Sung Pil Seo

Hypertriglyceridemia is associated with increased risk for stone recurrence in patients with urolithiasis.

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.

Clinical Implications and Prognostic Values of Prostate Cancer Susceptibility Candidate Methylation in Primary Nonmuscle Invasive Bladder Cancer

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.

Long-term validation of a molecular progression-associated gene classifier for prediction of muscle invasion in primary non-muscle-invasive bladder cancer

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.

Impact of the ASA Physical Status Score on Adjuvant Chemotherapy Eligibility and Survival of Upper Tract Urothelial Carcinoma Patients: a Multicenter Study

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.

Impact of Young Age at Diagnosis on Survival in Patients with Surgically Treated Renal Cell Carcinoma: a Multicenter Study

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.

Change in Prostate Specific Antigen Concentration in Men with Prostate Specific Antigen Less than 2.5 ng/ml Taking Low Dose Finasteride or Dutasteride for Male Androgenetic Alopecia

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 5&agr;‐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.

Prognostic Impact of Nutritional Status Assessed by the Controlling Nutritional Status (CONUT) Score in Patients with Surgically Treated Renal Cell Carcinoma

Abstract 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.

Molecular Progression Risk Score for Prediction of Muscle Invasion in Primary T1 High-Grade Bladder Cancer

Micro‐Abstract The present study identified the molecular progression risk score (MoPRS) as an independent prognostic factor for identifying patients at high risk of invasive bladder cancer (BC) in patients with pathologic T1 high‐grade BC (pT1HG BC). The MoPRS could be applied to improve clinical decision‐making and for counseling patients with pT1HG BC. 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.

MP65-14 LONG-TERM VALIDATION OF A MOLECULAR PROGRESSION–RELATED GENE CLASSIFIER FOR PREDICTION OF MUSCLE INVASION IN PRIMARY NON–MUSCLE-INVASIVE BLADDER CANCER

INTRODUCTION AND OBJECTIVES: Previously, we reported a clinically applicable prognostic gene classifier for primary non-muscleinvasive bladder cancer (NMIBC). In the present study, we sought to perform long-term validation of this classifier in the prediction of muscleinvasive disease. METHODS: We used previously published gene expression profiles from 176 NMIBC patients 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. RESULTS: 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, 1.489; 95% CI, 1.216-1.823; P < 0.001) or as a categorical variable (hazard ratio, 5.026; 95% CI, 1.619-15.608; P 1⁄4 0.005). CONCLUSIONS: Our results confirm the clinical utility of the progression-related gene classifier for prediction of development of muscle invasion in NMIBC. The molecular progression risk score could aid in selecting patients who could benefit from more aggressive therapeutic intervention.

Chronological Trends in Clinical and Urinary Metabolic Features over 20 Years in Korean Urolithiasis Patients

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.