Local (HR 0.436; 95% CI, 0.237-0.802; P = .0076) and systemic treatment (HR 0.322; 95% CI, 0.190-0.548; P < .0001) were independent factors for a better OS. Although OS from initial RCC diagnosis in patients with metachronous BM was better than that for patients with synchronous BM, there were no differences found between synchronous and metachronous patients in terms of BM progression and OS after the diagnosis of BM., Conclusions: Poor MSKCC risk, sarcomatoid component of histology, and multiple BMs are prognostic indicators for poor OS in patients with BM from metastatic RCC. Systemic and/or local treatment improves the OS. Because the type of BM, synchronous or metachronous, does not influence BM progression or the OS outcome, routine evaluation for BM is not recommended., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: We compared the oncological outcomes of papillary renal cell carcinoma (pRCC) with clear cell renal cell carcinoma (ccRCC) after partial nephrectomy (PN) in patients with pathologic T1a RCC., Methods: After excluding patients with synchronous multiple renal tumors, familial RCC, and pathologic stage T1b or above, 759 patients with ccRCC and 84 patients with pRCC were included. We assessed the impact of histologic subtypes on oncologic outcomes after PN in patients with pathologic T1a RCC (median follow-up duration, 67 months)., Results: There was no difference in patient and tumor characteristics between the 2 groups, except Fuhrman grade (p = 0.006). Kaplan-Meier analysis identified 5-year recurrence-free survival of 98.7 and 95.6% in patients with ccRCC and pRCC, respectively. However, 10-year recurrence-free survival in patients with ccRCC and pRCC was 96.1 and 73.0%, respectively (p < 0.001). Recurrence ≥5 years post surgery was more common in patients with pRCC compared with those with ccRCC (0.3 vs. 4.8%; p < 0.001). In multivariate analysis, pRCC [hazard ratio (HR) 5.309; p = 0.001] was a significant risk factor for recurrence after PN in patients with pathologic T1a RCC, in addition to larger tumor size (HR 1.861; p = 0.038) and Fuhrman grade ≥3 (HR 5.176; p = 0.003)., Conclusions: In patients with pathologic T1a RCC, recurrence after PN occurred more commonly in pRCC compared with ccRCC. As over half of the recurrence cases in patients with pRCC occurred ≥5 years post surgery, a longer follow-up time is required, even for those with pathologic stage T1a disease.

Purpose: Recently, several studies have shown that the De Ritis ratio (aspartate transaminase/alanine transaminase) can be a useful prognostic biomarker for certain types of malignant tumors. However, the prognostic value of the De Ritis ratio in patients with upper tract urothelial carcinoma remains largely unknown. The aim of the present study was to evaluate the prognostic significance of the De Ritis ratio in patients who had undergone radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma., Methods: In total, 1049 patients who underwent RNU at eight institutions from 2004 to 2015 were reviewed retrospectively. The De Ritis ratio and conventional clinicopathological parameters were analyzed. Survival analysis was performed using the Kaplan-Meier method and log-rank test. Multivariate analysis was carried out using the Cox proportional hazards regression model. De Ritis ratio cutoff values were derived from receiver operating characteristic (ROC) curves., Results: ROC analysis showed the cutoff De Ritis ratio for overall death to be 1.6 (p = 0.002). The cancer-specific survival (CSS) and overall survival (OS) were significantly shorter for patients with a high De Ritis ratio (>1.6). Multivariate analysis revealed an independent relationship between an increased De Ritis ratio (>1.6) and shorter CSS (hazard ratio, HR 2.49, 95% confidence interval, CI 1.70-3.64; p = 0.001) and OS (HR 1.84, 95% CI 1.34-2.52; p = 0.001)., Conclusion: The De Ritis ratio can be a significant predictor of oncological outcomes in patients with upper urinary tract urothelial carcinoma after surgery.

Introduction: We aimed to evaluate the impact of preoperative ureteral catheter insertion on urinary leakage after partial nephrectomy (PN) in patients with renal cell carcinoma., Methods: We reviewed the data of 893 patients with renal cell carcinoma who underwent PN and divided them according to ureteral catheter placement. The impact of ureteral catheter placement on postoperative urinary leakage was evaluated by using multivariate analysis., Results: Ureteral catheters were inserted in 397 (44.5%) patients. Patients with ureteral catheter insertion had larger tumors (2.4 vs. 2.6 cm; P = .031); however, the RENAL nephrometry scores were comparable (P = .131). Robotic PN was more common in patients with ureteral catheters (11.1 vs. 53.9%; P < .001). Urinary leakage did not differ according to ureteral catheter placement (3.4 vs. 3.5%; P = .936). Although tumor size (P = .002), ureteral catheter insertion (P < .001), and operative methods (P < .001) were significantly different according to surgeons, the rate of urinary leakage was similar (surgeon A: 4.0%, surgeon B: 4.6%, surgeon C: 1.5%, others: 2.9%; P = .294). In multivariate analysis of preoperative variables, age and RENAL nephrometry scores were associated with urinary leakage. In multivariate analysis of preoperative and intraoperative variables, the operative method, collecting system status, and intraoperative transfusion, but not ureteral catheter insertion, were related to urinary leakage., Conclusions: Ureteral catheter insertion does not appear to reduce the risk of urinary leakage after PN, and visibility during PN with meticulous bleeding control is important in preventing urinary leakage after PN., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Partial nephrectomy aims to maintain renal function by nephron sparing; however, functional changes in the contralateral kidney remain unknown. We evaluate the functional change in the contralateral kidney using a diethylene triamine penta-acetic acid (DTPA) renal scan and determine factors predicting contralateral kidney function after partial nephrectomy. A total of 699 patients underwent partial nephrectomy, with a DTPA scan before and after surgery to assess the separate function of each kidney. Patients were divided into three groups according to initial contralateral glomerular filtration rate (GFR; group 1 : <30 ml·min -1 ·1.73 m -2 , group 2 : 30-45 ml·min -1 ·1.73 m -2 , and group 3 : ≥45 ml·min -1 ·1.73 m -2 ). Multiple-regression analysis was used to identify the factors associated with increased GFR of the contralateral kidney over a 4-yr postoperative period. Patients in group 1 had a higher mean age and hypertension history, worse American Society of Anesthesiologists score, and larger tumor size than in the other two groups. The ipsilateral GFR changes at 4 yr after partial nephrectomy were -18.9, -3.6, and 3.9% in groups 1 , 2 , and 3 , respectively, whereas the contralateral GFR changes were 10.8, 25.7, and 38.8%. Age [β: -0.105, 95% confidence interval (CI): -0.213; -0.011, P < 0.05] and preoperative contralateral GFR (β: -0.256, 95% CI: -0.332; -0.050, P < 0.01) were significant predictive factors for increased GFR of the contralateral kidney after 4 yr. The contralateral kidney compensated for the functional loss of the ipsilateral kidney. The increase of GFR in contralateral kidney is more prominent in younger patients with decreased contralateral renal function., (Copyright © 2017 the American Physiological Society.)

Purpose: Pulmonary embolism with viable tumor cells developed after surgery for renal cell carcinoma may metastasize to lung. We investigated the incidence and fate of newly developed pulmonary embolism after surgery for renal cell carcinoma with vena cava thrombus., Methods: Among 4549 renal cell carcinoma patients treated with curative surgery at our institute from 1998 to 2015, 81 non-metastatic renal cell carcinoma patients with vena cava thrombus were included. The clinical course of pulmonary embolism and its impact on oncological outcomes were assessed., Results: Postoperatively, pulmonary embolism developed in 13 patients (16.0%), who had higher level of vena cava thrombus (p = 0.004), more frequent liver mobilization (p = 0.005), and higher amount of intraoperative transfusion (p = 0.024) than patients without pulmonary embolism. The rate of lung metastasis was similar between patients with and without pulmonary embolism (30.8 vs. 35.3%, p = 1.000). In the multivariate analysis, the significant risk factors for disease recurrence were non-clear cell histology (p = 0.014) and larger primary renal tumor size (p = 0.032). Non-clear cell histology (p = 0.003) was the only significant risk factor for cancer-specific survival. Pulmonary embolism was not associated with both recurrence-free and cancer-specific survival., Conclusions: Pulmonary embolism after surgery for renal cell carcinoma with vena cava thrombus was not associated with worse oncological outcomes and can be closely followed up with anticoagulation therapy.

Purpose: To evaluate the impact of tumor location on local recurrence in upper tract urothelial carcinoma (UTUC)., Patients and Methods: Among UTUC patients who underwent radical nephroureterectomy, 192 with renal pelvic tumors and 161 with ureteral tumors were included. Local recurrence was divided into regional lymph node recurrence (rLNR) and surgical bed recurrence (SBR)., Results: During a mean follow-up of 73 months, local recurrence occurred in 33 patients (9.3%). The postoperative 5-year local recurrence-free survival (80.5% vs. 94.2%; P = .002), rLNR-free survival (89.8% vs. 96.5%; P = .046), and SBR-free survival (88.3% vs. 97.6%; P = .005) were poorer in ureteral tumor than renal pelvic tumor. Ureteral tumor (hazard ratio [HR], 2.552; P = .017), high-grade tumor (HR, 3.064; P = .016), and advanced tumor stage (T3 or greater) (HR, 3.236; P = .002) were associated with local recurrence. Ureteral tumor (HR, 3.516; P = .033) and advanced tumor stage (HR, 2.907; P = .039) were risk factors for SBR. Although tumor location was not associated with rLNR, lymphovascular invasion (HR, 5.451; P < .001) and high-grade tumor (HR, 4.191; P = .012) were related to rLNR., Conclusion: Ureteral tumors are associated with local recurrence in the form of SBR. Adjuvant radiotherapy or surgical techniques aimed at reducing the risk of SBR should be considered in patients with ureteral tumors., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the validity of hand-assisted laparoscopic partial nephrectomy (HALPN) for small renal masses, patients who underwent HALPN, robot-assisted laparoscopic partial nephrectomy (RALPN), or open partial nephrectomy (OPN) at a single medical institution were compared in terms of perioperative outcomes., Patients and Methods: In this retrospective cohort study, all 590 consecutive patients who underwent HALPN (n=89), RALPN (n=147), or OPN (n=354) between July 2011 and April 2014 in a single institute were compared in terms of perioperative outcomes, including the mean operative time, warm ischemia time (WIT), length of the hospital stay, change in the estimated glomerulofiltration rate (eGFR), duration of analgesic use, surgical margins, and adverse events. The patient groups were compared by a multivariate regression model, in which adjustments were made for differences in baseline demographic and tumor characteristics., Results: OPN associated with a significantly longer mean operative time (187 minutes) than RALPN (162 minutes; p<0.001) or HALPN (172 minutes; p=0.013), a longer hospital stay (7.3, 5.3, and 5.9 days, respectively; p<0.001 and <0.001, respectively), and a longer duration of analgesic use (6.6, 4.6, and 5.4 days, respectively; p<0.001 and <0.001, respectively). HALPN and RALPN were equivalent in terms of operative time. RALPN had a significantly longer WIT than HALPN and OPN (p<0.001 and <0.001, respectively). HALPN had a significantly longer hospital stay than RALPN (p=0.026). The three methods differed in terms of eGFR change (p=0.028), but multivariate analysis found that the surgical method was not a significant factor for eGFR. The three methods did not differ in terms of complication rates., Conclusions: HALPN associated with shorter operative and convalescence times compared with OPN. HALPN was generally not inferior to RALPN in terms of perioperative outcomes, although it associated with a longer convalescence.

Purpose: This study aimed to investigate the effects of lymph node dissection (LND) on upper tract urothelial carcinoma (UTUC) without suspicious lymph node (LN) metastasis on preoperative imaging studies., Methods: From 1998 to 2012, 418 UTUC patients without suspicious LN metastasis on preoperative imaging studies were included. Patients were divided into two groups according to the performance of LND. The effects of LND on oncological outcomes were assessed after adjusting other variables. The mean follow-up duration was 69 months., Results: Among the 132 patients who underwent LND, LN metastasis was pathologically identified in 16 patients (12.1 %). The median number of resected LNs for patients who underwent LND was 7. On multivariate analysis, the number of resected LNs and pathologic T stage was significant predictors of LN metastasis. The 5-year recurrence-free survival was 76.4 % for patients without LND and 65.4 % for patients with LND (p = 0.126). In addition, there was no difference in 5-year overall survival between the 2 groups (without LND; 71.7 % vs. with LND; 72.1 %, p = 0.756). Multivariate analysis showed that pathologic T stage, tumor grade, and lymphovascular invasion were risk factors for recurrence. Age at surgery, tumor size, pathologic T stage, tumor grade, and lymphovascular invasion were significantly associated with overall survival. However, performance of LND was not associated with recurrence and survival., Conclusions: LND could be selectively performed in patients with clinically LN-negative UTUC based on patient/tumor characteristics and operative findings although sufficient LNs should be removed if LND is to be performed.

Introduction: To investigate whether ureteroscopic biopsy (URS-Bx) for upper tract urothelial carcinoma (UTUC) before radical nephroureterectomy affects intravesical recurrence (IVR)., Patients and Methods: Of the 515 patients receiving radical nephroureterectomy for UTUC between 1998 and 2012, 387 patients were included for the analysis. URS-Bx was performed in 69 patients (17.8%). Patients were stratified according to tumor location, and the impact of URS-Bx on IVR was evaluated after adjusting for other clinicopathologic variables., Results: IVR occurred in 163 patients (42.1%). The postoperative 5-year IVR-free survival was not significantly different according to URS-Bx in the overall patient group (54.0% vs 39.3%, p = 0.056). In patients with renal pelvic tumor, IVR-free probability was lower in patients with URS-Bx than in patients without URS-Bx (39.6% vs 62.2%, p = 0.012), although IVR-free survival in patients with ureteral tumor was equivalent (36.7% vs 45.8%, p = 0.946). In multivariate analysis, previous bladder tumors (hazard ratio [HR], 1.65; p = 0.016) were a significant risk factor for IVR in all patients and ureteral tumor location (HR, 1.35; p = 0.071) was associated with IVR, although statistical significance was not achieved. In patients with renal pelvic tumor, URS-Bx HR, 1.98; p = 0.020 was the only risk factor for IVR. However, URS-Bx was not associated with IVR in patients with ureteral tumor, although previous bladder tumor HR, 1.74; p = 0.028 was a risk factor for IVR., Conclusion: URS-Bx is a significant risk factor for IVR in patients with renal pelvic tumor and should be performed after sufficient consideration in these patients if other examinations are uncertain.

The prognostic value of the expression of vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2), platelet-derived growth factor (PDGF)-β, and PDGF receptor (PDGFR)-β in papillary renal cell carcinoma (pRCC) is unknown. A total of 145 patients, who were confirmed to have pRCC, were analyzed. Expression levels of molecular markers were assessed via immunohistochemistry. The median follow-up period for all patients was 52.0 (interquartile range, 34.5-90.5) months. Among the cohort of 145 patients, high VEGF expression was observed in 100 (69.0%) patients, whereas high expression of VEGFR2, PDGF-β, and PDGFR-β was observed in 64 (44.1%), 42 (29.0%), and 30 (20.7%) patients, respectively. Only patients with high VEGFR2 expression exhibited improved 10-year recurrence-free survival (85.3% versus 58.1%; P=.005) and cancer-specific survival (86.4% versus 70.1%; P=.014) rates compared with individuals who exhibited low expression. Multivariate analysis revealed that high VEGFR2 expression was an independent prognostic factor for recurrence (hazard ratio, 0.326; P=.006) and cancer-specific mortality (hazard ratio, 0.334; P=.046). During follow-up, 17 patients received targeted drug therapy. Patients with high VEGFR2 expression showed a better initial response (partial response, 40%; stable disease, 20%; progressive disease, 40%) than patients with low expression did (partial response, 0%; stable disease, 58.3%; progressive disease, 41.7%; P=.052). pRCC with high VEGFR2 expression seems to be associated with a better initial response to targeted drug therapy and a better prognostic outcome., (Copyright © 2016 Elsevier Inc. All rights reserved.)

This study aimed to determine patients with T1b renal cell carcinoma (RCC) who could benefit from partial nephrectomy (PN) and method to identify them preoperatively using nephrometry score (NS). From a total of 483 radical nephrectomy (RN)-treated patients and 40 PN-treated patients who received treatment for T1b RCC between 1995 and 2010, 120 patients identified through 1:2 propensity-score matching were included for analysis. Probability of chronic kidney disease (CKD) until postoperative 5-years was calculated and regressed with respect to the surgical method and NS. Median follow-up was 106 months. CKD-probability at 5-years was 40.7% and 13.5% after radical and PN, respectively (P = 0.005). While PN was associated with lower risk of CKD regardless of age, comorbidity, preoperative estimated renal function, the effect was observed only among patients with NS ≤ 8 (P < 0.001) but not in patients with NS ≥ 9 (P = 0.746). Percent operated-kidney volume reduction and ischemia time were similar between the patients with NS ≥ 9 and ≤ 8. In the stratified Cox regression accounting for the interaction observed between the surgical method and the NS, PN reduced CKD-risk only in patients with NS ≤ 8 (hazard ratio [HR], 0.054; P = 0.005) but not in ≥ 9 (HR, 0.996; P = 0.994). In T1b RCC with NS ≥ 9, the risk of postoperative CKD was not reduced following PN compared to RN. Considering the potential complications of PN, minimally invasive RN could be considered with priority in this subgroup of patients., Competing Interests: The authors have no potential conflicts of interest to disclose.

We aimed to identify prognostic factors associated with progression-free survival (PFS) and overall survival (OS) in metastatic renal cell carcinoma (mRCC) patients treated with sorafenib. We investigated 177 patients, including 116 who received sorafenib as first-line therapy, using the Cox regression model. During a median follow-up period of 19.2 months, the PFS and OS were 6.4 and 32.6 months among all patients and 7.4 months and undetermined for first-line sorafenib-treated patients, respectively. Clinical T3-4 stage (hazard ratio [HR] 2.56) and a primary tumor size >7 cm (HR 0.34) were significant prognostic factors for PFS among all patients, as were tumor size >7 cm (HR 0.12), collecting system invasion (HR 5.67), and tumor necrosis (HR 4.11) for OS ( p < 0.05). In first-line sorafenib-treated patients, ≥4 metastatic lesions (HR 28.57), clinical T3-4 stage (HR 4.34), collecting system invasion (univariate analysis HR 2.11; multivariate analysis HR 0.07), lymphovascular invasion (HR 13.35), and tumor necrosis (HR 6.69) were significant prognosticators of PFS, as were bone metastasis (HR 5.49) and clinical T3-4 stages (HR 4.1) for OS ( p < 0.05). Our study thus identified a number of primary tumor-related characteristics as important prognostic factors in sorafenib-treated mRCC patients., Competing Interests: The authors would like to disclose the following: Choung-Soo Kim was a consultant for Pfizer, Bristol-Myers Squibb, and Taiho and received advisory and/or speaker fees from these companies. Jinsoo Chung was a consultant for Pfizer and Novartis and received advisory and/or speaker fees from Pfizer, Novartis, and Bayer. However, the authors declare that there is no conflict of interests regarding the publication of this paper.

Purpose: We evaluated the value of metastasectomy in patients treated with targeted therapy for metastatic renal cell carcinoma (mRCC)., Methods: The medical records of 325 patients who presented with mRCC were reviewed; among these patients, 33 underwent complete metastasectomy followed by targeted therapy (complete metastasectomy group), 29 underwent incomplete metastasectomy followed by targeted therapy (incomplete metastasectomy group), and 263 treated with targeted therapy alone (non-metastasectomy group). We estimated progression-free and overall survivals using Kaplan-Meier curves. A Cox proportional hazards regression model was used to estimate the prognostic significance of metastasectomy., Results: Clinicopathological variables did not differ among the three groups except for age, history of nephrectomy, type of metastasis, the International Metastatic Renal Cell Carcinoma Database Consortium risk groups, histology, and bone metastasis. The median progression-free survivals were 29.5, 18.8, and 14.8 months in the complete, incomplete, and non-metastasectomy groups (p < 0.001). Complete metastasectomy (hazard ratio 0.431, p = 0.001) was an independent predictor of disease progression, along with targeted agents, risk groups, sarcomatoid feature, and number of metastatic sites. The median overall survivals were 92.5, 29.6, and 23.5 months in the complete, incomplete, and non-metastasectomy groups (p < 0.001). Complete metastasectomy (hazard ratio 0.378, p = 0.001) was an independent predictor of overall survival, along with targeted agents, type of metastasis, risk groups, sarcomatoid feature, and number of metastatic sites., Conclusions: Complete metastasectomy performed before targeted therapy might improve progression-free and overall survivals in patients with mRCC.

Purpose: This study was designed to evaluate and compare the oncological outcomes of patients with pathological T1a (pT1a) small renal cell carcinomas (RCCs) with those with incidental pathological T3a (pT3a) RCCs who have been treated using partial nephrectomy (PN)., Methods: We retrospectively evaluated the records of 1367 consecutive patients who underwent PN for small RCCs (≤4 cm) between 1997 and 2014. The curves for recurrence-free, cancer-specific, and overall survival were estimated using the Kaplan-Meier method. Cox regression analysis was used to estimate the prognostic significance of each variable., Results: Of the 1367 small RCC patients identified, 1324 (96.8 %) had pT1a lesions and 43 (3.2 %) had pT3a lesions. The median ages of the pT1a and pT3a patients were 53.9 and 58.1 years, respectively. Patients received follow-up for a median of 54 months. The 5- and 10-year RFS rates in patients with pT1a and pT3a RCCs were 98.0 and 95.2 %, and 94.4 and 95.2 %, respectively (P = 0.521). None of the patients with recurrent tumors in the pT3a group have died by the time of the writing of this report. A multivariate Cox proportional hazards model showed that tumor size was a significant predictor of RFS and CSS (P < 0.05). However, pT stage (pT3a vs. pT1a) was not a significant predictor of RFS, CSS, or OS (P = 0.104, P = 0.573, and P = 0.441, respectively)., Conclusions: Our study found that pT3a stage disease following PN for small RCCs (≤4 cm) had similar oncological outcomes to those of pT1a stage.

Purpose: To compare renal functional outcomes in patients with a small renal mass undergoing robot-assisted partial nephrectomy using warm ischemia (wRAPN) or open partial nephrectomy using cold ischemia (cOPN)., Methods: This study included 185 patients who underwent partial nephrectomy and were assessed by preoperative and postoperative diethylene triamine penta-acetic acid renal scintigraphy. Variables associated with postoperative operated-side glomerular filtration rate decrement (ΔGFR) were assessed using multivariate analysis. Exact 1:1 propensity score matching was performed using variables related to ΔGFR. Furthermore, 30 patients who underwent wRAPN were matched with 30 patients who underwent cOPN, and their differences in ΔGFR were calculated., Results: Patients who underwent cOPN were older (p = 0.025) and had shorter ischemia time (p < 0.001) than patients who underwent wRAPN. Multivariate analysis showed that surgical method, preoperative operated-side GFR and RENAL nephrometry score were significantly associated with operated-side ΔGFR. After propensity score matching, postoperative 3-month (14.8 vs. 7.3 mL/min/1.73 m(2), p = 0.057) and 1-year operated-side ΔGFR (11.4 vs. 2.8 mL/min/1.73 m(2), p = 0.031) was higher after wRAPN than after cOPN in patients with ischemia time ≥25 min, but did not differ in patients with ischemia time <25 min. Within the matched pairs, cOPN resulted in lower operated-side ΔGFR than wRAPN in patients with ischemia time ≥25 min (-6.9 mL/min/1.73 m(2), p = 0.047). Moreover, total GFR decrement was slightly lower with cOPN than with wRAPN (-7.2 mL/min/1.73 m(2), p = 0.086)., Conclusions: cOPN was superior to wRAPN in patients with a small renal mass and ischemia time ≥25 min. However, wRAPN yielded renal functional outcomes comparable to those of cOPN when ischemia time was <25 min.

Purpose: We report the diagnostic accuracy of renal mass biopsy for a small renal mass (4 cm or less) and identify predictors of successful renal mass biopsy in a contemporary cohort of patients from 2 large tertiary referral centers., Materials and Methods: A total of 442 biopsies of renal tumors 4 cm or less at 2 tertiary centers between 2008 and 2015 were included in study. Biopsy outcomes (malignant, benign or nondiagnostic) and concordance rates between renal mass biopsy and final surgical pathology were determined. Univariate and multivariate logistic regression analyses were performed to identify factors indicative of nondiagnostic biopsy., Results: The initial biopsy was diagnostic in 393 cases (88.9%) and nondiagnostic in 49 (11.1%). Of diagnostic biopsies 76% revealed renal cell carcinoma and 24% were benign. Renal cell carcinoma histological subtyping and grading was possible in 90.2% and 31.3% of cases, respectively. A second biopsy was performed in 11 of the 49 nondiagnostic cases and a diagnosis was possible in 100%, including renal cell carcinoma in 10 and oncocytoma in 1. Small tumor size, cystic nature of tumors and biopsy during the initial years of the study were independent predictors of nondiagnostic biopsy. The rates of accuracy in identifying malignancies, histiotyping and 2-tier grading between renal mass biopsy and surgical pathology were 97.1%, 95.1% and 68.8%, respectively., Conclusions: Renal mass biopsy for a small renal mass can be performed accurately. Nondiagnostic renal mass biopsy was common for smaller masses and cystic masses, and during the initial years of the study. A second biopsy should be considered in nondiagnostic biopsy cases., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to retrospectively assess whether measurement of quantitative enhancement during three-phase MDCT can help differentiate clear cell renal cell carcinoma (RCC) from papillary RCC, chromophobe RCC, and fat-poor angiomyolipoma., Materials and Methods: During preoperative three-phase MDCT (unenhanced, corticomedullary, and early excretory phases), 563 lesions were identified in 552 consecutively registered patients. The lesions were assessed for attenuation in each phase, and the attenuation values were compared by t test. Cutoff analysis of enhancement values (percentage enhancement ratio, enhancement change, and absolute washout ratio) was performed to determine optimal thresholds for the four types of lesions., Results: The mean attenuation of clear cell RCC was significantly greater than that of papillary RCC and chromophobe RCC in the corticomedullary phase (clear cell, 139.7 HU; papillary, 56.8 HU [p = 0.003]; chromophobe, 85.4 HU [p = 0.005]) and early excretory phase (clear cell, 86.9 HU; papillary, 73.4 HU [p = 0.03]; chromophobe, 68.2 HU [p = 0.02]). It was also significantly greater than that of fat-poor angiomyolipoma in the corticomedullary phase (139.7 vs 99.6 HU, p = 0.02). Establishment of threshold enhancement values helped to differentiate clear cell RCC from papillary RCC, chromophobe RCC, and fat-poor angiomyolipoma with the following accuracies: percentage enhancement ratio, 84.7% (399/471) for papillary RCC, 71.1% (325/457) for chromophobe RCC, and 81.9% (377/460) for fat-poor angiomyolipoma; enhancement change, 80.9% (381/471) for papillary RCC, 70.2% (321/457) for chromophobe RCC, and 80.6% (371/460) for fat-poor angiomyolipoma; absolute washout ratio, 88.5% (417/471) for papillary RCC, 74.1% (339/457) for chromophobe RCC, and 85.0% (391/460) for fat-poor angiomyolipoma., Conclusion: Quantitative enhancement measurement may be useful for differentiating clear cell RCC from papillary RCC, chromophobe RCC, and fat-poor angiomyolipoma.

Purpose: We investigated the expression status of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF)-B and their receptors in organ-confined clear cell renal cell carcinoma (ccRCC) to evaluate their prognostic significance after radical surgery., Methods: In 758 consecutive patients diagnosed with pT1-2N0 ccRCC between 2007 and 2012, we prospectively investigated the expression levels of VEGF, PDGF-B, VEGF receptor (VEGFR) and PDGF receptor (PDGFR)-β via immunohistochemistry. Clinicopathologic parameters and expression of the angiogenic factors were analyzed with respect to recurrence-free survival (RFS) after nephrectomy. The median follow-up was 29.5 months (IQR 21.5, 39.6) after surgery., Results: Partial nephrectomy had been performed in 48.5 % of the patients, and tumors were staged as pT1a in 514 (67.8 %), pT1b in 192 (25.3 %) and pT2 in 52 (6.9 %). VEGF, PDGF and their receptors were identified in the cytoplasm and membranes of the tumor cells. Expression level of VEGFR inversely correlated with both tumor size (r = -0.076, p = 0.014) and nuclear grade (r = -0.297, p = 0.004). As for PDGF-B, the expression level showed an inverse correlation with tumor size (r = -0.216, p < 0.001) while PDGFR-β inversely correlated with nuclear grade (r = -0.341, p = 0.001). On multivariate analysis, age, pathologic stage, nuclear grade and PDGFR-β expression (high vs. low or none, HR 3.121 95 % CI 1.300-7.493, p = 0.011) were independently prognostic of RFS after nephrectomy., Conclusions: In organ-confined ccRCC, high expression of PDGFR-β was independently predictive of poorer RFS after nephrectomy.

Purpose: The aim of this study was to evaluate the effect of renal tumor anatomical characteristics on renal function change after partial nephrectomy using the scoring systems and the glomerular filtration rate (GFR) estimated from diethylene triamine penta-acetic acid (DTPA) scans., Methods: Patients who underwent DTPA renal scans before and after partial nephrectomy from January 2009 to December 2011 were identified retrospectively. The anatomical characteristics of renal tumors were standardized using the RENAL, PADUA and C-index scoring systems. Associations between scoring systems and change in GFRs were evaluated using a correlation coefficient. Predictors of GFR change and postoperative new-onset chronic kidney disease (CKD) after partial nephrectomy were assessed., Results: A total of 185 patients with a mean tumor size of 2.6 cm (median 2.3, range 0.5-10) were identified. Mean ischemia time was 21.5 min. The last DTPA renal scan was performed at a mean follow-up duration of 23.3 months after surgery, and the mean decrease in GFR was 8.1 ml/min. By multivariable analysis, preoperative GFR (β = -039; p < 0.001), RENAL complexity score (β = -5.32; p < 0.001), and C-index complexity (β = -5.19; p < 0.001) were independent predictors of decreased GFR on DTPA. Of 175 patients in whom preoperative estimated GFR (eGFR) was > 60 ml/min/1.73 m(2), CKD developed in 14 (8 %) patients after surgery. Independent factors predicting new-onset CKD were preoperative eGFR (odds ratio [OR] 0.91; p = 0.047), age (OR 1.13; p = 0.003), and diabetes (OR 5.10; p = 0.038)., Conclusions: Although each scoring system describing the complexity of renal tumors correlates with change in GFR after partial nephrectomy, RENAL and C-index score were significantly predictive of GFR reduction.

Objective: To evaluate the efficacy and safety of sorafenib for Korean patients with metastatic renal cell carcinoma (mRCC)., Methods: A total of 177 mRCC patients using sorafenib as first- (N = 116), second- (N = 43), and third-line (N = 18) therapies were enrolled from 11 Korean centers between 2006 and 2012. The patient characteristics, therapy duration, tumor response, disease control rate, and tolerability were assessed at baseline and at routine follow-ups, and the progression-free survival (PFS) and overall survival (OS) times and rates were analyzed., Results: Among all patients, 18 (10.2%) stopped sorafenib treatment for a median of 1.7 weeks, including 15 (8.5%) who discontinued the drug, while 40 (22.6%) and 12 (6.8%) patients required dose reductions and drug interruptions, respectively. Severe adverse events (AEs) or poor compliance was observed in 64 (36.2%) patients, with 118 (7.4%) ≥grade 3 AEs. During the treatment, one myocardial infarction was observed. The number of ≥grade 3 AEs in the first-line sorafenib group was 71 (6.8% of the total 1048 AEs). During a median follow-up of 17.2 months, the radiologically confirmed best objective response rate, disease control rate, median PFS, and median OS were 22.0%, 53.0%, 6.4 months (95% confidence interval [CI], 5.2-8.9), and 32.6 months (95% CI, 27.3-63.8) for the total 177 sorafenib-treated patients, respectively, and 23.2%, 56.0%, 7.4 months (95% CI, 5.5-10.5), and not reached yet (95% CI, 1.0-31.1) for the first-line sorafenib group, respectively., Conclusions: Sorafenib produced tolerable safety, with a ≥grade 3 AE rate of 7.4% and an acceptable disease control rate (53.0%) in Korean mRCC patients.

Objectives: To evaluate the association between ABO blood group and prognosis in patients with renal cell carcinoma (RCC) undergoing surgery., Materials and Methods: A review of the nephrectomy database of the Asan Medical Center identified 3,172 consecutive patients who underwent nephrectomy for RCC between 1997 and 2012. Patients were followed up for a median 60.2 months (interquartile range 33-102 months). Recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS) were calculated by the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazards regression model was used to estimate the prognostic significance of each variable., Results: Of these 3,172 patients, 915 (28.8 %), 1,057 (33.7 %), 860 (26.7 %) and 340 (10.8 %) were blood types O, A, B, and AB, respectively. ABO blood group was not associated with age, sex, operation method, American Society of Anesthesiologists physical status classification, histologic subtype, or pathological TNM stage. The 5-year OS rates in patients with blood types O, A, B, and AB were 86.0, 86.8, 86.6, and 88.6 %, respectively, and the 10-year OS rates were 78.7, 78.6, 79.1, and 76.9 %, respectively (P = 0.990). ABO blood group was not significantly associated with RFS (P = 0.921) or CSS (P = 0.808). Univariable and multivariable analyses showed that ABO blood group was not a significant prognostic factor of RFS, CSS, or OS., Conclusions: Our study found that ABO blood group is not associated with survival outcomes and is not a prognostic factor in patients who underwent surgery for RCC.

Purpose: The objective was to investigate the impact of statin use on prognosis after radical nephroureterectomy for upper urinary tract urothelial carcinoma (UTUC)., Materials and Methods: A retrospective review of medical records identified 277 patients who underwent radical nephroureterectomy for primary UTUC at Asan Medical Center between January 2006 and December 2011. Information on preoperative statin use was obtained from patient charts in an electronic database. We assessed the impact of statin use on recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS)., Results: Of these 277 patients, 62 (22.4%) were taking statin medications. Compared to the statin nonusers, the statin users were older, had a higher body mass index, and had higher rates of cardiovascular disease and diabetes. The 5-year RFS rates of statin users and nonusers were 78.5% and 72.5%, respectively (p=0.528); the 5-year CSS rates were 85.6% and 77.7%, respectively (p=0.516); and the 5-year OS rates were 74.5% and 71.4%, respectively (p=0.945). In the multivariate analysis, statin use was not an independent prognostic factor for RFS (hazard ratio, 0.47; p=0.056), CSS (hazard ratio, 0.46; p=0.093), or OS (hazard ratio, 0.59; p=0.144) in patients who underwent radical nephroureterectomy for UTUC., Conclusions: Statin use was not associated with improved RFS, CSS, or OS in the sample population of patients with UTUC.

Purpose: Despite several therapeutic options renal cell carcinoma is associated with a poor clinical outcome. Therefore, we investigated whether combining 5-fluorouracil with the histone deacetylase inhibitor belinostat would exert a synergistic effect on renal cell carcinoma cells in vitro and in vivo., Materials and Methods: We used SN12C cells treated with 5-fluorouracil and/or belinostat in vitro and in xenograft experiments in vivo. Cell viability and death mechanisms were assessed by MTS assay and Western blot. To investigate the role of reactive oxygen species we used H2DCF-DA, reactive oxygen species scavengers and the roGFP2 construct., Results: Belinostat potentiated the anticancer effect of 5-fluorouracil. It synergistically induced apoptosis by activating caspases and increasing the subG1 cell population. Effects on reactive oxygen species mediated DNA damage included decreased thioredoxin expression and increased levels of TBP-2, γ-H2AX and Ac-H3. Furthermore, belinostat attenuated the 5-fluorouracil mediated induction of thymidylate synthase via HSP90 hyperacetylation. Co-administration of 5-fluorouracil with belinostat similarly reduced tumor volume and weight, and increased γ-H2AX and Ac-H3 levels in the SN12C xenograft model., Conclusions: In combination with 5-fluorouracil the targeted inhibitor of histone deacetylase synergistically inhibited renal cancer cell growth by the blockade of thymidylate synthase induction and the induction of reactive oxygen species mediated DNA damage in vitro and in vivo. Our results suggest that combined treatment with belinostat and 5-fluorouracil may represent a promising new approach to renal cancer., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Magnetic resonance imaging (MRI) is a diagnostic imaging method that can be used to assess indeterminate renal masses on computed tomography (CT) scans. We evaluated the diagnostic accuracy of MRI in distinguishing renal cell carcinoma (RCC) from indeterminate renal masses on CT scans and investigated the impact of MRI on clinical decision making., Methods: A retrospective study was conducted in 120 patients who underwent MRI to distinguish RCC from indeterminate renal masses on CT scans. The diagnostic accuracies of CT and MRI were compared, and factors associated with a final diagnosis of RCC were evaluated using multivariate logistic regression analysis., Results: Of the 120 patients, 47 (39.2%) had benign masses, including 32 (26.7%) angiomyolipomas, 5 (4.2%) oncocytomas, and 10 (8.3%) complicated cysts. The specificity of MRI was significantly superior to that of CT in diagnosing RCC (68.1 vs. 27.7%, p = 0.001), whereas their sensitivities were equivalent (91.8 vs. 94. 5%, p = 0.754). Multivariate analysis showed that female gender [odds ratio (OR) 0.11, p < 0.001] and MRI diagnosis of RCC (OR 23.35, p < 0.001) were independently associated with a final diagnosis of RCC. MRI results showed that 15 patients (12.5%) thought to have RCC on CT scans could have avoided unnecessary surgery, whereas three patients (2.5%) thought to have benign masses on CT scans could have undergone appropriate surgery., Conclusions: MRI has incremental benefit to distinguish RCC from indeterminate renal masses on CT scans. MRI may help to decide the most appropriate treatment strategy for patients with indeterminate renal masses on CT scans.

Purpose: We investigated the proportion of regulatory T cells (Treg cells) in the peripheral blood (PB) and among tumor-infiltrating lymphocytes (TILs) of patients with renal cell carcinoma (RCC) compared with age-matched healthy controls (HCs). We also assessed the presence of several immunomodulatory cytokines in these patients., Methods: The proportion of Treg cells in the PB of 59 patients with clinically localized RCC and 65 HCs, as well as the prevalence of Treg cells among TILs and lymphocytes in normal kidney tissue, were evaluated by flow cytometry using specific monoclonal antibodies recognizing CD4(+), CD25(+), and Foxp3(+) markers. In addition, the levels of transforming growth factor (TGF)-β1, interleukin-6, tumor necrosis factor-α, and interferon-γ were determined using standard enzyme-linked immunosorbent assay., Results: There was no difference between the mean percentage of Treg cells in the PB of patients with RCC and HCs (P = 0.148). However, the proportion of Treg cells showed a significant positive correlation with tumor size (r = 0.295, P = 0.029), with the percentage of PB Treg cells significantly higher in patients with RCC with large tumors (≥7 cm) than in HCs (4.6 ± 5.8% vs. 1.9 ± 2.6%, P = 0.023). There was no statistically significant difference in the percentage of Treg cells among TILs and lymphocytes in normal kidney tissue (P = 0.629). The mean TGF-β1 level in patients with RCC was statistically significantly higher than in HCs (P<0.001)., Conclusions: In this study, we provide evidence for an increased proportion of Treg cells in the PB of clinically localized patients with RCC with substantial tumor burden and a higher level of TGF-β1 compared with age-matched HCs., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: Xp11.2 translocation renal cell carcinoma (RCC) is characterized by various translocations of the TFE3 transcription factor gene. These rare cancers occur predominantly in children and young adults. Here, we review the clinicopathological features of Xp11.2 translocation RCC., Materials and Methods: We identified 21 patients with Xp11.2 translocation RCC. We retrospectively analyzed patient characteristics, clinical manifestations, and specific pathological features to assess definitive diagnosis, surgical and systemic treatments, and clinical outcomes., Results: The mean age at diagnosis was 43.4±20.0 years (range, 8-80 years; 8 males and 13 females). Eleven patients were incidentally diagnosed, nine patients presented with local symptoms, and one patient presented with systemic symptoms. The mean tumor size was 6.2±3.8 cm (range, 1.9-14 cm). At the time of diagnosis, 11, 1, and 5 patients showed stage I, II, and III, respectively. Four patients showed distant metastasis. At analysis, 15 patients were disease-free after a median follow-up period of 30.0 months. Four patients received target therapy but not effectively., Conclusions: Xp11 translocation RCC tends to develop in young patients with lymph node metastasis. Targeted therapy did not effectively treat our patients. Surgery is the only effective therapy for Xp11 translocation RCC, and further studies are needed to assess systemic therapy and long-term prognosis.

Introduction: We analyzed the clinicopathological data of patients undergoing radical nephrectomy for clear cell type renal cell carcinoma (RCC) who presented with metastasis and were subsequently treated with sunitinib and identified molecular markers in nephrectomy specimens to predict susceptibility to sunitinib., Patients and Methods: The medical records of 65 patients who underwent nephrectomy for metastatic clear cell type RCC and were then treated with sunitinib were reviewed. The nephrectomy specimens were subjected to prospective immunohistochemical staining for vascular endothelial growth factor, vascular endothelial growth factor receptor-2 (VEGFR-2), platelet-derived growth factor-B, and platelet-derived growth factor receptor-β expression., Results: In 58 evaluable patients, the median value of initial and best overall response was -9.69 and -24.04 %, respectively. VEGFR-2 expression was associated significantly with initial and best overall responses to sunitinib, along with Karnofsky performance status and Memorial Sloan-Kettering Cancer Center prognostic risk group. Multiple linear regression analyses revealed that strong VEGFR-2 expression was positively associated with the best reduction in tumor response (β = -0.275, P = 0.016) and poor Karnofsky performance status was negatively associated it (β = 0.477, P < 0.001). Karnofsky performance status and retroperitoneal lymph node involvement associated independently with progression-free- and overall survivals. None of the molecular markers associated significantly with survival., Conclusion: VEGFR-2 expression might be a useful biomarker for predicting the response to sunitinib by patients with metastatic RCC. Karnofsky performance status and retroperitoneal lymph node involvement were predictive of disease progression and death.

Objective: The aim of the study is to identify pre-operative variables for selection of patients who would benefit from upfront cytoreductive nephrectomy for metastatic renal cell carcinoma., Methods: We reviewed the medical records of 171 patients who were presented with synchronous metastatic renal cell carcinoma and who had received no systemic therapy before enrollment. Of these, 96 underwent cytoreductive nephrectomy followed by targeted therapy (cytoreductive nephrectomy group) and 75 treated with targeted therapy alone (non-cytoreductive nephrectomy group). A Cox proportional hazards regression model was used to estimate the prognostic significance of pre-operative characteristics predicting overall survival in the cytoreductive nephrectomy group. The significant variables were designated as pre-operative factors to identify patients who would benefit from cytoreductive nephrectomy., Results: The median overall survival was 19.9 and 11.7 months in the cytoreductive nephrectomy and non-cytoreductive nephrectomy groups (P < 0.001). Karnofsky performance status (<80; hazard ratio 9.497, P < 0.001), hemoglobin (less than lower limit of normal; hazard ratio 1.913, P = 0.025), neutrophils (greater than upper limit of normal; hazard ratio 6.533, P < 0.001) and clinical N stage (N2; HR 2.714, P = 0.001) were independent pre-operative risk factors of mortality. Only those patients with risk factor <2 who had undergone upfront cytoreductive nephrectomy had a better median overall survival than patients who received targeted therapy alone (28.2 vs. 18.4 months, P = 0.018)., Conclusions: Four pre-operative risk factors (Karnofsky performance status, hemoglobin, neutrophils and clinical N stage) were identified as suitable for selection of patients who would not benefit from undergoing cytoreductive nephrectomy., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: We investigated the prognostic significance of tumor location at the renal hilum near the sinus structure on the recurrence in T1 renal cell carcinoma (RCC)., Methods: A total of 1,818 T1 RCC patients who underwent radical (RN) or partial nephrectomy (PN) from 1997 to 2011 were retrospectively reviewed. A hilar tumor was defined as a tumor abutting the main renal artery and/or vein or its segmental branches, without invasion. We compared the recurrence-free survival (RFS) rates between hilar and nonhilar T1 RCC and analyzed predictors of RFS after nephrectomy., Results: Patients with hilar tumors showed a poorer 5-year RFS compared with nonhilar tumors both in T1a (89.7 vs. 98.5 %, p < 0.001) and T1b (81.6 vs. 95.1 %, p < 0.001) RCCs. Among patients who underwent RN and PN, hilar tumors were associated with lower 5-year RFS (87.6 vs. 97.2 % for RN, 78.1 vs. 98.2 % for PN, both p < 0.001). In T1a hilar tumor, PN was associated with poorer 5-year RFS than RN (79.5 vs. 93.0 %, p < 0.001). In multivariate analysis, a hilar location remained as an independent predictor of recurrence in both T1a and T1b tumors (both p = 0.001)., Conclusions: Hilar tumors show a higher recurrence rate than nonhilar counterparts in T1 RCC. In T1a hilar tumors, PN demonstrated poorer RFS than RN. Potential intrinsic renal anatomical or lymphovascular structural differences as well as differences in cancer characteristics need further investigations.

Background: This study aimed to compare the changes in kidney function and the association of tumor size and renal outcomes between patients with renal cell carcinoma (RCC) who underwent radical nephrectomy (RN) and those who underwent partial nephrectomy (PN)., Methods: A retrospective cohort study was conducted for 557 patients with an RCC of ≤7 cm in diameter and normal contralateral kidney function who underwent PN or RN. PN was performed for 218 (39%) patients. Renal outcomes included the incidence of acute kidney injury (AKI), new-onset chronic kidney disease (CKD), and a ≥25% decline in eGFR 1 year after surgery., Results: Serial changes in eGFR were compared during the 3 years of follow-up. Postoperative eGFR was significantly lower in patients undergoing RN than in those undergoing PN. The incidence of AKI and new-onset CKD was significantly higher in patients after RN (70.1% vs. 24.3%, respectively; P<0.001) than after PN (55.7% vs. 6.2%, respectively; P<0.001). According to the multivariable logistic regression analysis, RN was an independent risk factor for a ≥25% decline in kidney function after 1 year regardless of the tumor size, even after adjusting for various covariates., Conclusions: Compared to PN, RN for even a moderate sized RCC leads to an increased incidence of AKI and new-onset CKD, and is a significant risk factor for kidney function decline. Therefore, PN should be considered as the choice of surgical treatment for RCCs that are ≤7 cm in diameter in order to preserve renal function postoperatively.

Purpose: We aimed to investigate the correlations between the expression of VEGF, PDGF-B, and their receptors (VEGFR2 and PDGFR-β) with pathologic stage or cell type in non-metastatic renal cell carcinoma., Materials and Methods: VEGF, VEGFR2, PDGF-B, and PDGFR-β protein expression were evaluated immunohistochemically in prospectively collected 1,423 tumour samples obtained during radical or partial nephrectomy at a tertiary referral center. Intensity of expression was quantified on a scale of 0 to 3, and was compared among renal cell carcinoma cell types., Results: The study cohort consisted of 1,091 patients, of mean age 54 years, including 968 (88.7%) with clear cell, 82 (7.5%) with papillary, 31 (2.8%) with chromophobe, 4 (0.4%) with unclassified, and 6 (0.5%) with other types of renal cell carcinoma. VEGF expression increased with higher T and N stage and Fuhrman nuclear grade. PDGFR-β expression was highest in clear cell renal cell carcinoma, whereas VEGF and PDGF-B expression were highest in papillary renal cell carcinoma. After adjusting for T stage and Fuhrman nuclear grade using multivariate logistic regression analysis, VEGF (OR = 3.57, P < 0.001), VEGFR2 (OR = 1.82, P = 0.017), and PDGF-B (OR = 2.46, P = 0.019) expression were significantly greater in papillary than in clear cell type., Conclusions: Our results indicate that the cytoplasmic expression of VEGF, VEGFR2, PDGF-B, and PDGFR-β in RCC tumour cells is different in various pathologic stage and cell type. Notably, VEGF and PDGF-B expression are higher in papillary than in clear cell renal cell carcinoma. Further studies using quantitative measurement of proangiogenic factors in tumour cell are needed.

Aim: The aim of the present study was to evaluate how treatment with everolimus changes readouts of the pulmonary function test (PFT) in patients with metastatic renal cell carcinoma (mRCC). We also attempted to determine whether changes of PFT or everolimus-associated non-infectious pneumonitis (NIP) might affect the efficacy of everolimus., Materials and Methods: The results of PFTs, radiological reports and medical records of 36 mRCC patients treated with everolimus after failure to vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI) were reviewed., Results: Whereas 9 patients (30%) developed radiological changes consistent with everolimus-associated NIP (pneumonitis group), 27 were included in the non-pneumonitis group. The baseline value of the diffusing capacity for carbon monoxide divided by the alveolar volume (DLco/VA) was 90%. It decreased significantly as the duration of treatment increased (p<0.01). There was no significant difference in DLco/VA values between patients with and without NIP either at baseline (p=0.28) and 6 weeks after the initiation of everolimus therapy (p=0.18). The changes in DLco/VA between baseline and 6 weeks did not differ between the two groups (p=0.55). Time-dependent covariate Cox analysis, indicated that the decrease in DLco/VA was not correlated with the efficacy of everolimus in terms of progression-free survival (PFS; HR=1.0, p=0.94) and overall survival (OS; HR=0.98, p=0.18), whereas development of NIP was associated with worse PFS (HR=4.60, p=0.01)., Conclusion: Patients with mRCC who are receiving everolimus therapy display a reduction in DLco/VA over time. However, neither the baseline DLco/VA nor the change in DLco/VA over time can help predict either development of NIP or the efficacy of everolimus., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Objectives: To evaluate the prognostic significance of the Choi criteria for assessing the responses of a renal mass and inferior vena cava (IVC) tumor thrombus in patients with renal cell carcinoma (RCC) receiving targeted therapy., Materials and Methods: We reviewed the medical records of 22 patients diagnosed with RCC and IVC thrombus between 2005 and 2012. The efficacy of targeted therapy in renal mass and IVC tumor thrombus was evaluated using response evaluation criteria in solid tumors (RECIST) and Choi criteria, respectively. Overall survival was estimated, and the prognostic significance of each variable was estimated using Cox proportional-hazards regression modeling., Results: There were no significant differences in overall survival between patients with partial response (PR) and nonresponse according to RECIST criteria (19.3 vs 43 months; p = 0.212) or Choi criteria (9.0 vs 23.3 months; p = 0.109) in primary tumor. Regarding the response of IVC tumor thrombi, according to Choi criteria, nine patients (40.9 %) demonstrated PR and longer survival than patients with stable disease (7.2 vs 23.3 months; p = 0.014). In multivariable analysis, response to IVC thrombus according to Choi criteria was the only significant predictive factor. Patients with IVC thrombus who demonstrate the PR according to Choi criteria were at 0.35-fold greater overall risk of death compared with patients who did not demonstrate this response (p = 0.043)., Conclusions: A response according to Choi criteria in IVC tumor thrombus was an independent prognostic predictor in patients with RCC and IVC thrombus who receive targeted therapy.

Background and Objectives: To evaluate the impact of surgery on the prognosis of metastatic renal cell carcinoma (mRCC) with inferior vena cava (IVC) thrombus., Methods: In this retrospective study, the medical records of 45 patients who presented with synchronous mRCC with IVC thrombus, between 2005 and 2012, were reviewed. Twenty-eight patients underwent radical nephrectomy with IVC thrombectomy followed by targeted therapy (group 1) and 17 received targeted therapy alone (group 2). Cox proportional hazards regression models served to estimate the prognostic significance of variables., Results: The median progression-free survival of group 1 and group 2 was 4.1 and 3.5 months, respectively (P = 0.672). Their median overall survival was 17.3 and 19.7 months, respectively (P = 0.353). Multivariate analysis revealed that non-clear cell type RCC (HR = 3.46, P = 0.007) and lymph node metastasis (HR = 2.31, P = 0.003) independently predicted progression-free survival, and Karnofsky performance status (HR = 3.82, P = 0.013) and non-clear cell type RCC (HR = 4.01, P = 0.003) independently predicted overall survival. Surgical resection of the primary renal mass with IVC thrombus did not affect the probability of progression or overall mortality., Conclusions: Our limited data set would suggest a limited role for surgery in this patient population and that a prospective study in this group may define the role of surgery., (© 2014 Wiley Periodicals, Inc.)

Objectives: To evaluate the effect of renal cell carcinoma (RCC) on survival in von Hippel-Lindau (VHL) disease and to assess the relationship between tumor size and survival., Materials and Methods: In this retrospective cohort study, the medical records of 72 patients who presented with VHL disease between 1994 and 2012 were reviewed. Clinical VHL-related characteristics were analyzed, and the prognostic value of renal tumor size for overall survival was assessed by using Cox regression models., Results: Of the 72 VHL patients, 42 (58.3 %) and 30 (41.7 %) were male and female, respectively. The mean age was 37.9 years, and the median follow-up period was 61.5 months. In terms of VHL-related manifestations, 40 (55.6 %) had RCC, 46 (63.8 %) had hemangioblastoma in the cerebellum, 10 (13.9 %) had hemangioblastoma in the spinal cord, 34 (47.2 %) had a pancreatic mass, 18 (25.0 %) had pheochromocytoma, and 14 (19.4 %) had retinal capillary hemangioma. RCC was a major cause of mortality: Of the 11 patients who died, nine (12.5 %) died due to RCC progression. The 5-year overall survival rate was 85.6 % for all patients, 96.9 % for patients without RCC, 83.6 % for patients with RCC < 3 cm, and 75.8 % for patients with RCC ≥ 3 cm. Multivariable analysis showed that RCC ≥ 3 cm was an independent predictor of overall survival (HR 9.87, 95 % CI 1.17-83.00, p = 0.035) along with age (HR 1.05, 95 % CI 1.01-1.10, p = 0.027)., Conclusions: Renal tumor size was an independent prognostic factor for overall survival in VHL disease. This observation will be helpful for planning RCC treatment in VHL disease.

Purpose: To compare the outcomes of nephron-sparing options (e.g., partial nephrectomy [PN]) and low-surgical-morbidity options (e.g., radical nephrectomy [RN]) in elderly patients with limited life expectancy., Materials and Methods: We retrospectively reviewed 135 patients aged 70 years or older who underwent RN (n=82) or PN (n=53) for clinical T1 stage renal masses between January 2000 and December 2012. Clinicopathologic data were thoroughly analyzed and compared between the RN and PN groups. The modification of diet in renal disease equation was used to estimate glomerular filtration. Overall survival and cardiac events were assessed by using Kaplan-Meier survival analysis and Cox proportional-hazards regression modeling., Results: Over a median follow-up period of 59.72 months, 17 patients (20.7%) in the RN group and 3 patients (5.7%) in the PN group died. Chronic kidney disease (<60 mL/min/1.73 m(2)) developed more frequently in RN patients than in PN patients (75.6% vs. 41.5%, p<0.001). The 5-year overall survival rate did not differ significantly between the RN and PN groups (90.7% vs. 93.8%; p=0.158). According to the multivariate analysis, the Charlson comorbidity index score was an independent predictor of overall survival (hazard ratio [HR], 2.679, p=0.037). Type of nephrectomy was not significantly associated with overall survival (HR, 2.447; p=0.167) or cardiac events (HR, 1.147; p=0.718)., Conclusions: Although chronic kidney disease was lower after PN, overall survival and cardiac events were similar regardless of type of nephrectomy.

Purpose: To elucidate the reasons for conflicting results regarding the prognostic significance of tumor location in upper tract urothelial carcinoma (UTUC), we analyzed the stage-specific impact of tumor location on oncological outcomes following radical nephroureterectomy (RNU)., Methods: Data from 392 patients who underwent RNU with curative intent between 1991 and 2010 were reviewed. Prognostic impact of tumor location and various clinicopathological factors for recurrence-free survival (RFS) and cancer-specific survival (CSS) was evaluated using Kaplan-Meier and Cox regression analyses at each pathological stage. Tumor location was classified as renal pelvis or ureter, and pT3 tumors were further stratified as invading the renal parenchyma or peripelvic or periureteral fat., Results: In stage-specific analysis, tumor location did not have prognostic significance in patients with ≤pT2 tumors, whereas RFS and CSS rates were significantly lower in patients with pT3 ureteral tumors than renal pelvic tumors. Subgroup analysis showed that RFS and CSS rates were significantly higher for pT3 tumors invading the renal parenchyma than the peripelvic or periureteral fat. On multivariate analysis in pT3 tumors adjusting other clinicopathological parameters, tumor location remained significant predictors for both RFS and CSS. Compared with tumors invading renal parenchyma, tumors invading peripelvic fat or periureteral fat were associated with about 3.5 times higher risk for cancer-specific mortality (p < 0.05)., Conclusions: Location-dependent survival difference exists only in patients with pT3 UTUC. Conflicting institutional results regarding tumor location in UTUC may be due to difference in the proportions of parenchymal versus peripelvic fat invasion in pT3 pelvic tumors.