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Purpose: Few studies have demonstrated the clinical significance of pretreatment serum albumin and globulin in prostate cancer (PCa). This study evaluated the association between the pretreatment albumin to globulin ratio (AGR) and clinicopathologic characteristics of nonmetastatic PCa in a large multicenter setting in Korea., Materials and Methods: This study involved 742 patients with nonmetastatic PCa who underwent radical prostatectomy (RP) in seven institutions between January 2011 and December 2012. The AGR was calculated as follows: albumin/(total protein-albumin). Patients were divided into low and high AGR groups by a cutoff value from a receiver operating characteristic curve analysis., Results: The best cutoff for the AGR was set at 1.53. The area under the curve of the AGR was 0.624 (95% confidence interval, 0.557-0.671; p<0.001). Patients who had a lower pretreatment AGR (<1.53) were identified as the low AGR group (n=398, 53.6%) and the remaining patients as the high AGR group (n=344, 46.4%). Preoperative AGR was significantly lower in patients with non-organ-confined disease (≥pT3) than in those with organ-confined disease (≤pT2) (p<0.001). The low AGR group had higher aggressive pathologic Gleason scores (pGS) (≥8) than did the high AGR group (p=0.016). Furthermore, the AGR was an independent prognostic factor for high pGS (≥8) and non-organ-confined disease (≥pT3), according to multivariate logistic regression analysis., Conclusions: A low AGR was closely associated with nonconfined disease (≥pT3) and high pGS (≥8). AGR can be a useful serological marker for predicting adverse pathology in patients with nonmetastatic PCa who undergo RP., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association, 2021.)

Purpose: P21-activated kinase 4 (PAK4), a serine/threonine kinase that regulates a number of fundamental cellular processes, has been suggested as a prognostic factor for various human tumors. The aim of the present study was to evaluate the clinical implications of phospho-Ser474 PAK4 (pPAK4 S474 ), an activated form of PAK4, in surgically treated renal cell carcinoma (RCC)., Materials and Methods: Samples from 131 patients with surgically treated RCC were immunostained to detect PAK4 and pPAK4 S474 . Expression of PAK4 and pPAK4 S474 was compared with clinicopathological characteristics and survival after nephrectomy., Results: PAK4 and pPAK4 S474 were expressed predominantly in the nucleus. Overall, 57.3% (75/131) and 24.4% (29/119) of specimens exhibited high expression of pPAK4 S474 and PAK4, respectively. High expression of pPAK4 S474 was associated with adverse pathologic characteristics, including advanced tumor stage and grade (p=0.036 and p=0.002, respectively), whereas this association was not significant for PAK4 expression (each p>0.05). Kaplan-Meier estimates showed that high expression of pPAK4 S474 was associated with shorter recurrence-free survival in a subgroup with localized RCC and with cancer-specific survival in the total RCC cohort (log-rank test: p=0.001 and p=0.005, respectively), whereas PAK4 expression was not. Multivariate Cox regression analysis identified that high pPAK4 S474 expression was an independent predictor of recurrence in the subgroup with localized RCC., Conclusions: pPAK4 S474 may be a more accurate prognostic factor than total PAK4 in RCC patients. This marker would be useful for identifying patients with pathologically localized disease who may require further interventions., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association, 2021.)

The bladder cancer (BCa) microenvironment comprises heterogeneous tumor cell populations, the surrounding stroma and the extracellular matrix (ECM). Collagen, the scaffold of the tumor microenvironment, regulates ECM remodeling to promote tumor infiltration, angiogenesis, invasion and migration. The present study examined how collagen type VI‑α (COL6A) 1 and 2 function during BCa pathogenesis and progression, with the aim of facilitating the development of precision therapeutics, risk stratification and molecular diagnosis. COL6A1 and COL6A2 mRNA expression in non‑muscle invasive BCa (NMIBC) and MIBC tissue samples was measured using reverse transcription‑quantitative PCR. In addition, the tumor‑suppressive effects of COL6A1 and COL6A2 in human BCa EJ cells (MGH‑U1) were assessed. Compared with normal controls, COL6A1 and COL6A2 mRNA expression was downregulated in both NMIBC and MIBC tissue samples (P<0.05, respectively). COL6A1 and COL6A2 effectively inhibited the proliferation of human BCa EJ cells (MGH‑U1) and induced cell cycle arrest at the G 1 phase. Additionally, COL6A1 and COL6A2 served roles in MAPK and AKT signaling by increasing p38 MAPK phosphorylation and decreasing AKT phosphorylation. Finally, COL6A1 and COL6A2 inhibited wound healing and invasion by suppressing the activity of matrix metalloproteinase (MMP)‑2 and MMP‑9. In conclusion, COL6A1 and COL6A2 may act as classical collagens by forming a physical barrier to inhibit BCa tumor growth and invasion.

Background: Recent reports show that the pre-operative or post-operative skeletal mass index (sarcopenia) affects survival rates for various cancers; however, the link between prostate cancer survival and sarcopenia is unclear. Therefore, this study examined the effect of the pre-operative internal obturator muscle (IOM) mass index on biochemical recurrence (BCR) of prostate cancer (PCa) patients who underwent radical prostatectomy., Methods: In total, 222 patients, who underwent open, laparoscopic, or robot-assisted radical prostatectomy at seven centers in 2011 and were followed up for 5 years, were enrolled. BCR was examined in the context of pre-operative IOM mass index and BMI., Results: The mean age of the patients was 67.82 ± 6.23 years, and the mean pre-operative prostate-specific antigen (PSA) level was 11.61 ± 13.22 ng/ml. There was no significant difference in baseline characteristics between the low and high IOM mass index groups (p > 0.05). Age, pre-op PSA level, ECE, and T-stage were associated with BCR (p = 0.049, p < 0.001, p = 0.001, p = 0.004, respectively). BMI, prostate volume, Gleason score, resection margin, N-stage, M-stage and IOM mass index was not associated with BCR (p > 0.05)., Conclusions: Pre-operative IOM mass index was not associated with BCR; however, long-term follow-up is necessary to evaluate cancer-specific and overall survival of PCa patients.

Purpose: MicroRNAs (miRNAs) are small non-coding RNAs and are involved in the development, proliferation, and pathogenesis of prostate cancer (PCa). Urinary miRNAs are promising non-invasive biomarkers for PCa diagnosis because of their stability in urine. Here, we evaluated the diagnostic value of urinary miR-1913 to miR-3659 ratio in PCa patients and benign prostate hyperplasia (BPH) controls., Materials and Methods: Candidate miRNAs were identified from urinary microarray data and tested by real-time PCR. The urinary miR-1913 to miR-3659 expression ratio was selected and tested in 83 urine samples (44 PCa and 39 BPH) to confirm its validity as a non-invasive diagnostic biomarker for PCa., Results: The expression ratio of urinary miR-1913 to miR-3659 was significantly higher in PCa than in BPH (p=0.002) and showed a higher area under the receiver operating characteristic curve than prostate-specific antigen (PSA; 0.821 vs. 0.518) in patients within the PSA gray zone (tPSA: 3-10 ng/mL), with sensitivity of 75.0% and specificity of 78.6% (p=0.003)., Conclusions: The urinary miR-1913 to miR-3659 expression ratio was increased in PCa and may serve as a useful supplemental biomarker to PSA for the diagnosis of PCa, particularly in patients within the PSA gray zone., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association, 2021.)

Background: There is an increasing demand for prognostic immune biomarkers of cancer. The prognostic significance of immune markers has been shown for various cancers, but biomarkers of bladder cancer (BCa) have not been fully evaluated. To clarify the role of human leukocyte antigen DR alpha chain (HLA-DRA) in BCa development, we examined expression of HLA-DRA mRNA in tissue samples of non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC)., Materials and Methods: Tissues of 96 NMIBC, 43 MIBC and 59 controls comprising noncancerous BCa surrounding tissues were used to examine the expression of HLA-DRA gene by real-time polymerase chain reaction. The expression of up-stream genes regulating HLA-DRA were also measured to explain the role of HLA-DRA in BCa., Results: Patients with high grade NMIBC showed higher expression of HLA-DRA than those with low grade NMIBC (P < 0.05). In addition, NMIBC patients who progressed to MIBC showed high expression of HLA-DRA mRNA. Kaplan-Meier analysis showed that NMIBC patients with low expression of HLA-DRA had better progression-free survival than those with high expression (P = 0.004). Moreover, the expression of genes regulating HLA-DRA varied in NMIBC and MIBC, indicating a different immunoregulation effect of HLA-DRA in both cancers., Conclusions: High expression of HLA-DRA in NMIBC patients has implications for patient stratification strategies, as well as for BCa tumor immunology., Competing Interests: Conflict of interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Basal metabolic rate (BMR) is an indicator of overall body metabolism and may portend unique aberrations in urine physico-chemistry and stone recurrence. The present study examined the effect of predicted BMR on 24 hours urinary metabolic profiles and stone recurrence in obese stone patients., Materials and Methods: Data from 308 obese patients (body mass index [BMI] ≥30 kg/m²) diagnosed with urinary stone disease between 2003 and 2015 were analyzed retrospectively. BMR was calculated using the Harris-Benedict equation, and patients were classified into two predicted BMR categories (<1,145 kcal/day, ≥1,145 kcal/day). Urinary metabolic parameters and risk of stone recurrence were compared between the two groups., Results: The high BMR group was more likely to be younger and female, and to have a high BMI and lower incidence of diabetes than the low BMR group (each p<0.05). There was a positive correlation between BMR and 24 hours urinary sodium, uric acid, and phosphate excretion. The amounts of stone-forming constituents such as calcium and uric acid were significantly higher in the high BMR group. Kaplan-Meier estimates showed that the high BMR group had a significantly shorter stone recurrence-free period than the low BMR group (log-rank test, p<0.001). Multivariate Cox regression analyses revealed that predicted BMR was an independent factor of stone recurrence (hazard ratio, 2.759; 95% confidence interval, 1.413-5.386; p=0.003)., Conclusions: BMR may be an easily measured parameter that can be used to identify risk of stone recurrence in obese stone patients., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association, 2021.)

Exhausted T cells in the tumor microenvironment are major targets of immunotherapies. However, the exhaustion status of CD8 + tumor-infiltrating lymphocytes (TILs) in bladder cancer has not been comprehensively evaluated. Herein, we examined distinct exhaustion status of CD8 + TILs based on the level of programmed cell death-1 (PD-1) and thymocyte selection-associated high mobility group box protein (TOX) expression in urothelial bladder cancer. We also evaluated the reinvigoration of exhausted CD8 + TILs upon ex vivo treatment with inhibitory checkpoint blockers. TOX-expressing PD-1 high CD8 + TILs had the highest expression of immune checkpoint receptors (ICRs), the most terminally exhausted features, and the highest tumor antigen reactivity among PD-1 + CD8 + TILs. Bladder cancer patients with a high percentage of PD-1 high TOX + CD8 + TILs had more progressed T-cell exhaustion features and higher programmed death-ligand 1 expression in tumor tissues. TIGIT was the most frequent co-expressed ICR on PD-1 + CD8 + TILs, and TIGIT blockade enhanced the PD-1 blockade-mediated cytokine production by CD8 + TILs from bladder cancer patients. Our findings provide an improved understanding of the heterogeneous exhaustion status of CD8 + TILs and additional immunotherapy strategies to improve outcomes of bladder cancer patients., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Non-muscle-invasive bladder cancer (NMIBC) is clinically heterogeneous; thus, many patients fail to respond to treatment and relapse. Here, we identified a molecular signature that is both prognostic and predictive for NMIBC heterogeneity and responses to Bacillus Calmette-Guérin (BCG) therapy. Transcriptomic profiling of 948 NMIBC patients identified a signature-based subtype predictor, MSP888, along with three distinct molecular subtypes: DP.BCG+ (related to progression and response to BCG treatment), REC.BCG+ (related to recurrence and response to BCG treatment), and EP (equivocal prognosis). Patients with the DP.BCG+ subtype showed worse progression-free survival but responded to BCG treatment, whereas those with the REC.BCG+ subtype showed worse recurrence-free survival but responded to BCG treatment. Multivariate analyses revealed that MSP888 showed independent clinical utility for predicting NMIBC prognosis (each p = 0.001 for progression and recurrence, respectively). Comparative analysis of this classifier and previously established molecular subtypes (i.e., Lund taxonomy and UROMOL class) revealed that a great proportion of patients were similar between subtypes; however, the MSP888 predictor better differentiated biological activity or responsiveness to BCG treatment. Our data increase our understanding of the mechanisms underlying the poor prognosis of NMIBC and the effectiveness of BCG therapy, which should improve clinical practice and complement other diagnostic tools.

Background: The present study investigated the association of serum parathyroid hormone (PTH), vitamin D, and calcium levels with prostate cancer (CaP)., Methods: The study population consisted of an experimental group [459 patients including 216 patients with CaP and 243 patients with benign prostate hyperplasia (BPH)] and a prostatectomy group (47 patients who underwent radical prostatectomy). Patients with serum creatinine levels >1.4 mg/dl, parathyroid disease, and/or PTH levels <10 pg/ml were excluded. Patients with CaP and patients with BPH were compared, and the correlation between serum parameters and clinical data was determined. Preoperative and postoperative PTH levels were compared in the prostatectomy group., Results: Mean PTH levels were 41.67 ± 28.82 and 27.06 ± 17.32 pg/ml in the CaP and BPH groups, respectively ( p  < 0.001). When patients were divided into two groups as per prostate-specific antigen levels (≤20 or >20 ng/ml), Gleason score (≤7 or ≥8), and stage (≤T3 or ≥ T4), there was no significant difference in PTH levels between the two groups. Mean postoperative PTH levels (26.93 ± 13.58 pg/ml) were significantly lower than preoperative PTH levels (36.71 ± 21.04 pg/ml) in the same patients who underwent radical prostatectomy., Conclusion: Serum PTH levels were higher in patients with CaP than in patients with BPH and decreased significantly after radical prostatectomy. The present results suggest an association between serum PTH and CaP. Further large cohort studies are necessary to validate the present data., Competing Interests: All authors have no conflict of interest to declare., (© 2020 Asian Pacific Prostate Society, Publishing services by Elsevier B.V.)

Background: The objective of this study was to provide more definitive information about the prognostic impact of perioperative blood transfusion (PBT) on patients with surgically treated renal cell carcinoma (RCC)., Methods: A database of 4019 patients with clear cell RCC, all of whom underwent radical or partial nephrectomy as primary therapy as part of a multi-institutional Korean collaboration between 1988 and 2015, was analyzed retrospectively. PBT was defined as transfusion of allogeneic red blood cells during surgery or postsurgical period. Receipt of a PBT, as well as the amount and time of blood transfusion (BT), was compared., Results: Overall, 335 (8.3%) patients received a PBT: 84 received postoperative BT, 202 received intraoperative BT, and 49 received both intraoperative and postoperative BT. Patients receiving a PBT had a poor preoperative immuno-nutritional status, and aggressive tumor characteristics. Multivariate analyses identified PBT as an independent predictor of recurrence-free survival and cancer-specific survival. Prognostic impact of PBT was restricted to those with locally advanced stage (pT3-4), and who underwent radical nephrectomy. Among patients who received a PBT, intraoperative (but not postoperative) BT was a prognostic factor for survival. Among patients who received intraoperative BT, those receiving three or more transfusion units had a significantly worse survival., Conclusion: Receipt of a PBT was an independent predictor of RFS and CSS in patients with surgically treated RCC, specifically locally advanced disease. Regarding the prognostic impact of timing or dose of PBT on survival, intraoperative BT and ≥ 3 pRBC units were associated with adverse oncological outcomes.

Screening for genes or markers relevant to bladder cancer (BC) tumorigenesis and progression is of vital clinical significance. The present study used reverse-transcription quantitative PCR reaction assays to examine the expression of mRNA encoding Rho GTPase-activating protein 9 (ARHGAP9) in BC tissue samples and to determine whether ARHGAP9 is an independent prognostic biomarker for non-muscle invasive BC (NMIBC) and muscle invasive BC (MIBC). The results revealed that the downregulation of ARHGAP9 expression in the tissue of patients with NMIBC or MIBC was significantly associated with a poor prognosis. In patients with NMIBC, a high expression of ARHGAP9 was significantly associated with prolonged recurrence-free survival, whereas in MIBC patients, it was significantly associated with an increased progression-free and cancer-specific survival. The risk of cancer-specific death was 2.923 times higher (95% confidence interval, 1.192-7.163) when ARHGAP9 levels were decreased. In conclusion, lower expressions of ARHGAP9 correlated with BC prognosis, indicating that it may be a useful marker for guiding treatment application., (Copyright: © Piao et al.)

Purpose: To investigated the prognostic significance of the geriatric nutritional risk index (GNRI) in patients with surgically treated clear cell renal cell carcinoma (ccRCC). Patients and methods: We retrospectively selected 4,591 consecutive patients with surgically treated ccRCC from a multi-institutional Korean collaboration between 1988 and 2015. The clinical significance of the GNRI as a continuous and categorical variable was determined. Results: Preoperative low GNRI was significantly associated with older age, low body mass index, presence of diabetes, poor performance status, and presence of symptoms at diagnosis, as well as pathologic features such as aggressive tumor characteristics including large tumor size, advanced stage, high nuclear grade, lymphovascular invasion, sarcomatous differentiation, and tumor necrosis. A low GNRI was significantly associated with a short recurrence-free survival (RFS) in localized (pT1-2N0M0) ccRCC and cancer-specific survival (CSS) in the entire cohort, and with short RFS and CSS in the subgroup analysis according to age categories (≤65 and >65 years). Multivariate Cox regression analysis showed that preoperative GNRI, as a continuous or categorical variable, was an independent predictor of RFS and CSS. Conclusion: Malnutrition as assessed by the preoperative GNRI is associated with aggressive tumor characteristics and poor survival in patients with surgically treated ccRCC.

Purpose: To determine the value of 24-h urine osmolality (UOsm) as a representative index of adequate hydration and predictor of stone recurrence in patients with urolithiasis., Methods: Medical records of consecutive patients presenting with renal or ureteric stones between 1994 and 2017 were retrospectively reviewed. Patients were grouped according to the results of 24-h UOsm (low ≤ 564 mOsm/kg H 2 O, high > 564 mOsm/kg H 2 O). Metabolic parameters and risk of stone recurrence were compared between the two groups., Results: The low urine concentration group were more likely to be older, to be female, and to have a lower body mass index and higher glomerular filtration rate than the high concentration group (each P < 0.005). A positive correlation was seen between 24-h UOsm and urinary calcium, sodium, uric acid, and magnesium excretion and 24-h specific gravity; a negative correlation was seen with 24-h urine volume. Stone-forming constituents, such as calcium and uric acid, were significantly higher in the high urine concentration group. Kaplan-Meier estimates showed that the low urine concentration group had a significantly longer stone recurrence-free period than the high urine concentration group (log-rank test, P < 0.001). In multivariate Cox regression analyses, 24-h UOsm was seen to be an independent risk factor for stone recurrence., Conclusions: UOsm is a promising approach to assessing hydration and predicting stone recurrence in patients with urolithiasis. Maintaining UOsm < 564 mOsm/kg H 2 O may reduce the risk of stone recurrence.

The present study aimed to identify novel methylation markers of clear cell renal cell carcinoma (ccRCC) using microarray methylation analysis and evaluate their prognostic relevance in patient samples. To identify cancer‑specific methylated biomarkers, microarray profiling of ccRCC samples from our institute (n=12) and The Cancer Genome Atlas (TCGA) database (n=160) were utilized, and the prognostic relevance of candidate genes were investigated in another TCGA dataset (n=153). For validation, pyrosequencing analyses with ccRCC samples from our institute (n=164) and another (n=117) were performed and the potential clinical application of selected biomarkers was examined. We identified 22 CpG island loci that were commonly hypermethylated in ccRCC. Kaplan‑Meier analysis of TCGA data indicated that only 4/22 loci were significantly associated with disease progression. In the internal validation set, Kaplan‑Meier analysis revealed that hypermethylation of two loci, zinc finger protein 492 (ZNF492) and G protein‑coupled receptor 149 (GPR149), was significantly associated with shorter time‑to‑progression. Multivariate Cox regression models revealed that hypermethylation of ZNF492 [hazard ratio (HR), 5.44; P=0.001] and GPR149 (HR, 7.07; P<0.001) may be independent predictors of tumor progression. Similarly, the methylation status of these two genes was significantly associated with poor outcomes in the independent external validation cohort. Collectively, the present study proposed that the novel methylation markers ZNF492 and GPR149 could be independent prognostic indicators in patients with ccRCC.

Background: Disease monitoring in non-muscle-invasive bladder cancer (NMIBC) patients is crucial for early identification of disease recurrence and progression. High IQGAP3/BMP4 and IQGAP3/FAM107A ratios in urinary cell-free DNA (ucfDNA) are a diagnostic biomarker for bladder cancer. We aimed to investigate whether the levels of these biomarkers in ucfDNA can be used to monitor disease recurrence or progression in patients with NMIBC., Patients and Methods: A total of 103 patients with NMIBC (pTa-pT1) were enrolled. The IQGAP3/BMP4 and IQGAP3/FAM107A ratios in ucfDNA were measured by real-time PCR, and the results were compared with clinical outcome by Kaplan-Meier curves and Cox regression analyses., Results: Overall, 55 patients (53.4%) experienced recurrence and 29 (28.2%) experienced disease progression during a median follow-up of 42.7 months (range, 6.1-172.2 months). Kaplan-Meier analysis revealed that NMIBC patients with a high IQGAP3/BMP4 ratio had worse recurrence-free survival and progression-free survival (PFS) (P = .001 and < .001, respectively), and those with a high IQGAP3/FAM107A ratio had worse PFS (P = .006). Multivariate Cox regression analysis revealed that the IQGAP3/BMP4 ratio was independently associated with recurrence-free survival (hazard ratio, 2.462; P = .003) and PFS (hazard ratio = 3.871; P = .004), whereas the IQGAP3/FAM107A ratio was not an independent factor for PFS (P = .079)., Conclusion: The IQGAP3/BMP4 ratio in ucfDNA might be a valuable novel biomarker for predicting disease recurrence and progression in patients with NMIBC., (Copyright © 2019. Published by Elsevier Inc.)

Background: Little is known about epigenetic silencing of genes by promoter hypermethylation in renal cell carcinoma (RCC). The aim of this study was to identify prognostic methylation markers in surgically treated clear cell RCC (ccRCC)., Methods: Methylation patterns were assayed using the Infinium HumanMethylation450 BeadChip array on pairs of ccRCC and normal tissue from 12 patients. Using quantitative PSQ analysis, tumor-specific hypermethylated genes were validated in 25 independent cohorts and their clinical relevance was also verified in 152 independent cohorts., Results: Using genome-wide methylation array, Zinc finger protein 278 ( ZNF278 ), Family with sequence similarity 155 member A ( FAM155A ) and Dipeptidyl peptidase 6 ( DPP6 ) were selected for tumor-specific hypermethylated genes in primary ccRCC. The promoter methylation of these genes occurred more frequently in ccRCC than normal kidney in independent validation cohort. The hypermethylation of three genes were associated with advanced tumor stage and high grade tumor in ccRCC. During median follow-up of 39.2 (interquartile range, 15.4-79.1) months, 22 (14.5%) patients experienced distant metastasis. Multivariate analysis identified the methylation status of these three genes, either alone, or in a combined risk score as an independent predictor of distant metastasis., Conclusion: The promoter methylation of ZNF278 , FAM155A and DPP6 genes are associated with aggressive tumor phenotype and early development of distant metastasis in patients with surgically treated ccRCC. These potential methylation markers, either alone, or in combination, could provide novel targets for development of individualized therapeutic and prevention regimens., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2019 The Korean Academy of Medical Sciences.)

Purpose: To analyze trends over a period of 28 years in the clinical, operative, and pathologic characteristics of patients with a renal mass who underwent surgical resection in Korea., Materials and Methods: Consecutive patients (n=6,231) with a renal mass who underwent surgical resection at eight Korean institutions between 1988 and 2015 were reviewed. Patients were assigned to one of three groups according to the date of surgery: group 1, 1988-1999; group 2, 2000-2009; and group 3, 2010-2015., Results: Age at the time of surgery, body mass index, smoking status, incidence of diabetes and hypertension, and the number of incidentally identified renal masses increased significantly over time. The proportion of patients undergoing partial nephrectomy (PN) or minimally invasive surgery (MIS) increased sharply during the last two time periods. From 2010, the rate of robot-assisted nephrectomy rose sharply, occurring in 37.8% of MIS cases. Benign pathology was identified in 1.8% and 5.2% of cases in the middle and last periods, respectively; angiomyolipoma was the most common pathology. In later years, tumors were more often localized, although tumor grade increased. Sub-group analysis of small renal masses ≤4 cm revealed similar trends in operative and pathologic characteristics over time., Conclusions: Between 1988 and 2015, there was a substantial change in the clinical, operative, and histological characteristics of patients who underwent resection of a renal mass in Korea. The most notable changes were stage migration towards localized disease and widespread use of PN and MIS., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Purpose: The prognostic role of the controlling nutritional status (CONUT) score in renal cell carcinoma (RCC) has not been evaluated. The aim of the current study was to clarify the prognostic significance of the CONUT score in Korean patients with surgically treated RCC., Materials and Methods: A database of 1,881 patients with surgically treated RCC from a multiinstitutional Korean collaboration between 1999 and 2015 was analyzed. The preoperative CONUT score was calculated from serum albumin, total cholesterol concentrations, and total lymphocyte count. Clinicopathological variables and survival rates were compared between the CONUT score groups., Results: A high CONUT score was associated with older age, lower body mass index, lower preoperative prognostic nutritional index, and presence of diabetes or hypertension (each P < 0.001). Regarding pathologic features, a high CONUT score was associated with aggressive tumor characteristics including large tumor size, advanced stage, high nuclear grade, lymphovascular invasion, and sarcomatous differentiation (each P < 0.001). Multivariate Cox regression analysis indicated that a high CONUT score (≥ 2) was an independent predictor of cancer-specific mortality (hazard ratio, 1.892; 95% CI: 1.118-3.201; P = 0.018)., Conclusion: The CONUT score, an easily measurable immune-nutritional biomarker, may provide useful prognostic information in patients with surgically treated RCC.

Background: Pathologic T1 high-grade (pT1HG) bladder cancer (BC) is characterized by a high progression rate and constitutes an important clinical challenge; however, there is no consensus on the prediction of progression in pT1HG BC. The purpose of this study was to validate previously published molecular progression risk score (MoPRS) for predicting muscle-invasive disease in pT1HG BC., Materials and Methods: The expression of an 8-gene progression-related classifier identified from microarray data was analyzed by real-time PCR, and the MoPRS was calculated in 121 newly recruited patients with pT1HG BC. Progression was defined as muscle invasion or metastasis., Results: Overall, the disease of 28 patients (23.1%) progressed to muscle-invasive BC during the median follow-up of 63.7 (interquartile range, 17.6-96.4) months. The MoPRS was significantly higher in 1973 World Health Organization grade 3 than grade 2 tumors (P = .004). Early development of invasive BC was more prevalent in the highest quartile MoPRS group than in the lowest to 75th percentile MoPRS groups according to Kaplan-Meier analysis. Multivariate Cox regression analysis revealed that the MoPRS was an independent predictor of invasive BC, either as a continuous variable (hazard ratio, 1.624; 95% confidence interval, 1.266-2.082; P < .001) or as a categorical variable (hazard ratio, 3.089; 95% confidence interval, 1.335-7.150; P = .008)., Conclusion: The MoPRS was an independent prognostic factor for identifying patients at high risk of invasive BC in patients with pT1HG BC. This scale may help identify patients who could benefit from more aggressive therapeutic intervention such as early cystectomy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Differentially expressed genes and their post-transcriptional regulator-microRNAs (miRNAs), are potential keys to pioneering cancer diagnosis and treatment. The aim of this study was to investigate how the miRNA-mRNA interactions might affect the tumorigenesis of bladder cancer (BC) and to identify specific miRNA and mRNA genetic markers in the two BC types: non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC)., Results: We identified 227 genes that interacted with 54 miRNAs in NMIBC, and 14 genes that interacted with 10 miRNAs in MIBC. Based on this data, we found extracellular matrix-related genes are highly enriched in NMIBC while genes related to core nuclear division are highly enriched in MIBC. Furthermore, using a transcriptional regulatory element database, we found indirect regulatory transcription factors (TFs) for enriched genes could regulate tumorigenesis with or without miRNAs., Materials and Methods: Tissue samples from 234 patients histologically diagnosed with BC and 83 individuals without BC were analyzed using microarray and next-generation sequencing technology, and we used different cut-offs to identify differentially expressed mRNAs and miRNAs in NMIBC and MIBC. The selected mRNAs and miRNAs were paired using validated target datasets and according to inverse expression relationships. MiRNA interacted genes were compared with the TF-regulating genes in BC. Meanwhile, pathway enrichment analysis was performed to identify the functions of selected miRNAs and genes., Conclusions: Identification of differential gene expression in specific tumor types could facilitate development of cancer diagnosis and aid in the early detection of BC., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Background: There is growing interest in developing new non-invasive diagnostic tools for bladder cancer (BC) that have better sensitivity and specificity than cystoscopy and cytology. This study examined the value of urinary cell-free nucleic acid (NA) as a diagnostic marker for BC., Material and Methods: A total of 81 patients (74 BC and 7 normal controls) were used for a tissue set, and 212 patients (92 BC and 120 normal controls) were used as a urine set. Expression of tissue mRNA and urinary cell-free NAs was then examined., Results: Four candidate genes were top-ranked in the tissue microarray. Expression levels of two of these (IQGAP3 and TOP2A) in BC tissue and urine samples from BC patients were significantly higher than those in samples from the control groups. Binary logistic regression analysis of cell-free NA levels in urine samples revealed that IQGAP3 was significantly associated with BC: PicoGreen-adjusted odds ratio (OR), 3.434; confidence interval (CI), 2.999-4.180; P <0.001; RiboGreen-adjusted OR, 2.242; CI, 1.793-2.840; P <0.001. Further analysis of IQGAP3 urinary cell-free NAs with respect to tumor invasiveness and grade also yielded a high AUC, suggesting that IQGAP3 can discriminate between BC patients and non-cancer patients with hematuria., Conclusions: Levels of IQGAP3 urinary cell-free NA in BC patients were significantly higher than those in normal controls or patients with hematuria. High levels of IQGAP3 urinary cell-free NA also reflected high expression in BC tissues. Therefore, IQGAP3 urinary cell-free NA may be a complementary diagnostic biomarker for BC., Competing Interests: CONFLICTS OF INTEREST The authors have no conflicts of interest to declare.

Background: The prognostic implications of preoperative serum total cholesterol (TC) level in patients with renal cell carcinoma (RCC) remain poorly understood. We investigated the prognostic role of preoperative serum TC in patients with surgically treated RCC from a large, multi-institutional Korean collaboration., Patients and Methods: A database of 3064 patients with RCC who underwent radical or partial nephrectomy between 1999 and 2011 at eight academic centers was analyzed. Preoperative serum TC levels were measured in fasting blood samples., Results: Low preoperative serum TC level was associated with aggressive tumor characteristics, including large tumor size, advanced stage, high nuclear grade, lymph node involvement, and sarcomatous differentiation (all P < 0.001). Low TC level was associated with poor recurrence-free or cancer-specific survival (CSS) in the entire cohort, whereas the significance of the association changed after stratification by disease stage and histologic subtype. Multivariate Cox regression analysis showed that preoperative TC, as a continuous or categorical variable, was an independent predictor of CSS., Conclusions: Preoperative low serum TC level was associated with aggressive tumor characteristics and poor CSS in patients with surgically treated RCC. Preoperative TC may provide additional guidance regarding the choice of therapeutic strategies to improve prognosis.

Although garlic induces apoptosis in cancer cells, it is unclear whether the effects are similar to those of cisplatin against bladder cancer (BC). Therefore, this study investigated whether garlic extracts and cisplatin show similar activity when used to treat BC. The effect of garlic on T24 BC cell line was examined in a BALB/C-nude mouse xenograft model and compared with that of cisplatin. Tissue microarray analysis and gene network analysis were performed to identify differences in gene expression by control tumors and tumors exposed to garlic extract or cisplatin. Investigation of gene expression based on tissues from 165 BC patients and normal controls was then performed to identify common targets of garlic and cisplatin. Tumor volume and tumor weight in cisplatin (0.05[Formula: see text]mg/kg)- and garlic-treated mice were significantly smaller than those in negative control mice. However, cisplatin-treated mice also showed a significant reduction in body weight. Microarray analysis of tumor tissue identified 515 common anticancer genes in the garlic and cisplatin groups ([Formula: see text]). Gene network analysis of 252 of these genes using the Cytoscape and ClueGo software packages mapped 17 genes and 9 gene ontologies to gene networks. BC (NMIBC and MIBC) patients with low expression of centromere protein M (CENPM) showed significantly better progression-free survival than those with high expression. Garlic extract shows anticancer activity in vivo similar to that of cisplatin, with no evident of side effects. Both appear to act by targeting protein-DNA complex assembly; in particular, expression of CENPM.

Purpose: In this retrospective cohort study we assessed the effect on prostate specific antigen concentration of low dose finasteride or dutasteride treatment for male androgenetic alopecia in men with baseline serum prostate specific antigen less than 2.5 ng/ml., Materials and Methods: The cohort consisted of 1,379 consecutive male patients who were treated for androgenetic alopecia with finasteride 1.25 mg daily or dutasteride 0.5 mg every 3 days in 2002 to 2012 and who underwent prostate specific antigen measurements at baseline and at least once thereafter. Patients in whom baseline or followup prostate specific antigen after prescription exceeded 2.5 ng/ml were excluded from study to rule out men with a higher likelihood of prostate cancer. Patients were stratified according to age, baseline prostate specific antigen, medication type and treatment duration., Results: Overall low dose 5α-reductase inhibitor treatment reduced prostate specific antigen by 27.8% relative to baseline. Of the patients 1,094 (79.3%) showed prostate specific antigen decreases (average 40.8%). In the remaining 285 patients (20.7%) prostate specific antigen was stable or increased (average 24.2% increase). Closer analysis largely showed that only men with baseline prostate specific antigen 0.5 ng/ml or greater had a treatment related prostate specific antigen reduction. On multivariate logistic analysis low baseline prostate specific antigen was significantly associated with stable/increased prostate specific antigen. Low dose dutasteride and finasteride reduced prostate specific antigen to similar degrees (31.1% and 25.1%, respectively). A marked prostate specific antigen decrease of 26.0% was observed even after short-term treatment (3 to 6 months)., Conclusions: Dutasteride and finasteride reduced prostate specific antigen to similar degrees. This effect was observed soon after commencing treatment. In patients with low baseline prostate specific antigen the levels could remain stable or even increase. These findings are limited to men with baseline prostate specific antigen less than 2.5 ng/ml., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Urolithiasis is common and is becoming more prevalent worldwide. This study assessed the chronological trends in clinical and urinary metabolic features over 20 years in Korean urolithiasis patients. We performed a retrospective analysis of 4,076 patients treated at our clinic from 1996 to 2015. Urinary metabolic data and stone analysis data were available for 1,421 and 723 patients (34.9% and 17.7%), respectively. Patients were categorized into 4 groups according to the date of initial diagnosis: group 1 (1996-2000, n = 897), group 2 (2001-2005, n = 1,018), group 3 (2006-2010, n = 1,043), and group 4 (2011-2015, n = 1,118). Incidental detection of uric acid renal stones has become more prevalent in the past 10 years, accompanied by an increase in body mass index and age at diagnosis. Similarly, the prevalence of diabetes mellitus and of hypertension increased from one group to the next throughout the study period. Levels of 24-hour urinary excretion of sodium, calcium, uric acid, and oxalate have decreased significantly over the study period. The incidence of urinary metabolic abnormalities also showed an identical tendency. The proportion of stones composed of uric acid increased over the study period. In conclusion, incidental detection of uric acid renal stones has become more prevalent in Korea in the past 20 years. Urinary excretion of lithogenic constituents and the incidence of urinary metabolic abnormalities have decreased significantly over this period., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2017 The Korean Academy of Medical Sciences.)

Our previous study reported a clinically applicable prognostic gene classifier for primary non-muscle-invasive bladder cancer (NMIBC). The present study aimed to perform long-term validation of this classifier in the prediction of muscle-invasive disease. Previously published gene expression profiles were used from 176 patients with NMIBC with extended follow-up. Progression was defined as development of muscle invasion or metastasis, and the progression risk score was calculated using the previously developed eight-gene progression classifier. During median follow-up of 72.8 (interquartile range, 37.0-118.7) months, 26 (14.8%) patients progressed to muscle-invasive bladder cancer. The molecular progression risk score was significantly associated with clinicopathological variables, including tumor number, stage, grade and multivariate risk assessment tools (P<0.05 in each case). Multivariate Cox regression analysis revealed that molecular progression risk score was an independent predictor of development of invasive tumor, either as a continuous variable [hazard ratio (HR), 1.489; 95% confidence interval (CI), 1.216-1.823; P<0.001] or as a categorical variable (HR, 5.026; 95% CI, 1.619-15.608; P=0.005). In conclusion, the present results confirmed the clinical utility of the progression-associated gene classifier for prediction of development of muscle invasion in NMIBC. The molecular progression risk score may aid in selecting patients who could benefit from more aggressive therapeutic intervention.

Purpose: The aim of this study was to assess the metabolic characteristics and risks of stone recurrence in young adult stone patients in Korea., Patients and Methods: The medical records of 1532 patients presenting with renal or ureteric stones at our stone clinic between 1994 and 2015 were retrospectively reviewed. Patients were grouped according to age (young adult, 18-29 years; intermediate onset, 30-59 years; old age, ≥60 years) at first presentation, and measurements of clinicometabolic characteristics and risks of stone recurrence were compared., Results: Overall, excretion of urinary stone-forming substances was highest in the intermediate onset group, followed by the young adult and old age groups. Importantly, excretion of urinary citrate was lowest in the young adult group. Kaplan-Meier analyses identified a significant difference between the three age groups in terms of stone recurrence (log rank test, p < 0.001). Multivariate Cox regression analyses revealed that age at first stone presentation was an independent risk factor for stone recurrence. Urinary citrate excretion was an independent risk factor for stone recurrence in young adult stone patients., Conclusions: Younger age (18-29 years) at first stone presentation was a significant risk factor for stone recurrence, and urinary citrate excretion was an independent risk factor affecting recurrence in this group. Metabolic evaluation and potassium citrate therapy should be considered for young adult stone patients to prevent recurrence.

There is a growing interest in the use of naturally occurring agents in cancer prevention. This study investigated the garlic extract affects in bladder cancer (BC) prevention. The effect of garlic extract in cancer prevention was evaluated using the T24 BC BALB/C-nude mouse xenograft model. Microarray analysis of tissues was performed to identify differences in gene expression between garlic extract intake and control diet, and gene network analysis was performed to assess candidate mechanisms of action. Furthermore, we investigated the expression value of selected genes in the data of 165 BC patients. Compared to the control group, significant differences in tumor volume and tumor weight were observed in the groups fed 20 mg/kg (p<0.05), 200 mg/kg, and 1000 mg/kg of garlic extract (p<0.01). Genes (645) were identified as cancer prevention-related genes (fold change >2 and p<0.05) by tissue microarray analysis. A gene network analysis of 279 of these genes (p<0.01) was performed using Cytoscape/ClueGo software: 36 genes and 37 gene ontologies were mapped to gene networks. Protein kinase A (PKA) signaling pathway including AKAP12, RDX, and RAB13 genes were identified as potential mechanisms for the activity of garlic extract in cancer prevention. In BC patients, AKAP12 and RDX were decreased but, RAB13 was increased. Oral garlic extract has strong cancer prevention activity in vivo and an acceptable safety profile. PKA signaling process, especially increasing AKAP12 and RDX and decreasing RAB13, are candidate pathways that may mediate this prevention effect.

The aim of the present multi-institutional study was to assess the influence of the American Society of Anesthesiologists Physical Status (ASA-PS) classification on adjuvant chemotherapy eligibility and survival in a multi-institutional cohort of patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). We retrospectively reviewed data from 416 patients who underwent RNU for UTUC at four Korean institutions between 2001 and 2013. The ASA-PS classification was obtained from the anesthesia chart. Locally advanced UTUC was defined as ≥ pT3 and/or pN1 disease. The influence of ASA-PS score on survival was evaluated by Kaplan-Meier analyses and a multivariate Cox regression model. Patients with a higher ASA-PS class were less likely to be eligible for adjuvant chemotherapy in locally advanced UTUC (P = 0.016). Kaplan-Meier estimates showed that the high-risk ASA-PS group has a poorer overallsurvival (OS) and cancer-specific survival (CSS) compared to low risk ASA-PS groups in both the total and locally advanced UTUC cohorts. Based on multivariate Cox regression analysis, the high-risk ASA-PS category was an independent predictor for overall mortality (OM) (hazard ratio [HR], 1.919; 95% confidence interval [CI], 1.017-3.619; P = 0.044) and cancer-specific mortality (CSM) (HR, 2.120; 95% CI, 1.023-4.394; P = 0.043). In conclusion, high-risk ASA-PS score was independently associated with a lower survival rate in patients with UTUC after RNU. However, the influence of ASA-PS classification on survival was limited to locally advanced UTUC. The lower eligibility of patients in the high-risk ASA category for adjuvant chemotherapy may contribute to the lower survival rate in this group., Competing Interests: The authors have no potential conflicts of interest to disclose.

The prognostic significance of age in renal cell carcinoma (RCC) is a subject of debate. The aim of the present multi-institutional study was to evaluate the impact of age on clinicopathological features and survival in a large cohort of patients with RCC. A total of 5,178 patients who underwent surgery for RCC at eight institutions in Korea between 1999 and 2011 were categorized into three groups according to age at diagnosis as follows: young age (< 40 years, n = 541), middle-age (≥ 40 and < 60 years, n = 2,551), and old age (≥ 60 years, n = 2,096) groups. Clinicopathological variables and survival rates were compared between the three groups. Young patients had lower stage tumors with a low Fuhrman grade, a lower rate of lymphovascular invasion than patients in the other age groups. Regarding histologic type, the young age group had a lower percentage of clear cell histology and a greater incidence of Xp11.2 translocation RCC. Kaplan-Meier estimates showed that cancer-specific survival was significantly better in the young age group than in the other groups (log rank test, P = 0.008). However, age at diagnosis was not an independent predictor of survival in multivariate analysis. In conclusion, young age at diagnosis was associated with favorable pathologic features, although it was not an independent prognostic factor for survival in patients with surgically-treated RCC. Age itself should not be regarded as a crucial determinant for the treatment of RCC., Competing Interests: The authors have no potential conflicts of interest to disclose.

The potential use of urinary nucleic acids as diagnostic markers in prostate cancer (PCa) was evaluated. Ninety-five urine samples and 234 prostate tissue samples from patients with PCa and benign prostatic hyperplasia (BPH) were analyzed. Micro-array analysis was used to identify candidate genes, which were verified by the two-gene expression ratio and validated in tissue mRNA and urinary nucleic acid cohorts. Real-time quantitative polymerase chain reaction (qPCR) was used to measure urinary nucleic acid levels and tissue mRNA expression. The TSPAN13-to-S100A9 ratio was selected to determine the diagnostic value of urinary nucleic acids in PCa (P = 0.037) and shown to be significantly higher in PCa than in BPH in the mRNA and nucleic acid cohort analyses (P < 0.001 and P = 0.013, respectively). Receiver operating characteristic (ROC) analysis showed that the area under the ROC curve was 0.898 and 0.676 in tissue mRNA cohort and urinary nucleic acid cohort, respectively. The TSPAN13-to-S100A9 ratio showed a strong potential as a diagnostic marker for PCa. The present results suggest that the analysis of urine supernatant can be used as a simple diagnostic method for PCa that can be adapted to the clinical setting in the future.

Previous studies have shown that c-MET is overexpressed in cases of aggressive bladder cancer (BCa). Identification of crosstalk between c-MET and other RTKs such as AXL and PDGFR suggest that c-MET network genes (c-MET-AXL-PDGFR) may be clinically relevant to BCa. Here, we examine whether expression of c-MET network genes can be used to identify BCa patients at increased risk of developing aggressive disease. In vitro analysis, c-MET knockdown suppressed cell proliferation, invasion, and migration, and increased sensitivity to cisplatin-induced apoptosis. In addition, c-MET network gene (c-MET, AXL, and PDGFR) expression allowed discrimination of BCa tissues from normal control tissues and appeared to predict poor disease progression in non-muscle invasive BCa patients and poor overall survival in muscle invasive BCa patients. These results suggest that c-MET network gene expression is a novel prognostic marker for predicting which BCa patients have an increased risk of developing aggressive disease. These genes might be a useful marker for co-targeting therapy, and are expected to play an important role in improving both response to treatment and survival of BCa patients.

DNA methylation is the most common and well-characterized epigenetic change in human cancer. Recently, an association between prostate cancer susceptibility candidate (PRAC) methylation and genitourinary cancer was proposed. The aim of the present study was to evaluate the association between PRAC methylation status and clinicopathological parameters and prognosis in long-term follow-up primary nonmuscle invasive bladder cancer (NMIBC). The clinical relevance of PRAC methylation was determined in 136 human bladder specimens (eight normal controls [NCs] and 128 primary NMIBCs) using quantitative pyrosequencing analysis. PRAC methylation was significantly higher in NMIBC patients than in NCs and was significantly associated with higher grade and more advanced stage of cancer. Kaplan-Meier estimates revealed significant difference in tumor recurrence and progression according to PRAC methylation status (both p < 0.05). Multivariate Cox regression analysis revealed that the PRAC methylation status was a strong predictor of recurrence (hazard ratio [HR], 2.652; p = 0.012) and progression (HR, 9.531; p = 0.035) of NMIBC. Enhanced methylation status of PRAC was positively associated with a high rate of recurrence and progression in NMIBC patients, suggesting that PRAC methylation may be a promising prognostic marker of NMIBC.

Objective: To assess the influence of dyslipidemia on urinary lithogenic metabolites and stone recurrence in stone formers., Materials and Methods: We retrospectively selected 321 patients with urolithiasis who had been followed up for >24 months between 2004 and 2009. Fasting blood samples were taken, and serum lipid profiles were measured. All subjects also underwent 24-hour urinary metabolic evaluation and stone analysis. The radiographic appearance of new stones was defined as stone recurrence., Results: There was no significant correlation between lipid profiles and 24-hour urine metabolites (all P >.05). Stone formers with hypertriglyceridemia had significantly higher urinary calcium, sodium, uric acid, magnesium, and potassium excretions. Only in a subgroup of uric acid stone, hypertriglyceridemia was significantly associated with decreased urinary pH. Those with low high-density lipoprotein (HDL) cholesterolemia had higher urinary sodium, magnesium, and potassium excretions, whereas those with high low-density lipoprotein (LDL) cholesterolemia had lower urinary sodium excretion. Stone analysis revealed that uric acid stones were more commonly found in patients with hypertriglyceridemia and low-HDL cholesterolemia. After a median follow-up of 35.0 months, 109 patients (34% of cohort) had stone recurrence. Stone recurrence was more common in the hypertriglyceridemia group compared with the normal triglyceridemia group (45.9% vs 29.7%; P = .005). The multivariate Cox regression model revealed that hypertriglyceridemia is associated independently with stone recurrence (hazard ratio, 1.857; 95% confidence interval, 1.211-2.847; P = .005). Kaplan-Meier curves showed similar results., Conclusion: Our study showed that serum lipid profile is associated with urine metabolic alterations. More importantly, hypertriglyceridemia is independently associated with increased risk for stone recurrence in patients with urolithiasis., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The study was designed to assess the relationship between glomerular filtration rate (GFR) and urinary stone-forming constituents, and to assess the effect of renal insufficiency on stone recurrence risk in first stone formers (SF). Baseline serum creatinine levels were obtained, and renal insufficiency was defined as creatinine clearance ≤60 mL/min (Cockroft-Gault). This retrospective case-control study consists of 342 first SF; 171 SF with normal renal function were selected with 1:1 propensity scores matched to 171 SF with renal insufficiency. Urinary metabolic evaluation was compared to renal function. GFR was positively correlated with urinary calcium, uric acid, and citrate excretion. Subjects with renal insufficiency had significantly lower urinary calcium, uric acid, and citrate excretion than those with normal renal function, but not urine volume. With regard to urinary metabolic abnormalities, similar results were obtained. SF with renal insufficiency had lower calcium oxalate supersaturation indexes and stone recurrence rates than SF with normal renal function. Kaplan-Meier curves showed similar results. In conclusion, GFR correlates positively with urinary excretion of stone-forming constituents in SF. This finding implies that renal insufficiency is not a risk factor for stone recurrence.

Objective: To characterize the clinical and metabolic abnormalities of patients presenting with multiple stones and determine their risk of new stone formation., Materials and Methods: This retrospective case-controlled study consisted of 911 patients who had ureter stones for the first time and 107 age- and sex-matched patients without stones. The patients were classified into 2 groups: those with a single ureter stone (n = 690) and those with 1 or more additional stones somewhere in the ureter or kidney (n = 221). All patients underwent 24-hour urinary metabolic evaluation. The 240 patients (26.3%) who were followed for >12 months (median follow-up, 35.0 months) were included in recurrence analyses. Stone recurrence was defined as "new stone formation," namely, the radiographic appearance of stones that had not been present in previous examinations., Results: The multiple-stone group had significantly lower urinary citrate excretion than the single-stone (P = .011) and control (P = .003) groups. Compared with the single-stone group, it also had a higher incidence of hypocitraturia (P = .011) and stone recurrence (27 of 84 [32.1%] vs 29 of 156 [18.6%] patients; P = .025). Multivariate Cox regression analyses revealed that stone multiplicity (hazard ratio, 2.343; 95% confidence interval, 1.302-4.220; P = .005) was an independent predictor of recurrent stone formation. Kaplan-Meier curves showed identical results., Conclusion: The patients with multiple stones had distinct metabolic characteristics, particularly hypocitraturia and a significantly higher risk of recurrence than patients with 1 stone. Patients with multiple stones, even if it is their first stone episode, should undergo metabolic evaluation and possibly also potassium citrate therapy to prevent future stones., (Copyright © 2014 Elsevier Inc. All rights reserved.)