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PurposeMelanoma incidence is rising worldwide along with the associated personal and socioeconomic health expenditures. We investigated the incidence and survival-rate patterns of melanoma in South Korea using nationwide data. Materials and MethodsThis retrospective cohort study included patients with melanoma between 2004 and 2017, based on National Health Insurance (NHI) claims data in South Korea. The incidence, prevalence, and survival rate were analyzed along with baseline demographic characteristics. We collected solar irradiation dose (SID) and healthcare ranking score (HRS) according to the administrative district from the Korea Meteorological Administration and Korea Health Promotion Institute. The incidence and survival rates were assessed using Pearson's correlation, the Kaplan-Meier estimation, multiple linear regression, and multiple logistic regression methods.ResultsTwenty-five thousand, five hundred ninety-one patients with melanoma were diagnosed during the study period. The age-standardized incidence of melanoma steadily increased from 2004 to 2017 from 2.6 to 3.0/100,000/yr. The incidence of melanoma increased with significantly higher income (p < 0.05). The prevalence followed a similar pattern as the incidence. According to multivariate analysis, HRS significantly influenced the incidence of melanoma in high sun-exposed sites (p < 0.001). There was no significant change in annual mortality. Women had a higher 5-year survival rate than men (78.4% vs. 72.8%). Mortality by the administrative district was highly correlated with HRS.ConclusionThe incidence of melanoma is increasing in South Korea. A low HRS is associated with both higher incidence and mortality. The findings of this study could be utilized as a guideline for treating melanoma patients.

Background The efficacy of modified FOLFIRINOX (mFOLFIRINOX) as a second-line chemotherapy treatment for metastatic pancreatic adenocarcinoma (mPAC), remains unclear. This multi-center randomised phase III trial aimed to elucidate the efficacy of mFOLFIRINOX as a second-line chemotherapy treatment for mPAC patients with good performance status. Patients and methods Eighty mPAC patients (age, 19–75 years) refractory to first-line gemcitabine-based chemotherapy were randomly selected to receive mFOLFIRINOX or S-1. mFOLFIRINOX comprised oxaliplatin (65 mg/m2), irinotecan (135 mg/m2), and leucovorin (400 mg/m2) on day 1 and continuous 5-FU infusion (1000 mg/m2) over 24 h on days 1–2 every 2 weeks. S-1 comprised body surface area-dependent oral S-1, divided into two doses per day on days 1–28 every 6 weeks. Results Overall survival was the primary endpoint. The objective response and disease control rates were higher in the mFOLFIRINOX than in the S-1 group (15% versus 2%; p = .04 and 67% versus 37%; p = .007). The median progression-free survival rates were 5.2 and 2.2 months in the mFOLFIRINOX and S-1 groups, respectively (adjusted hazard ratio [HR]: .4; 95% confidence interval [CI]: .2-.6; p Conclusion Administration of mFOLFIRINOX as a second-line chemotherapy treatment for mPAC patients refractory to gemcitabine-based chemotherapy resulted in increased survival rates than S-1 treatment alone.

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 (, Graphical Abstract

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). 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. 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. 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.

No study has evaluated the prognostic impact of the age-adjusted Charlson comorbidity index (AACI) in those with renal cell carcinoma (RCC). This study aimed to evaluate the utility of the AACI for predicting long-term survival in patients with surgically treated non-metastatic clear cell RCC (ccRCC). Data from 698 patients with non-metastatic ccRCC who underwent radical or partial nephrectomy as primary therapy from a multi-institutional Korean collaboration between 1988 and 2015 were retrospectively analyzed. Clinicopathological variables and survival outcomes of those with AACI scores ≤ 3 (n = 324), 4–5 (n = 292), and ≥ 6 (n = 82) were compared. Patients with a high AACI score were older and more likely to be female. They were also more likely to have diabetes or hypertension, a worse Eastern Cooperative Oncology Group performance status, and lower preoperative hemoglobin, albumin, serum calcium, and serum total cholesterol levels. Regarding pathologic features, a high AACI score was associated with advanced stage. Kaplan–Meier analyses revealed that AACI ≥ 6 was associated with shorter cancer-specific (log-rank test, P

ObjectiveThe hypertrophic cardiomyopathy (HCM) risk-sudden cardiac death (SCD) calculator endorsed by the 2014 European Society of Cardiology has not been independently validated in the Asians. We aimed to investigate whether the HCM Risk-SCD calculator effectively predicts SCD in Korean HCM population.MethodsAn observational, longitudinal cohort study was performed in 730 patients with HCM from 2007 to 2017. The primary endpoint was a composite of SCD and appropriate implantable cardioverter-defibrillator (ICD) therapy.ResultsDuring a follow-up period of 4288 person-years, 16 (2.2%) patients reached the primary endpoint. This validation study revealed a calibration slope of 0.892 and C-statistics of 0.718. The primary endpoint occurred in 1.1% (7/615), 4.6% (3/65) and 12.0% (6/50) of low-risk, intermediate-risk and high-risk groups, respectively. Although most patients (85.2%) without the primary endpoint were classified into the low-risk group, 7 of 11 SCD (63.6%) occurred in the low-risk group. In univariable and multivariable analysis, sex (woman) was significantly associated with the primary endpoint and emerged as independent predictor. The addition of sex to the HCM Risk-SCD calculator significantly improved the predictive value of the primary endpoint (net reclassification improvement 0.557, p=0.015).ConclusionsIn the Korean HCM population, the HCM Risk-SCD calculator had a high negative predictive value and accuracy for predicting SCD or appropriate ICD therapy, but misclassified a few patients experiencing the primary endpoint as low-risk or intermediate-risk groups.

Purpose A cross-sectional survey was conducted to explore the current awareness and use of complementary and alternative medicine (CAM), as well as attitudes toward CAM, in patients with cancer and their family members in South Korea. Materials and methods Between September 21 and October 31, 2017, a 25-item questionnaire regarding CAM experiences among cancer patients and their family members was conducted in 10 oncology clinics in South Korea after institutional review board approval at each institution. Results In total, 283/310 patients were analyzed. The median age was 60 years, and 60% were male. Most of the patients were actively receiving anticancer treatment at the time of the survey. A total of 106 patients (37%) had experienced a median of two types (interquartile range, 1 to 3) of CAM. Belief in CAM (odds ratio [OR], 3.015; 95% confidence interval [CI], 1.611 to 5.640) and duration of disease (OR, 1.012; 95% CI, 1.004 to 1.020) were independent factors for using CAM in multivariable analysis. Belief in CAM was significantly associated with current use of CAM (OR, 3.633; 95% CI, 1.567 to 8.424). Lay referral was the most common reason for deciding to use CAM, and only 25% of patients (72/283) discussed CAM with their physicians. Conclusion Patient attitudes toward and confidence in CAM modalities were strongly associated with their CAM experiences, and only a small number of patients had an open discussion about CAM with their physicians. A patient education program for CAM is needed.

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 ...

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. 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 H2O, high > 564 mOsm/kg H2O). Metabolic parameters and risk of stone recurrence were compared between the two groups. 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

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.

Numerous biomarkers and risk tables can be used to predict recurrence or progression of patients with primary or recurrent non-muscle invasive bladder cancer (NMIBC) receiving Bacillus Calmette-Guerin (BCG). However, few are suitable for BCG-unresponsive disease (i.e., recurrence or progression after BCG treatment). Therefore, identification of a novel marker that allows accurate prediction of prognosis, particularly risk of recurrence, is critically important in clinical practice. In the current study, gene ontology and gene set enrichment analyses of microarray datasets (GSE13507, n = 47) revealed that differentially expressed genes in recurred NMIBC patients after BCG treatment were associated with virus and ribosomal pathways. Among the core-enrichment genes, the expression of RPL9, a putative tumor suppressor, was lower in recurred NMIBC patients after BCG therapy than in patients without recurrence (P = 0.033) from the E-MTAT-4321 European cohort (n = 84). Data from The Cancer Genome Atlas (n = 406) showed that bladder cancer patients with higher RPL9 expression had a longer overall survival probability than patients with lower RPL9 expression (P = 0.011). Moreover, we used the latest digital PCR platform to examine 59 NMIBC patients and identified downregulation of RPL9 in patients with recurrence after BCG therapy (P = 0.031). The Kaplan-Meier survival estimator showed that NMIBC patients with higher expression of RPL9 had longer recurrence-free survival (log-rank test, P = 0.015). Therefore, we conclude that RPL9 expression is a prospective predictor of recurrence after BCG therapy in NMIBC patients.

Background/Aims Colorectal cancer is associated with different anatomical, biological, and clinical characteristics. We determined the impact of the primary tumor location in patients with metastatic colorectal cancer (mCRC). Methods Demographic data and clinical information were collected from 1,115 patients from the Republic of Korea, who presented with mCRC between January 2009 and December 2011, using web-based electronic case report forms. Associations between the primary tumor location and the patient’s clinical characteristics were assessed, and factors inf luencing overall survival were analyzed using Cox proportional hazards regression models. Results Of the 1,115 patients recruited to the study, 244 (21.9%) had right colon cancer, 483 (43.3%) had left colon cancer, and 388 (34.8%) had rectal cancer. Liver and lung metastases occurred more frequently in patients with left colon and rectal cancer (p = 0.005 and p = 0.006, respectively), while peritoneal and ovarian metastases occurred more frequently in patients with right and left colon cancer (p < 0.001 and p = 0.031, respectively). The median overall survival of patients with tumors originating in the right colon was significantly shorter than that of patients whose tumors had originated in the left colon or rectum (13.7 months [95% confidence interval (CI), 12.0 to 15.5] vs. 18.0 months [95% CI, 16.3 to 19.7] or 19.9 months [95% CI, 18.5 to 21.3], respectively; p = 0.003). Tumor resection, the number of metastatic sites, and primary tumor location correlated with overall survival in the univariate and multivariate analyses. Conclusions Primary tumor location influences the metastatic sites and prognosis of patients with mCRC.

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.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.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).The CONUT score, an easily measurable immune-nutritional biomarker, may provide useful prognostic information in patients with surgically treated RCC.

Purpose Data on the efficacy of olanzapine in patients receiving moderately emetogenic chemotherapy (MEC) are limited. This study aimed to evaluate and compare the efficacy of olanzapine versus placebo in controlling nausea and vomiting in patients receiving MEC. Materials and methods We conducted a randomized, double-blind, placebo-controlled study to determine whether olanzapine can reduce the frequency of chemotherapy-induced nausea and vomiting (CINV) and improve the quality of life (QOL) in patients receiving palonosetron and dexamethasone as prophylaxis for MEC-induced nausea and vomiting. The primary end point was complete response for the acute phase (0-24 hours after chemotherapy). The secondary end points were complete response for the delayed (24-120 hours) and overall phase (0-120 hours), proportion of significant nausea (visual analogue scale ≥ 25 mm), use ofrescue medications, and effect on QOL. Results Fifty-six patients were randomized to the olanzapine (n=29) and placebo (n=27) groups. Complete response rates were not significantly different between the olanzapine and placebo groups in the acute (96.5% vs. 88.0%, p=0.326), delayed (69.0% vs. 48.0%, p=0.118), and overall phases (69.0% vs. 48.0%, p=0.118). However, the percentage of patients with significant nausea (17.2% vs. 44.0%, p=0.032) and the use of rescue medications (0.03±0.19 vs. 1.88±2.88, p=0.002) were lower in the olanzapine group than in the placebo. Furthermore, the olanzapine group demonstrated better QOL (p=0.015). Conclusion Olanzapine combined with palonosetron and dexamethasone significantly improved QOL and vomiting control among previously untreated patients receiving MEC, although the efficacy was limited to the reduction of the frequency of CINV.

Non-muscle-invasive bladder cancer (NMIBC) is a common disease with a high recurrence rate requiring lifetime surveillance. Although NMIBC is not life-threatening, it can progress to muscle-invasive bladder cancer (MIBC), a lethal form of the disease. The management of the two diseases differs, and patients with MIBC require aggressive treatments such as chemotherapy and radical cystectomy. NMIBC patients at a high risk of progression benefit from early immediate cystectomy. Thus, identifying concordant markers for accurate risk stratification is critical to predict the prognosis of NMIBC. Candidate genetic biomarkers associated with NMIBC prognosis were screened by RNA-sequencing of 24 tissue samples, including 16 NMIBC and eight normal controls, and by microarray analysis (GSE13507). Lastly, we selected and investigated a mitotic checkpoint serine/threonine kinase, BUB1, that regulates chromosome segregation during the cell cycle. BUB1 gene expression was tested in 86 NMIBC samples and 15 controls by real-time qPCR. The performance of BUB1 as a prognostic biomarker for NMIBC was validated in the internal Chungbuk cohort (GSE13507) and the external UROMOL cohort (E-MTAB-4321). BUB1 expression was higher in NMIBC patients than in normal controls (p < 0.05), and the overexpression of BUB1 was correlated with NMIBC progression (log-rank test, p = 0.007). In in vitro analyses, BUB1 promoted the proliferation of bladder cancer cells by accelerating the G2/M transition of the cell cycle. Conclusively, BUB1 modulates the G2/M transition to promote the proliferation of bladder cancer cells, suggesting that it could serve as a prognostic marker in NMIBC.

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. 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. 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

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., Graphical Abstract

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

Background The efficacy of epidermal growth factor (EGF) receptor (EGFR) inhibitors in patients with non‐small cell lung cancer (NSCLC), pancreatic cancer (PC), or colorectal cancer (CRC) has been demonstrated. However, dermatological reactions to these inhibitors can cause significant physical and psychosocial discomfort. The objective of the present study was to evaluate the efficacy of EGF ointment for EGFR inhibitor‐related skin adverse events (ERSEs). Materials and Methods This placebo‐controlled, double‐blind, multicenter, pilot phase III trial enrolled patients with NSCLC, PC, or CRC treated with EGFR inhibitors. Patients with grade ≥2 ERSEs were included. Patients were randomized to three treatment arms: arm 1, placebo; arm 2, 1 ppm of EGF ointment; and arm 3, 20 ppm of EGF ointment. Patients applied ointment to their skin lesions twice daily. Results Efficacy evaluation was available for 80 patients (9 for PC, 28 for NSCLC, and 43 for CRC). Responses were 44.4% in arm 1, 61.5% in arm 2, and 77.8% in arm 3. There was a linear correlation between EGF concentrations and responses (p = .012). Quality of life (QoL) was assessed for 74 patients. Maximum changes in composite scores by Skindex‐16 after treatment were significantly different among arms (mean ± SD: −5.2 ± 8.6 for arm 1, −11.7 ± 14.2 for arm 2, and − 18.6 ± 17.7 for arm 3; p = .008). EGF arms showed significant improvement in emotions (p = .005) and functioning (p = .044) scores over the placebo arm. Conclusion EGF ointment is effective for managing ERSEs. It can also improve patients’ QoL compared with placebo. Clinical trial identification number. NCT02284139 Implications for Practice Patients with non‐small cell lung cancer, pancreatic cancer, or colorectal cancer who are treated with epidermal growth factor (EGF) receptor (EGFR) inhibitors may experience dermatologic reactions to their treatment. This study investigated the benefit of an EGF ointment in the treatment of these adverse events and observed the ointment to be effective in managing EGFR inhibitor‐related skin adverse events., Epidermal growth factor (EGFR) is an important target for antitumor therapy. This article evaluates the efficacy of EGF ointment for EGFR inhibitor‐related adverse events of the skin.

The purpose of this study was to use the same ice temperature and air temperature as the Pyeongchang Curling Stadium by using an Ice Chamber. Then, launch the stone at the same speed, and move according to the sweeping conditions (perpendicular to the axis of motion, along the axis of motion) of male and female elite curlers. The aim is to provide sports science information required for curling athletes by analyzing the distance of the stone, the change in the speed of a moved stone, the change in broom acceleration, and athletes&rsquo, muscle activity. The results of experiments conducted on four male and four elite female curlers are as follows. Under gender, the stone&rsquo, s movement distance was long after the sweeping of male athletes, and the speed of the stone was not different according to the conditions. The broom&rsquo, s acceleration did not show a difference in both the sweeping condition and the athlete&rsquo, s gender condition, and the muscle activity did not show a significant difference in both the sweeping condition and the gender condition. In summary, it is thought that male athletes moved the stone farther by raising the ice surface temperature by vertical load than female athletes. Also, there was no statistically significant difference in muscle activity results, but it was found that there was a specific pattern of muscle activity in the pushing and pulling motions during the sweeping of male and female athletes. It is expected to be used as primary data.

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 (pPAK4S474), 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 pPAK4S474. Expression of PAK4 and pPAK4S474 was compared with clinicopathological characteristics and survival after nephrectomy. Results PAK4 and pPAK4S474 were expressed predominantly in the nucleus. Overall, 57.3% (75/131) and 24.4% (29/119) of specimens exhibited high expression of pPAK4S474 and PAK4, respectively. High expression of pPAK4S474 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 pPAK4S474 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 pPAK4S474 expression was an independent predictor of recurrence in the subgroup with localized RCC. Conclusions pPAK4S474 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., Graphical Abstract

Purpose: We aimed to determine the influence of nutritional status on urinary metabolic abnormalities and stone recurrence in patients with urolithiasis. Materials and Methods: We analyzed data for 464 stone-formers and 464 propensity-score-matched control patients that had been collected between 2003 and 2015. Nutritional status was evaluated by use of the Controlling Nutritional Status (CONUT) score, and patients were placed into two CONUT score categories (0–1 and ≥2). Serum and 24-hour urinary metabolites were evaluated in 464 stone-formers. Kaplan–Meier and multivariate Cox regression analyses were performed to assess the influence of nutritional status on stone recurrence. Stone recurrence was defined as radiographic appearance of new stones during the follow-up period. Results: Stone-formers showed a higher prevalence of poor nutrition (CONUT score ≥2) than did the propensity-score-matched control patients (p

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., Graphical Abstract

Purpose We assessed the efficacy of adjuvant treatments in patients with peripelvic/periureteral fat-infiltrating (pT3b), nonmetastatic upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy. Methods and Materials The multicenter data of 222 patients with pT3bN0-x disease treated with radical nephroureterectomy were analyzed. The effects of adjuvant radiation therapy and chemotherapy on local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and cancer-specific survival (CSS) were evaluated. Results Adjuvant radiation therapy and chemotherapy were given to 39 (17.6%) and 74 patients (33.3%), respectively. Seventeen patients (7.7%) received concomitant adjuvant radiation therapy and chemotherapy. The median follow-up duration was 34.4 months. After adjusting for age, sex, tumor location, multifocality, tumor grade, presence of lymphovascular invasion, surgical margin, execution of node dissection, and other types of concomitant adjuvant treatment (radiation therapy or chemotherapy) through propensity-scored matching, adjuvant radiation therapy significantly reduced the local recurrence (5-year LRFS, 83.9 vs 54.2%; P = .001), distant metastasis (5-year DMFS, 72.1 vs 48.1%; P = .032), and cancer-specific death (5-year CSS, 76.4% vs 55.5%; P = .038) in pT3b UTUC. However, in the same condition, adjuvant chemotherapy did not reduce the local recurrence (5-year LRFS, 69.0% vs 66.2%; P = .786), distant metastasis (5-year DMFS, 65.3% vs 61.1%; P = .436), and cancer-specific death (5-year CSS, 67.9% vs. 67.9%; P = .458) in pT3b UTUC. Conclusions Our study suggests that adjuvant radiation therapy may be beneficial in patients with T3bN0-x UTUC; however, prospective clinical trials are needed to clarify this issue.

Preoperative chronic kidney disease (CKD) status may affect disease outcomes in patients with renal cell carcinoma (RCC). This study evaluated the influence of preoperative CKD status on clinicopathological features and prognosis in patients with RCC. Between 1999 and 2011, a total of 1855 patients underwent radical nephrectomy at various centers throughout Korea. Of these patients, 1655 had an estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2 (non-CKD group) and 200 patients had an eGFR ≥30 but

Pain is one of the most common and distressing symptoms in patients with cancer, with a high prevalence of 90%. Appropriate pain assessment is very important in managing cancer pain.The aims of this study were to (1) evaluate patient satisfaction with pain control therapy using a self-reporting pain assessment tool, (2) explore the usefulness of a self-reporting assessment tool for patients and physicians, and (3) evaluate patient perception of pain management and opioid analgesics.We enrolled a total of 587 South Korean adult cancer patients hospitalized for five days or more. Pain assessment using a self-reporting pain assessment tool was performed by patients themselves from Day 1 to Day 5. The average pain intensity on a numeric rating scale (NRS) and the frequency of breakthrough pain between Day 1 and Day 5 were recorded with a self-reporting pain assessment tool. We evaluated patient satisfaction with pain control and the usefulness of a self-reporting pain assessment tool for patients and physicians on Day 5.Among the 587 enrolled patients, 551, excluding 36 patients who violated inclusion criteria, were analyzed. The pain satisfaction rate was 79.5%, and only 6.2% of assessed patients had a negative pain management index (PMI). However, symmetry analysis for pain intensity between patient and physician showed low agreement (kappa=0.21). The patients with dissatisfaction for cancer pain control expressed negative attitudes toward using opioid analgesics and misconceptions regarding pain management. The satisfaction for using a self-reporting pain assessment tool was 79.2% in patients and 86.4% in physicians, respectively.The use of a self-reporting pain assessment tool as a communication instrument provides an effective foundation for evaluating pain intensity in cancer pain management. A more individualized approach to patient education about pain management may improve patient outcome.

Objective The main aim of this study was to evaluate the antitumor activity and safety of vinorelbine and gemcitabine combination chemotherapy in patients with primary refractory or recurrent platinum-resistant epithelial ovarian and primary peritoneal cancers. Methods Patients with platinum-resistant or primary refractory disease were eligible. Patients were allowed one prior chemotherapy for the treatment of platinum-resistant or refractory disease. Vinorelbine 25mg/m 2 , followed by gemcitabine 1000mg/m 2 , was administered intravenously on days 1 and 8 every 3weeks. Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 and cancer antigen 125 test (CA-125 criteria) were adopted to classify responses. Results 44 patients received the median of 4 (range, 1–24) treatments with fifteen (34.1%) receiving six or more cycles. The overall objective response rate was 22.7%. One patient (2.3%) had complete while 9 patients (20.4%) had partial responses with median duration of response of 5.9months. 17 patients (38.6%) had stable disease for a median of 3.3months. Median progression-free survival (PFS) was 3.4months and overall survival (OS) was 14.5months. Four (9.1%) patients were not assessable. Neutropenia was the most frequently encountered toxicity, with grade 3 or 4 observed in 22 patients (50.0%). Fifteen patients (34.1%) needed immediate dose reduction. No treatment related death was reported. Conclusions The combination chemotherapy with gemcitabine and vinorelbine achieved the primary end point of our clinical trial in management of platinum resistant recurrent ovarian cancer. However, further sophisticated dosing and scheduling of combination chemotherapy are needed because of a significant proportion of dose reduction.

There is growing interest in integrating electronic patient-reported outcome (PRO) measures into routine oncology practice for symptom monitoring. Here, we evaluated the feasibility and accessibility of electronic PRO measures using a smartphone (PRO-SMART) for cancer patients receiving routine chemotherapy. The proposed PRO-SMART application obtains daily personal health record (PHR) data from cancer patients via a smartphone. An analysis report of cumulative PHR data is provided to the clinician in a format suitable for upload to electronic medical records (EMRs). Cancer outpatients who had received at least two cycles of chemotherapy and who were scheduled for two more cycles were enrolled. Between February 2015 and December 2016, 111 patients were screened and 101 of these were included. One-hundred patients used PRO-SMART at least once and were included in the final analysis (90.1% overall accessibility among all screened patients). The number of symptomatic adverse events (AEs) related to chemotherapy recorded in EMRs (mean ± standard deviation [SD]) increased from 0.92 ± 0.80 to 2.26 ± 1.80 (P

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.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.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).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.

The purpose of this study was to evaluate the efficacy and safety of equine-derived bone matrix as a carrier for recombinant human platelet-derived growth factor BB (rhPDGF-BB) versus beta-tricalcium phosphate (β-TCP) for the treatment of intraosseous periodontal defects in adult patients. This study was performed on 32 adults with advanced periodontal disease. Eligible subjects were randomized in 1:1 ratio into a test (rhPDGF-BB-coated equine-derived bone matrix) or control group (rhPDGF-BB-coated β-TCP). Probing pocket depth (PD), clinical attachment level (CAL), gingival recession (GR), and defect depth on radiographs were measured at 2 weeks before surgery, on the day of surgery (DOS), and 6 months postsurgery (6MPS). The clinical and radiographic data were analyzed over the test period. Statistically significant PD reductions and CAL gain between baseline and 6MPS and between ODS and 6MPS were seen in both groups (P < .01). No statistically significant differences in PD reduction were found between groups. However, the test group showed significant CAL gain between DOS and 6MPS. The radiographic bone level change was statistically significant compared to baseline (P < .01) in both groups. The results suggested that equine-derived bone matrix is a viable, effective, and safe carrier scaffold for rhPDGF in periodontal defects.

Background Combination therapy with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) chemotherapy drastically improves survival of advanced pancreatic cancer patients. However, the efficacy of FOLFIRINOX as a second-line treatment after gemcitabine failure has not been tested prospectively. We investigated the feasibility and safety of attenuated FOLFIRINOX in patients with gemcitabine-refractory advanced pancreatic cancer. Methods A multicenter phase II prospective open-label, single-arm study was conducted at 14 hospitals. Patients with histologically proven invasive ductal pancreatic adenocarcinoma, a measurable or evaluable lesion, Eastern Cooperative Oncology Group performance status 0 or 1, adequate organ function, and aged 19 years or older were eligible. Attenuated FOLFIRINOX consisted of oxaliplatin 65 mg/m2, irinotecan 135 mg/m2, and leucovorin 400 mg/m2 injected intravenously on day 1 and 5-fluorouracil 2000 mg/m2 continuously infused intravenously over 46 h on days 1–2, repeated every 2 weeks. The primary endpoint was progression-free survival from the initiation of FOLFIRINOX. Secondary endpoints were the objective response rate, disease control rate, overall survival, safety, and tolerability. We estimated overall survival and progression-free survival using the Kaplan–Meier methods. Results We enrolled 39 patients from 14 institutions. The objective response rate was 10.3%, while the disease control rate was 64.1%. The 6-month and 1-year overall survival rates were 59.0% and 15.4%, respectively. Median progression-free survival and overall survival were 3.8 months (95% confidence interval [CI] 1.5–6.0 months) and 8.5 months (95% CI 5.6–11.4 months), respectively. Grade 3 or 4 adverse events were neutropenia (41.0%), nausea (10.3%), anorexia (10.3%), anemia (7.7%), mucositis (7.7%), pneumonia/pleural effusion (5.1%), and fatigue (5.1%). One treatment-related death attributable to septic shock occurred. Conclusion Attenuated FOLFIRINOX may be promising as a second-line therapy for gemcitabine-refractory pancreatic cancer.

The aim of this study was to assess the metabolic characteristics and risks of stone recurrence in young adult stone patients in Korea.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.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.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.

Purpose We aimed to the addition of synthetic 3-hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitor, simvastatin to capecitabine–cisplatin (XP) in patients with previously untreated advanced gastric cancer (AGC). Methods In this double-blind, placebo-controlled, phase III study, we enrolled patients aged 18 years or older with histological or cytological confirmed metastatic adenocarcinoma of the stomach or gastroesophageal junction (GEJ) at nine centres in Korea. Patients, stratified by disease measurability and participating site, were randomly assigned (1:1) to receive capecitabine 1000 mg/m2 twice daily for 14 days and cisplatin 80 mg/m2 on day 1 every 3 weeks plus either simvastatin 40 mg or placebo, once daily. Cisplatin was given for 8 cycles; capecitabine and simvastatin were administered until disease progression or unacceptable toxicities. This study is registered with ClinicalTrials.gov, number NCT01099085 . Results Between February 2009 and November 2012, 244 patients were enrolled and assigned to treatment groups (120 simvastatin, 124 placebo). Median progression free survival (PFS) for 120 patients allocated XP plus simvastatin was 5.2 months (95% confidence interval (CI) 4.3–6.1) compared with 4.63 months (95% CI 3.5–5.7) for 124 patients who were allocated to XP plus placebo (hazard ratio 0.930, 95% CI 0.684–1.264; p = 0.642). 63 (52.5%) of 120 patients in simvastatin group and 70 (56.4%) of 124 had grade 3 or higher adverse events. Conclusions Addition of 40 mg simvastatin to XP does not increase PFS in our trial, although it does not increase toxicity. Low dose of simvastatin (40 mg) to chemotherapy is not recommended in untargeted population with AGC.

Purpose: We assessed the impact of transobturator tape (TOT) treatment on overactive bladder (OAB) symptoms with a particular focus on nocturia in patients with mixed urinary incontinence (MUI). Materials and Methods: In this retrospective cohort study, the medical records of 237 women who underwent TOT surgery for the treatment of MUI were reviewed. Of these, 86 patients (36.4%) had preoperative nocturia. Patients with neurological diseases or sleep disorders that could affect the voiding pattern were excluded. Patients who were being treated with anticholinergics and antidiuretic hormones were also excluded, which left 70 subjects eligible for analysis. Pre- and postoperative evaluations consisted of a physical examination, 3-day frequency-volume chart, and health-related quality of life questionnaires (King’s health questionnaire, overactive bladder symptom score, and OAB-questionnaire). Results: TOT treatment resulted in an overall significant improvement in OAB symptoms including nocturia. Frequency-volume charts revealed that TOT treatment significantly decreased the actual number of nightly voids (ANV) and the nocturnal bladder capacity index (NBCi) in the entire cohort. However, in a subgroup of women with nocturnal polyuria, there was no significant change in ANV or NBCi after the sling operation. Correlation analysis of the whole cohort revealed that the postoperative changes in NBCi correlated positively with postoperative changes in ANV. The nocturia-persisting group was more likely to have nocturnal polyuria and lower preoperative functional bladder capacity compared with the nocturia-improved group (p=0.024 and p=0.023, respectively). Conclusions: Our results demonstrated that the TOT procedure resulted in an overall significant improvement in OAB symptoms including OAB-related nocturia in patients who presented with MUI.

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.

To assess the association between dyslipidemia and urolithiasis, a propensity score-matching study was performed.Fasting blood samples were taken, and serum lipid profiles were measured in 655 stone formers (SF) and 1965 propensity score-matched controls between 2005 and 2011. The controls, from a health-screening program, did not have a history of dyslipidemia or statin use and have any evidence of stone disease, as determined by abdominal radiography, ultrasonography examination. Propensity score-matching with respect to age, sex, and body mass index was used to minimize selection bias, and the logistic regression analysis was adjusted for other components of metabolic syndrome.Compared with controls, the SF group had significantly higher mean triglyceride and lower total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol levels (each P0.001). The SF group was also more likely to have hypertriglyceridemia and low HDL-cholesterolemia, and less likely to have hypercholesterolemia and high LDL cholesterolemia compared with controls (each P0.05). When adjusted for other components of metabolic syndrome including obesity, presence of diabetes mellitus or hypertension, the odds ratio (OR) for urinary stones appeared with hypercholesterolemia (OR=0.747, P=0.003), hypertriglyceridemia (OR=1.901, P0.001), low HDL cholesterolemia (OR=1.886, P0.001) and high LDL cholesterolemia (OR=0.610, P0.001).Our study implies that dyslipidemia may play a crucial part in urinary stone risk.

Introduction We evaluated the predictive value of glutathione S transferase mu ( GSTM1 ) and theta ( GSTT1 ) polymorphisms in early response to bacillus Calmette-Guerin (BCG) induction therapy in patients with primary non–muscle invasive bladder cancer. Methods G STM1 and GSTT1 polymorphisms were analyzed by multiplex polymerase chain reaction using blood genomic DNA from 135 patients with primary non–muscle invasive bladder cancer who were being treated with a single induction course of BCG. BCG nonresponsiveness (early BCG failure) was defined as a tumor recurrence or progression within 12 months after BCG induction therapy. The predictive value of GST polymorphisms was evaluated by Kaplan-Meier analysis and multivariate logistic regression models. Results Patients carrying a GSTT1 -positive genotype demonstrated a higher likelihood of early BCG failure regardless of cigarette smoking. After stratification based on the tumor stage and grade, the high-risk group (T1G3) with a GSTT1 -positive genotype showed a 14-fold higher risk of early BCG failure compared with those with a GSTT1 -null genotype. In a combined analysis of 2 genes, the GSTT1 -positive/ GSTM1 -null genotype had a higher risk of BCG nonresponsiveness compared with the GSTT1 -null/ GSTM1 -null genotype (odds ratio = 4.17, 95% CI: 1.54–11.26). By multivariate logistic regression analysis, the GSTT1- positive genotype was an independent predictor of early BCG failure (odds ratio = 3.67, 95% CI: 1.61–8.38). Kaplan-Meier estimates revealed a significant difference in disease-free survival depending on the GSTT1 genotype (log rank test, P = 0.038). Conclusions The results of this study suggest that the GSTT1 -positive genotype is an independent predictor of early BCG failure. These results can help determine whether patients would benefit from adjuvant BCG treatment or may require more aggressive alternative therapies.

Background We investigated whether genetic polymorphisms in the glutathione S transferase mu (GSTM1) and theta (GSTT1) genes modulated risk, disease progression and survival in primary muscle invasive bladder cancer (MIBC). Methods GSTM1 and GSTT1 polymorphisms were analysed by multiplex polymerase chain reaction (PCR) using blood genomic DNA in 110 MIBC patients and 220 gender- and age-matched healthy controls. The influence of the genetic polymorphisms on patient survival was evaluated by Kaplan–Meier survival curves and Cox Proportional Hazard models. We also evaluated whether cigarette smoking and treatment modality modified the association between genotype and prognosis. Results GSTM1-null individuals exhibited increased risk for MIBC and an association with cigarette smoking. GSTT1-null subjects showed significant disease progression and cancer-specific death. In the combined analysis, GSTT1-null genotype was an independent risk factor for disease progression and cancer specific death regardless of GSTM1 genotype. Significant differences in progression-free survival (PFS) and cancer-specific survival (CSS) were seen based on GSTT1 genotype. The survival impact of the GSTT1 genotype was only valid for smokers. The GSTT1-null genotype was an independent prognostic factor for shorter PFS in patients who received chemotherapy and those who did not undergo radical cystectomy. By multivariate Cox regression analysis, GSTT1-null genotype was a predictive factor for disease progression and cancer specific survival regardless of treatment modality. Conclusions The GSTM1-null genotype plays an important role in genetic susceptibility to MIBC and the GSTT1-null genotype is associated with disease progression and shorter survival in MIBC.

The appropriate management for asymptomatic renal stones remains unclear. We assessed the natural history and progression rate of such stones and identified clinical factors associated with an increased risk of stone related events.We retrospectively reviewed the medical records of 201 male and 146 female patients with asymptomatic renal stones. It was recommended that patients be followed every 6 months. Mean followup was 31 months (range 6 to 180). Patients were divided into 2 groups by stone related events, including spontaneous stone passage, flank pain, stone growth or the need for intervention during followup.Spontaneous passage occurred in 101 patients (29.1%). Of the patients 186 (53.6%) and 161 (46.4%) did and did not have stone related events, respectively. Of the whole cohort 85 patients (24.5%) required intervention but only 4.6% needed surgery. At 19 months after diagnosis 50% of the patients had a symptom. Those with stone related events were more likely to be younger (mean ± SD age 46.6 ± 12.7 vs 49.3 ± 12.6 years) and male, and have a stone history (p = 0.047, 0.017 and 0.014, respectively). Male gender significantly decreased the probability of freedom from stone related events (log rank test p = 0.0135) and it was an independent predictor of stone related events (HR 1.521, p = 0.009). Younger patients, and those with smaller stones and no stone growth were more likely to experience spontaneous passage and less likely to undergo intervention (each p0.05).Asymptomatic renal stones can be followed safely but long-term followup is necessary. Periodic followup and early intervention should be recommended in patients with risk factors.

The study evaluated the significance of 18F fluorodeoxyglucose (Ninety-five patients with histopathologically proven lymphoma, 7 Hodgkin's lymphoma and 88 non-Hodgkin's lymphoma, who underwentOf the 95 patients, 35 (36.8%) were histopathologically or clinically diagnosed with BM involvement of lymphoma. There were significant differences of BLR among lymphoma patients with/without BM involvement and normal subjects (P0.05). For all patients, high risk indicated by International Prognostic Index (IPI) score and Lmax were significantly associated with PFS on multivariate analysis (P0.05). For 60 patients without BM involvement, BM SUV and BLR were independent prognostic factors for PFS along with performance status and Lmax (p0.05). Among patients without BM involvement, highIn lymphoma patients without BM involvement

Purpose A fixed-dose combination of a stain and an antihypertensive drug may be useful for the treatment of patients with hypertension and hyperlipidemia. It may also improve patient drug compliance to help control risk factors of cardiovascular disease. This study was designed to evaluate the blood pressure–lowering and cholesterol-lowering effect of a fixed-dose combination of irbesartan-atorvastatin compared with monotherapy by either agent over an 8-week treatment period. Methods Patients with comorbid hypertension and hypercholesterolemia were screened for this randomized, double-blind, Phase III study. Eligible study patients were randomly assigned to test groups receiving a combination of irbesartan 300 mg and atorvastatin 40 mg or 80 mg (IRB300 + ATO40 and IRB300 + ATO80). Comparator groups comprised monotherapy groups with irbesartan 300 mg (IRB300) or atorvastatin 40 mg (ATO40) or atorvastatin 80 mg (ATO80), or placebo. Patients who were eligible at screening were subjected to a 4- to 6-week washout period before commencing 8 weeks of therapy per their assigned group. The primary efficacy end points were percent change in LDL-C and sitting diastolic blood pressure (DBP) levels from baseline to end of therapy. Tolerability profiles of combination therapy were compared with other groups. Findings A total of 733 patients with comorbid hypertension and hypercholesterolemia were screened for this study; 230 eligible patients were randomized to treatment. The mean age of patients was 58.9 (8.5) years, and their mean body mass index was 25.8 (3.2) kg/m2. More than two thirds (70.9%) of the study patients were male. Mean LDL-C and sitting DBP levels at baseline were 149.54 (29.19) mg/dL and 92.32 (6.03) mm Hg, respectively. Percent reductions in LDL-C after 8 weeks were 46.74% (2.06%) in the IRB300 + ATO40 group and 48.98% (2.12%) in the IRB300 + ATO80 group; these values were 47.13% (3.21%) and 48.30% (2.98%) in the ATO40 and ATO80 comparator groups. Similarly, a reduction in sitting DBP after 8 weeks was –8.50 (1.06) mm Hg in the IRB300 + ATO40 group and 10.66 (1.08) mm Hg in the IRB300 + ATO80 group compared with 8.40 (1.65) mm Hg in the IRB300 group. The incidence rate for treatment-emergent adverse events was 22.27% and was similar between the monotherapy and combination groups. Implications A once-daily combination product of irbesartan and atorvastatin provided an effective, safe, and more compliable treatment for patients with coexisting hypertension and hyperlipidemia. ClinicalTrials.gov identifier: NCT01442987.

This study sought to determine if runt-related transcription factor 3 (RUNX3) methylation could accurately predict the overall survival in patients with muscle invasive bladder cancer (MIBC). Forty-seven patients with a longer followup period (cohort 1; reported previously) were analyzed. Tumor samples (cohort 2; newly collected) were obtained from 139 MIBC patients. The prognostic significance of RUNX3 methylation was evaluated by Kaplan-Meier analysis and a multivariate Cox regression model. RUNX3 methylation affected the overall survival in cohort 1 (log-rank test; P = 0.030). Among the patients in cohort 2, RUNX3 promoter methylation was observed in 93 of the 139 tumor samples (66.9%). Kaplan-Meier estimates showed a significant difference in overall survival according to RUNX3 methylation (P = 0.020). By multivariate Cox regression analysis, positive RUNX3 methylation was an independent predictor of overall survival. These results suggest that RUNX3 promoter methylation is a significant prognostic factor for overall survival in MIBC patients.

Background: The phenotypic and genetic relationships between carotid intima-media thickness (CIMT) and estimated glomerular filtration rate (eGFR) or urinary albumin-creatinine ratio (ACR) were evaluated in Korean twins and families. Methods: We recruited 688 participants (296 individual twins and 392 singletons, age 30–74 years) who were without myocardial infarction and stroke among participants in the Healthy Twin Study. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. CIMT was measured using B-mode carotid ultrasound. Covariates were sex, Framingham risk scores, alcohol use, exercise, BMI, high-sensitivity C-reactive protein and triglycerides. Quantitative genetic and linear mixed analyses were performed. Results: In adjusted models there were associations between kidney function and CIMT with [beta] estimates ranging from –0.022 to –0.032 between eGFR and CIMT, and from 0.042–0.060 between ACR and CIMT. The covariate-adjusted heritabilities for eGFR, ACR and composite CIMT were 0.75, 0.32 and 0.45, respectively (p < 0.001). The adjusted genetic correlation between eGFR and CIMT was from –0.20 to –0.28 (p < 0.05), whereas there was no genetic correlation between ACR and CIMT. Conclusion: Kidney function is a surrogate marker of carotid atherosclerosis and further studies of the pleiotropic relationships between CIMT and eGFR are warranted.

To identify prognostic markers in nonmuscle invasive bladder cancer (NMIBC), the combined effect of RUNX3 and MGC17624 for predicting NMIBC progression was assessed. RUNX3 promoter methylation was examined using methylation specific-polymerase chain reaction (MS-PCR). MGC17624 mRNA expression was evaluated by real-time PCR. Patients were divided into three groups according to the status of the two genes and the prognostic effects of these markers were evaluated. The median follow-up period was 57.8 months (range, 9.1–189.7). The mRNA expression level of MGC17624 was significantly lower in patients with positive RUNX3 methylation than in those with negative methylation (p = 0.047). Kaplan–Meier estimates showed significant differences in time-to-progression between the genetic combination predictors (log-rank test; p < 0.001). Patients with a poor predictive combination were at a significantly higher risk for progression [Hazard ratio (HR), 22.579] than patients with a good predictive combination in multivariate Cox regression analysis. In the subgroup analysis, a poor predictive combination accurately estimated progression in patients with intravesical therapy (HR, 20.081) and in those who experienced recurrence (HR, 54.233). Assessment of the status of RUNX3 and MGC17624 in combination was identified as a reliable method for predicting NMIBC progression.

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.

This study investigated the safety and effectiveness of each type of central venous catheters (CVC) in patients with cancer. We prospectively enrolled patients with cancer who underwent catheterization involving a subclavian venous catheter (SVC), peripherally inserted central venous catheter (PICC), or chemo-port (CP) in our department. From March 2007 to March 2009, 116 patients underwent 179 episodes of catheterization. A SVC was inserted most frequently (46.4%). Fifty-four complications occurred (30.1%): infection in 23 cases, malpositioning or migration of the tip in 18 cases, thrombosis in eight cases, and bleeding in five cases. Malpositioning or migration of the tip occurred more frequently with a PICC (P0.001); infection occurred more often with a tunneled catheter (P=0.028) and was observed more often in young patients (P=0.023). The catheter life span was longer for patients with solid cancer (P=0.002) than for those with hematologic cancer, with a CP (P0.001) than a PICC or SVC, and for an indwelling catheter with image guidance (P=0.014) than a blind procedure. In conclusion, CP is an effective tool for long term use and the fixation of tip is important for the management of PICC.

Involvement of the central nervous system is very uncommon in multiple myeloma, observed in approximately 1% of the multiple myeloma patients. We report a case of central nervous system myelomatosis with complex chromosome aberrations in a 62-yr-old female patient, who had previously been diagnosed as multiple myeloma. Fluorescent in situ hybridization revealed 13q deletion, p53 gene deletion and IGH/FGFR3 rearrangement and chromosomal study showed complex chromosome aberrations. After four cycles of chemotherapy, the patient was admitted to the hematology department with severe headache. Plasma cells were found in the cerebrospinal fluid (CSF), and CSF immunoelectrophoresis revealed abnormal precipitin arcs against anti-IgG and anti-lambda antisera. She was given systemic chemotherapy and eight courses of intrathecal chemotherapy, which cleared plasma cells in the CSF. Two months later, she was given autologous stem cell transplantation. Three months after stem cell transplantation, central nervous system myelomatosis progressed to plasma cell leukemia and two months later,the patient expired. (Korean J Lab Med 2010;30:334-8)

OBJECTIVES To assess the changes and sex-specific differences in urinary metabolic risk factors with time. METHODS We performed a retrospective analysis of 619 patients with first-time calcium stone formation (SF) with complete metabolic assessments, who had been diagnosed and treated from 1994 to 2007 at our institution. Patients with SF were categorized into 2 groups according to the date of initial diagnosis: group 1 (1994-1999, n = 353 [57.0%]) and group 2 (2000-2007, n = 266 [43%]). RESULTS The incidence of obesity was greater in group 2 than in group 1, and this difference was statistically significant among male patients with SF. The urinary pH and total urine volume were lower and the excretion of uric acid was greater in group 2 than in group 1. The incidence of metabolic abnormalities such as low urine volume was more common in group 2 than in group 1. The incidence of hyperuricosuria was increased in male patients with SF in group 2 compared with that in the men in group 1. However, no significant differences were found in the incidence of hyperuricosuria in the female patients with SF between groups 1 and 2. CONCLUSIONS The pattern of urinary lithogenic factors in Korean patients with SF has changed with time. Hyperuricosuria has become more prevalent in recent years. We found a high prevalence of hyperuricosuria in men, which might have been due to the increased incidence of obesity in this subgroup.

The aim of this study is to investigate the efficacy and safety of gemcitabine and oxaliplatin combination chemotherapy as first-line therapy in patients with inoperable biliary tract cancer (BTC). The treatment of this non-randomized phase II study consisted of gemcitabine 1,000 mg/m2 intravenously (i.v.) on day 1 and oxaliplatin 85 mg/m2 i.v. on day 2 every 2 weeks until disease progression, unaccep toxicity or patients’ refusal. From Sept 2006 to Oct 2007, 40 patients were enrolled. In the ITT analysis, the objective response rate was 15.0% and the disease control rate was 52.5%. The median overall survival (95% CI) was 8.5 months (6.4–10.7) and the time to progression was 4.2 months (0.5–7.9). For the 305 cycles, observed grade 3/4 toxicity was uncommon. Gemcitabine and dose adjusted oxaliplatin combination chemotherapy had moderate anti-tumor activity and was well tolerated as a first-line treatment for patients with inoperable BTC.

To assess the risk factors of positive surgical margins (PSM) and the influence of margin status on recurrence in pT1 clear cell renal cell carcinoma (RCC) following partial nephrectomy (PN).Patients (1,831) with pathologically confirmed stage T1 clear cell RCC were retrospectively analyzed following PN at eight institutions in Korea between 1999 and 2011. Demographics, operative data, pathological margin status, and site of recurrence were analyzed.Resection margins were positive in 31 patients (1.7% of the cohort) on final pathology. None of the clinicopathological parameters were significantly related to the marginal status (all P 0.05). During a median follow-up of 32.5 months, local recurrences were observed in 0.4% of negative surgical margins. There was no local recurrence in any of the cases with PSM. Distant recurrences developed in 1.7% of negative surgical margins and 3.2% of PSM. There were no significant differences in recurrence-free survival by margin status (P = 0.566).Our multi-institutional data suggest that marginal status does not influence tumor recurrence risk in pT1 clear cell RCC after PN. Careful surveillance seems to be a sufficient strategy in this clinical scenario. J. Surg. Oncol. 2016;114:70-74. © 2016 Wiley Periodicals, Inc.