Publications by authors named "Cheol Kwak"

311 Publications

Ultrathin rGO-wrapped free-standing bimetallic CoNiS-carbon nanofibers: an efficient and robust bifunctional electrocatalyst for water splitting.

Nanotechnology 2020 Apr 17;31(27):275402. Epub 2020 Mar 17.

Department of Energy and Material Engineering, Dongguk University, Seoul 04620, Republic of Korea.

Electrochemical water splitting represents an ideal strategy for producing clean hydrogen as an energy carrier that serves as an alternative to fossil fuels. As an effective method for hydrogen production, an efficient inexpensive multifunctional electrocatalyst with high durability is designed. Herein, we describe the heterostructural design of a three-dimensional catalytic network with self-embedded CoNiS nanograins grown on electrospun carbon nanofibers (CoNiS-CNFs) with anchored thin-layer reduced graphene oxide. This is achieved via facile electrospinning followed by carbonization, low-temperature sulfidation, and surface functionalization. As a bifunctional catalyst, CoNiS-CNFs exhibited robust high activity toward the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in an alkaline medium. The anchored ultrathin graphene oxide layer promoted the stability and durability of the catalytic network with an efficient path for the transportation of electrons. The rGO-anchored CoNiS-CNFs yielded overpotential values of 228 mV and 205 mV for the HER and OER, respectively, that drives a current density of 20 mA cm in an alkaline medium. Notably, the excellent electrochemical properties are attributed to the functional effect of the CoNiS on the CNF network. The ultrathin feature of rGO improved the durability of the catalytic network. Moreover, using the rGO-anchored CoNiS-CNFs as a cathode and anode in a two-electrode water splitting system required a cell voltage of only 1.55 V to reach a current density of 10 mA cm. These CNFs exhibited outstanding durability for 48 h. The present work offers new insight for the design of a catalytic network with a non-noble metal catalyst that exhibits excellent electrocatalytic activity and durability on the metal sulfides in overall water splitting.
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http://dx.doi.org/10.1088/1361-6528/ab8086DOI Listing
April 2020

Impact of perioperative blood transfusion on oncologic outcomes in patients with nonmetastatic renal cell carcinoma treated with curative nephrectomy: A retrospective analysis of a large, single-institutional cohort.

Investig Clin Urol 2020 03 17;61(2):136-145. Epub 2020 Feb 17.

Department of Urology, Dongguk University Ilsan Medical Center, Goyang, Korea.

Purpose: To evaluate the impact of perioperative blood transfusion (PBT) on oncologic outcomes after surgery in patients with nonmetastatic renal cell carcinoma (RCC).

Materials And Methods: This retrospective review included 2,329 patients who underwent partial or radical nephrectomy for localized RCC in a single institution from 2000 to 2014. PBT was defined as transfusion of allogeneic packed red blood cells (pRBCs) during nephrectomy or within the preoperative or postoperative hospitalization period. Oncologic outcomes of interest were recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS).

Results: PBT was performed in 275 patients (11.8%). In the multivariable logistic regression analysis, symptomatic presentation, advanced age at surgery, higher preoperative serum creatinine, and lower preoperative hemoglobin were independent preoperative risk factors for PBT (all p<0.05). Kaplan-Meier plots revealed that transfused patients showed poorer 5-year RFS (65.1% vs. 91.2%, p<0.001), OS (71.4% vs. 92.8%, p<0.001), and CSS (74.0% vs. 95.5%, p<0.001) than nontransfused patients. However, in the multivariable Cox regression analyses, PBT was not significantly associated with RFS, OS, or CSS. In multivariable analyses involving transfused patients only (n=275), an higher number of pRBC units was an independent predictor of worse OS (hazard ratio [HR], 1.043; 95% confidence interval [CI], 1.008-1.078; p=0.016) and CSS (HR, 1.066; 95% CI, 1.033-1.100; p<0.001).

Conclusions: The results of this study are inconclusive in that the influence of PBT on survival outcomes could not be determined in the multivariate analysis. However, increasing pRBC units in transfused patients might be a concern in light of worse OS and CSS. Therefore, efforts to limit PBT overuse seem necessary to improve postoperative survival in patients with RCC.
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http://dx.doi.org/10.4111/icu.2020.61.2.136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052423PMC
March 2020

Targeted next-generation sequencing for locally advanced prostate cancer in the Korean population.

Investig Clin Urol 2020 03 10;61(2):127-135. Epub 2020 Feb 10.

Department of Urology, Seoul National University College of Medicine, Seoul, Korea.

Purpose: This study aimed to evaluate the feasibility of pan-cancer panel analysis for locally advanced prostate cancer in the Korean population.

Materials And Methods: We analyzed 20 patients with locally advanced prostate cancer who underwent radical prostatectomy. A pan-cancer panel (1.9 Mbp) developed by Seoul National University Hospital (SNUH), composed of 183 target genes, 23 fusion genes, and 45 drug target regions was used for this analysis. We compared the SNUH pan-cancer panel results with The Cancer Genome Atlas (TCGA) database to search for different mutations in the Korean population. Clinical data were analyzed with univariate and multivariate analysis, and p-values <0.05 were considered statistically significant. Kaplan-Meier curve and log-rank tests were performed to evaluate survival.

Results: The average age of the patients and initial prostate-specific antigen values were 69.3±7.8 years and 66.3±16.9 ng/dL, respectively. Average sequencing depth was 574.5±304.1×. Ninety-nine genetic mutations and 5 fusions were detected. (25%), (20%), and (15%) were frequently detected. fusions were recurrently detected in 20% of the patients, with and as novel fusion partners. mutation was frequently detected in this study, but not in the TCGA database. Multivariate analysis showed mutation as an independent prognostic factor for biochemical recurrence (hazard ratio, 9.84; p=0.03).

Conclusions: The pan-cancer panel comprising genes related to prostate cancer is a useful tool for evaluating genetic alterations in locally advanced prostate cancers. Our results suggest that the mutation is associated with biochemical recurrence in the Korean population.
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http://dx.doi.org/10.4111/icu.2020.61.2.127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052421PMC
March 2020

Kidney residency of VISTA-positive macrophages accelerates repair from ischemic injury.

Kidney Int 2020 05 17;97(5):980-994. Epub 2019 Dec 17.

Kidney Research Institute, Seoul National University, Seoul, Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. Electronic address:

Tissue-resident macrophages have unique tissue-specific functions in maintaining homeostasis and resolving inflammation. However, the repair role and relevant molecules of kidney-resident macrophages after ischemic injury remain unresolved. To this end, mice without kidney-resident R1 macrophages but containing infiltrating monocyte-derived R2 macrophages were generated using differential cellular kinetics following clodronate liposome treatment. When ischemia-reperfusion injury was induced in these mice, late phase repair was reduced. Transcriptomic and flow cytometric analyses identified that V-domain Ig suppressor of T cell activation (VISTA), an inhibitory immune checkpoint molecule, was constitutively expressed in kidney-resident R1 macrophages, but not in other tissue-resident macrophages. Here, VISTA functioned as a scavenger of apoptotic cells and served as a checkpoint to control kidney-infiltrating T cells upon T cell receptor-mediated stimulation. Together these functions improved the repair process after ischemia-reperfusion injury. CD14 CD33 mononuclear phagocytes of human kidney also expressed VISTA, which has similar functions to the mouse counterpart. Thus, VISTA is upregulated in kidney macrophages in a tissue-dependent manner and plays a repair role during ischemic injury.
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http://dx.doi.org/10.1016/j.kint.2019.11.025DOI Listing
May 2020

Robust Association between Acute Kidney Injury after Radical Nephrectomy and Long-term Renal Function.

J Clin Med 2020 Feb 25;9(3). Epub 2020 Feb 25.

Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea.

The association between acute kidney injury (AKI) and long-term renal function after radical nephrectomy has not been evaluated fully. We reviewed 558 cases of radical nephrectomy. Postoperative AKI was defined by the Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria. Values of estimated glomerular filtration rate (eGFR) were collected up to 36 months (median 35 months) after surgery. The primary outcome was new-onset chronic kidney disease (CKD) stage 3a or higher or all-cause mortality within three years after nephrectomy. The functional change ratio (FCR) of eGFR was defined as the ratio of the most recent GFR (24-36 months after surgery) to the new baseline during 3-12 months. A multivariable Cox proportional hazard regression analysis for new-onset CKD and a multivariable linear regression analysis for FCR were performed to evaluate the association between AKI and long-term renal outcomes. A correlation analysis was performed with the serum creatinine ratio and used to determine AKI and FCR. AKI occurred in 43.2% ( = 241/558) and our primary outcome developed in 40.5% ( = 226/558) of patients. The incidence of new-onset CKD was significantly higher in patients with AKI than those without at all follow-up time points after surgery. The Cox regression analysis showed a graded association between AKI and our primary outcome (AKI stage 1: Hazard ratio 1.71, 95% confidence interval 1.25-2.32; AKI stage 2 or 3: Hazard ratio 2.72, 95% confidence interval 1.78-4.10). The linear regression analysis for FCR showed that AKI was significantly associated with FCR (β = -0.168 ± 0.322, = 0.011). There was a significant negative correlation between the serum creatinine ratio and FCR. In conclusion, our analysis demonstrated a robust and graded association between AKI after radical nephrectomy and long-term renal functional deterioration.
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http://dx.doi.org/10.3390/jcm9030619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141119PMC
February 2020

Electroactive Ultra-Thin rGO-Enriched FeMoO Nanotubes and MnO Nanorods as Electrodes for High-Performance All-Solid-State Asymmetric Supercapacitors.

Nanomaterials (Basel) 2020 Feb 9;10(2). Epub 2020 Feb 9.

Department of Energy and Material Engineering, Dongguk University-Seoul, Seoul 04620, Korea.

A flexible asymmetric supercapacitor (ASC) with high electrochemical performance was constructed using reduced graphene oxide (rGO)-wrapped redox-active metal oxide-based negative and positive electrodes. Thin layered rGO functionality on the positive and the negative electrode surfaces has promoted the feasible surface-active sites and enhances the electrochemical response with a wide operating voltage window. Herein we report the controlled growth of rGO-wrapped tubular FeMoO nanofibers (NFs) via electrospinning followed by surface functionalization as a negative electrode. The tubular structure offers the ultrathin-layer decoration of rGO inside and outside of the tubular walls with uniform wrapping. The rGO-wrapped tubular FeMoO NF electrode exhibited a high specific capacitance of 135.2 F g in NaSO neutral electrolyte with an excellent rate capability and cycling stability (96.45% in 5000 cycles) at high current density. Meanwhile, the hydrothermally synthesized binder-free rGO/MnO nanorods on carbon cloth (rGO-MnO@CC) were selected as cathode materials due to their high capacitance and high conductivity. Moreover, the ASC device was fabricated using rGO-wrapped FeMoO on carbon cloth (rGO-FeMoO@CC) as the negative electrode and rGO-MnO@CC as the positive electrode (rGO-FeMoO@CC/rGO-MnO@CC). The rationally designed ASC device delivered an excellent energy density of 38.8 W h kg with a wide operating voltage window of 0.0-1.8 V. The hybrid ASC showed excellent cycling stability of 93.37% capacitance retention for 5000 cycles. Thus, the developed rGO-wrapped FeMoO nanotubes and MnO nanorods are promising hybrid electrode materials for the development of wide-potential ASCs with high energy and power density.
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http://dx.doi.org/10.3390/nano10020289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075176PMC
February 2020

Enzalutamide in chemotherapy-naive patients with metastatic castration-resistant prostate cancer: A retrospective Korean multicenter study in a real-world setting.

Investig Clin Urol 2020 01 10;61(1):19-27. Epub 2019 Dec 10.

Department of Urology, Chonnam National University Medical School, Gwangju, Korea.

Purpose: This study aimed to evaluate the clinical efficacy of enzalutamide in chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) patients using real-world data from Korean patients.

Materials And Methods: We retrospectively reviewed the medical records of 199 chemotherapy-naïve patients with mCRPC at 13 tertiary centers in Korea between 2014 and 2017. All patients received enzalutamide daily and 89 patients received concurrent androgen deprivation therapy (ADT).

Results: The median age of the patients was 74 years. Initial results showed that 81.5% of the patients had Gleason score ≥8 and 33.3% of the patients had European Cooperative Oncology Group Performance Status 0. The overall mortality rate was 12%. The median OS was not archieved and 76.7% of patients were alive at 30 months. Median time until PSA progression was 6 months. The overall survival rate at 2 years was significantly higher (84.6% vs. 71.7%, p=0.015) and the duration of PSA progression-free survival was significantly longer (8.0 vs. 4.6 months, p=0.008) in patients receiving concurrent ADT than in those receiving enzalutamide alone. The incidence of adverse events of grade 3 or higher was 1.7%. Multivariate Cox proportional hazard analysis indicated that ADT administered concurrently with enzalutamide significantly improved the overall survival (hazard ratio, 0.346; 95% confidence interval, 0.125-0.958).

Conclusions: Enzalutamide is effective and safe for chemotherapy-naïve patients with mCRPC. Furthermore, the overall survival was significantly higher in patients receiving enzalutamide and concurrent ADT than in patients receiving enzalutamide alone.
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http://dx.doi.org/10.4111/icu.2020.61.1.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946821PMC
January 2020

Clinical Significance of Pre-treated Neutrophil-Lymphocyte Ratio in the Management of Urothelial Carcinoma: A Systemic Review and Meta-Analysis.

Front Oncol 2019 16;9:1365. Epub 2019 Dec 16.

Department of Urology, Seoul National University College of Medicine, Seoul, South Korea.

We performed a study-level meta-analysis to summarize the current evidence on the correlation between pretreatment neutrophil-to-lymphocyte ratios (NLR) and oncological outcomes in each type of management for urothelial carcinoma. All articles published until February 2017 in PubMed, Scopus, and EMBASE database were collected and reviewed. The current evidence on correlations between pretreatment NLR and oncological outcomes in each type of management for urothelial carcinoma, including transurethral resection of bladder tumor (TURBT), radical cystectomy (RCx), chemotherapy (CTx), and nephroureterectomy (NUx), were summarized. Thirty-eight studies containing clinical information on 16,379 patients were analyzed in this study. Pooled hazard ratios (HR) and odds ratios (OR) with 95% confidence intervals were calculated after weighing each study. Heterogeneity among the studies and publication bias were assessed. Pretreatment NLR was significantly associated with muscle invasiveness (OR: 4.27), recurrence free survival (RFS, HR: 2.32), and progression-free survival (PFS, HR: 2.45) in TURBT patients. In the RCx patients, high NLR was negatively associated with both disease status (extravesical extension and lymph-node positivity, OR: 1.14 and 1.43, respectively) and oncological outcomes [overall survival (OS), PFS], and cancer specific survival (CSS, HR: 1.18, 1.12, and 1.35, respectively). Pretreatment NLR was negatively correlated with pathologic downstaging (OR: 0.79) and positively correlated with PFS (HR: 1.30) and OS (HR: 1.44) in CTx patients. For patients who underwent NUx, pretreatment NLR was significantly associated with OS (HR: 1.72), PFS (HR: 1.63), and CSS (HR: 1.68). Pretreatment NLR is a useful biomarker for disease aggressiveness, oncological outcome, and treatment response in the management of patients with urothelial carcinoma. More evidence is needed to clarify these results.
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http://dx.doi.org/10.3389/fonc.2019.01365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927426PMC
December 2019

Differential Expression of Glucose Transporters and Hexokinases in Prostate Cancer with a Neuroendocrine Gene Signature: A Mechanistic Perspective for F-FDG Imaging of PSMA-Suppressed Tumors.

J Nucl Med 2020 06 5;61(6):904-910. Epub 2019 Dec 5.

Department of Biomedical Sciences, University of Windsor, Windsor, Ontario, Canada

Although the incidence of de novo neuroendocrine prostate cancer (PC) is rare, recent data suggest that low expression of prostate-specific membrane antigen (PSMA) is associated with a spectrum of neuroendocrine hallmarks and androgen receptor (AR) suppression in PC. Previous clinical reports indicate that PCs with a phenotype similar to neuroendocrine tumors can be more amenable to imaging by F-FDG than by PSMA-targeting radioligands. In this study, we evaluated the association between neuroendocrine gene signature and F-FDG uptake-associated genes including glucose transporters (GLUTs) and hexokinases, with the goal of providing a genomic signature to explain the reported F-FDG avidity of PSMA-suppressed tumors. Data-mining approaches, cell lines, and patient-derived xenograft models were used to study the levels of 14 members of the family (encoding GLUT proteins), 4 members of the hexokinase family (genes - and ), and PSMA ( gene) after AR inhibition and in correlation with neuroendocrine hallmarks. Also, we characterize a neuroendocrine-like PC (NELPC) subset among a cohort of primary and metastatic PC samples with no neuroendocrine histopathology. We measured glucose uptake in a neuroendocrine-induced in vitro model and a zebrafish model by nonradioactive imaging of glucose uptake using a fluorescent glucose bioprobe, GB2-Cy3. This work demonstrated that a neuroendocrine gene signature associates with differential expression of genes encoding GLUT and hexokinase proteins. In NELPC, elevated expression of (encoding glucokinase protein) and decreased expression of correlated with earlier biochemical recurrence. In tumors treated with AR inhibitors, high expression of and low expression of correlated with neuroendocrine histopathology and PSMA gene suppression. GLUT12 suppression and upregulation of glucokinase were observed in neuroendocrine-induced PC cell lines and patient-derived xenograft models. A higher glucose uptake was confirmed in low-PSMA tumors using a GB2-Cy3 probe in a zebrafish model. A neuroendocrine gene signature in neuroendocrine PC and NELPC associates with a distinct transcriptional profile of GLUTs and hexokinases. PSMA suppression correlates with GLUT12 suppression and glucokinase upregulation. Alteration of F-FDG uptake-associated genes correlated positively with higher glucose uptake in AR- and PSMA-suppressed tumors. Zebrafish xenograft tumor models are an accurate and efficient preclinical method for monitoring nonradioactive glucose uptake.
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http://dx.doi.org/10.2967/jnumed.119.231068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262227PMC
June 2020

Patients with Biopsy Gleason Score 3 + 4 Are Not Appropriate Candidates for Active Surveillance.

Urol Int 2020 6;104(3-4):199-204. Epub 2019 Nov 6.

Department of Urology, SMG-SNU Boramae Medical Center, College of Medicine, Seoul National University, Seoul, Republic of Korea,

Objective: The aim of this study was to evaluate the feasibility of including patients with biopsy Gleason score (bGS) 3 + 4 prostate cancer in an active surveillance (AS) protocol.

Methods: A total of 615 patients underwent a radical prostatectomy and satisfied the following requirements: prostate-specific antigen ≤10 ng/dL, clinical stage T1c or T2a, 2 or fewer positive biopsy cores, and bGS 6 or 3 + 4 prostate cancer. The patients were divided into two groups according to their bGS (bGS 6 group, n =534; bGS 3 + 4 group, n = 81).

Results: The adverse pathological features were significantly higher in the bGS 3 + 4 group (16.7 vs. 49.4%, p< 0.001). Biochemical recurrence (BCR)-free survival was also significantly lower in this group (p < 0.001). In a multivariate analysis, clinical stage (odds ratio [OR] 2.026, p =0.007), maximum percentage of biopsy core involvement (OR 1.015, p = 0.014), and bGS (OR 1.913, p = 0.030) were independent risk factors for adverse pathological features. However, the bGS was the only variable to forecast BCR (hazard ratio 3.567, p < 0.001).

Conclusions: A bGS 3 + 4 was the leading risk factor for a worse postoperative prognosis. Therefore, patients with a bGS 3 + 4 are not appropriate candidates for AS.
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http://dx.doi.org/10.1159/000503888DOI Listing
January 2021

BCG instillation versus radical cystectomy for high-risk NMIBC with squamous/glandular histologic variants.

Sci Rep 2019 10 24;9(1):15268. Epub 2019 Oct 24.

Department of Urology Seoul National University College of Medicine, Seoul, South Korea.

This study aims to evaluate the effect of Bacillus Calmette-Guérin (BCG) instillation and radical cystectomy on high-risk NMIBC with squamous or glandular variants. We retrospectively reviewed the data of high-risk (T1 or CIS or HG or TaG1/G2 with multiple, recurrent, large tumor) NMIBC patients from January 2000 to December 2017. Comparative analysis of radical cystectomy, intravesical BCG, and observation groups was conducted in high-risk NMIBC with squamous or glandular histologic variants. Among the 1263 high-risk NMIBC patient, 62 (4.9%) were reported squamous or glandular histologic variants. Thirty patients underwent BCG instillation and 15 patients were subjected to radical cystectomy. Statistically significant differences were found between the three treatment groups in terms of underlying hypertension (p = 0.031), T stage (p = 0.022) and tumor multiplicity (p = 0.019). Similar 5-year OS (p = 0.893) and CSS (p = 0.811) were observed in each of BCG instillation and radical cystectomy group. BCG instillation showed survival benefit in both OS (p = 0.019) and CSS (p = 0.038) than in the observation group. In high-risk patients diagnosed with NMIBC bladder cancer with squamous or glandular histologic variants, both intravesical BCG and radical cystectomy showed survival gain. In conclusion, BCG instillation represents an appropriate treatment option in high-risk NMIBC with squamous or glandular histologic variant.
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http://dx.doi.org/10.1038/s41598-019-51889-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813340PMC
October 2019

The age-adjusted Charlson comorbidity index as a predictor of overall survival of surgically treated non-metastatic clear cell renal cell carcinoma.

J Cancer Res Clin Oncol 2020 Jan 12;146(1):187-196. Epub 2019 Oct 12.

Department of Urology, Chungbuk National University College of Medicine, 1st Chungdae-ro, Seowon-gu, Cheongju, Chungbuk, 28644, South Korea.

Purpose: 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).

Methods: 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.

Results: 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 < 0.001) and overall survival (log-rank test, P < 0.001), but not with recurrence-free survival (log-rank test, P = 0.134). Multivariate Cox regression analyses identified an AACI score as an independent predictor of overall survival (hazard ratio, 6.870; 95% confidence interval, 2.049-23.031; P = 0.002). The AACI score was a better discriminator of overall survival than the Charlson comorbidity index score.

Conclusions: AACI scores may enable more tailored, individualized management strategies for patients with surgically treated non-metastatic ccRCC.
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http://dx.doi.org/10.1007/s00432-019-03042-7DOI Listing
January 2020

Does reduced E-cadherin expression correlate with poor prognosis in patients with upper tract urothelial cell carcinoma?: A systematic review and meta-analysis.

Medicine (Baltimore) 2019 Oct;98(40):e17377

Department of Urology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea.

Background: E-cadherin has emerged as a prognostic factor of urothelial cell carcinoma. In the present work we investigate the relationship between expression of E-cadherin and clinical outcomes, following radical nephroureterectomy for upper tract urothelial cell carcinoma.

Methods: We systematically searched PubMed, Embase, Cochrane Library, and Web of Science databases to identify eligible studies published until July 2017.

Result: Six studies were included in the meta-analysis, with a total of 1014 patients. The pooled hazard ratio (HR) for recurrence-free survivor was 0.69 (95% confidence interval [CI], 0.44-1.09, I = 63%, P = .04). Also, reduced E-cadherin was not significantly associated with poor cancer-specific survivor (pooled HR, 1.40; 95% CI, 0.66-1.43, I = 54%, P = .11). The pooled HR for overall survivor was not statistically significant (pooled HR, 0.68; 95% CI, 0.32-1.46, I = 80%, P = .007). The results of the Begg and Egger tests suggested that publication bias was not evident in this meta-analysis.

Conclusions: Reduced E-cadherin expression did not appear to be significantly associated with disease prognosis after nephroureterectomy in the meta-analysis. However, further high quality, prospective studies are warranted to better address this issue.
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http://dx.doi.org/10.1097/MD.0000000000017377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783224PMC
October 2019

Retrospective Multicenter Long-Term Follow-up Analysis of Prognostic Risk Factors for Recurrence-Free, Metastasis-Free, Cancer-Specific, and Overall Survival After Curative Nephrectomy in Non-metastatic Renal Cell Carcinoma.

Front Oncol 2019 4;9:859. Epub 2019 Sep 4.

Department of Urology, Urologic Cancer Center, Research Institute and Hospital of National Cancer Center, Goyang-si, South Korea.

We evaluated prognostic risk factors of recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) outcomes in patients with non-metastatic renal cell carcinoma (nmRCC) after curative nephrectomy during long-term follow-up. The medical records of 4,260 patients with nmRCC who underwent curative nephrectomy between 2000 and 2012 from five Korean institutions and follow-up after postoperative 1 month until December 2017 were retrospectively analyzed for RFS, MFS, OS, and CSS. During the median 43.86 months of follow-up, 342 recurrences, 127 metastases, and 361 deaths, including 222 cancer-specific deaths, were reported. In addition to the unreached median survival of RFS and MFS, the median OS and CSS times were 176.75 and 227.47 months, respectively. Multivariable analyses showed that nephrectomy type (laparoscopy vs. open), pathological T stages, and nuclear grade were common significant risk factors for survival, and the baseline ASA, hemoglobin, and pathological N stage were common factors only for RFS, OS, and CSS ( < 0.05). Further, tumor necrosis for MFS; platelet count, extent (partial vs. radical) of surgery, and lymphovascular invasion for RFS; baseline diabetes, hypertension, age, body mass index, extent of surgery, and pathological sarcomatoid differentiation for OS; and baseline diabetes, hypertension, body mass index, and pathological sarcomatoid differentiation for CSS were additionally significant risk factors ( < 0.05). RFS, MFS, OS, and CSS were significantly different depending on the pathological T stages ( < 0.05). In conclusion, this large-numbered, long-term follow-up study revealed significant factors affecting the survival of patients with nephrectomized nmRCC.
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http://dx.doi.org/10.3389/fonc.2019.00859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738012PMC
September 2019

De Ritis Ratio (Aspartate Transaminase/Alanine Transaminase) as a Significant Prognostic Factor in Patients Undergoing Radical Cystectomy with Bladder Urothelial Carcinoma: A Propensity Score-Matched Study.

Dis Markers 2019 27;2019:6702964. Epub 2019 Aug 27.

Department of Urology, Seoul National University Hospital, Seoul, Republic of Korea.

Introduction: To investigate the correlation between preoperative De Ritis ratio (aspartate transaminase (AST)/alanine transaminase (ALT)) and postoperative outcome in patients with urothelial cell carcinoma (UC) treated with radical cystectomy.

Materials And Methods: We analyzed the clinical and pathological data of 771 patients who underwent radical cystectomy for bladder UC. Patients were divided into two groups according to the optimal value of AST/ALT ratio. The effect of the AST/ALT ratio was analyzed using the Kaplan-Meier method and Cox regression hazard models for patients' cancer-specific survival (CSS), overall survival (OS), and recurrence-free survival (RFS). In addition, propensity score matching of 1 : 1 was performed between the two groups.

Results: Median follow-up was 84.0 (36-275) months. Mean age was 64.8 ± 10.0 years. According to the receiver operating characteristic (ROC) analysis, the optimal threshold of the AST/ALT ratio was 1.1. In Kaplan-Meier analyses, the high AST/ALT group showed worse outcomes in CSS and OS (all < 0.001). Also, RFS ( = 0.001) in the Cox regression models of clinical and pathological parameters was used to predict CSS, OS, and AST/ALT ratio (HR 2.15, 95% CI 1.23-3.73, = 0.007) and pathological T stage (HR 4.80, 95% CI 1.19-19.28, = 0.003). To predict OS and AST/ALT ratio (HR 2.05, 95% CI 1.65-2.56, < 0.001), pathological T stage (HR 2.96, 95% CI 0.57-17.09, = 0.037) and positive lymph node (HR 1.71, 95% CI 1.50-1.91, = 0.021) were determined as independent prognostic factors.

Conclusion: Preoperative AST/ALT ratio could be an independent prognostic factor in patients with UC treated with radical cystectomy.
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http://dx.doi.org/10.1155/2019/6702964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732616PMC
February 2020

Clinical outcomes of muscle invasive bladder Cancer according to the BASQ classification.

BMC Cancer 2019 Sep 9;19(1):897. Epub 2019 Sep 9.

Department of Urology, Seoul National Univervity College of Medicine, Seoul National University Hospital, Seoul, Korea.

Background: We evaluated the clinical efficacy and prognosis of muscle-invasive bladder cancer according to the basal/squamous-like (BASQ) classification system based on immunohistochemical staining [CK5/6(+), CK14(+), GATA3(-), and FOXA1(-)].

Methods: One hundred patients diagnosed with muscle-invasive bladder cancer (cT2-4 N0-3 M0) were included in the study. All patients underwent radical cystectomy after transurethral removal of bladder tumor. Immunostaining was performed for CK5/6, CK14, FOXA1, and GATA3 antibodies on tissue microarray slides, and expression patterns were quantitatively analyzed using a scanning program.

Results: The median follow-up time was 77.4 (interquartile range: 39-120.9) months. The mean age of the patients was 65.1 ± 11.2 years. FOXA1 or CK14 expression greater than 1% was respectively positively and negatively correlated with overall survival (OS; p = 0.011 and p = 0.042, respectively), cancer-specific survival (CSS; p = 0.050 for both), and recurrence-free survival (RFS; p = 0.018 and p = 0.040, respectively). For CK5/6+ and GATA3- or FOXA1- expression, 10% CK5/6+ cells were negatively correlated with OS (p = 0.032 and p = 0.039, respectively) and with RFS in combination with FOXA1- only (p = 0.050).

Conclusions: In this study, CK14 expression was associated with a poor prognosis. The new classification system of bladder cancer based on molecular characteristics is expected to helpful tool for the establishment of personalized treatment strategies and associated prediction of therapeutic responses.
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http://dx.doi.org/10.1186/s12885-019-6042-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734465PMC
September 2019

Late Recurrence of Bladder Cancer following Radical Cystectomy: Characteristics and Outcomes.

Urol Int 2019 28;103(3):291-296. Epub 2019 Aug 28.

Department of Urology, Seoul National University Hospital, Seoul, Republic of Korea,

Purpose: There are only a few studies on characteristics and outcomes of late recurrence (LR) of urothelial carcinoma of bladder (UCB) after radical cystectomy (RC). The objective of this study was to assess characteristics and oncological outcomes of such LR that developed 5 years after RC.

Materials And Methods: We retrospectively reviewed 570 patients who underwent RC and bilateral regional lymphadenectomy for UCB at our institution. Comparisons of post-recurrence disease-specific survival (DSS) according to the timing of recurrence and the site of recurrence were performed using Kaplan-Meier survival curves and log-rank test. Cox regression model was fitted to assess factors for post-recurrence DSS.

Results: Disease recurrence occurred in 214 (37.5%) patients, including 20 (9.3%) who had LRs. Median time from RC to recurrence was 13.0 (interquartile range 6.0-32.0) months. There were no significant differences in clinicopathological factors between early- and late-recurrence groups. Post-recurrence 5-year DSS was not significantly different (21.6 vs. 14.1%, p = 0.344) between early- and late-recurrence groups. However, it was worse in the nonurothelial recurrence group compared to that in the urothelial recurrence group (14.0 vs. 19.4%, p = 0.056). Older age (HR 1.03, 95% CI 1.01-1.05, p = 0.001), nonorgan-confined disease at RC (HR 1.73, 95% CI 1.15-2.61, p = 0.008), and lymph node invasion (HR 1.58, 95% CI 1.01-2.45, p = 0.043) were significant predictors for post-recurrence 5-year DSS.

Conclusions: LR after RC with lymphadenectomy is not common. However, it cannot be overlooked. LR had similar characteristics to early recurrence. Interestingly, the time to recurrence did not affect post-recurrence survival.
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http://dx.doi.org/10.1159/000502656DOI Listing
February 2020

Second-Line Systemic Treatment for Metastatic Urothelial Carcinoma: A Network Meta-Analysis of Randomized Phase Clinical Trials.

Front Oncol 2019 25;9:679. Epub 2019 Jul 25.

Department of Urology, Seoul National University College of Medicine, Seoul, South Korea.

We aimed to evaluate and compare relative impacts of various second-line treatments on overall survival (OS) in metastatic urothelial carcinoma (mUC). A literature search was conducted in PubMed, Embase, and the Cochrane Library for all articles published prior to December 2018 in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. Seven randomized controlled trials with phase III design that met study eligibility criteria were selected for final analysis. A Bayesian framework network meta-analysis (NMA) was applied to indirectly compare the effect of each treatment on OS. In NMA, atezolizumab (HR, 0.90; 95% CI, 0.57-1.40) and pembrolizumab (HR, 0.77, 95% CI, 0.48-1.20) showed no significant effect on OS improvement compared to vinflunine. Gemcitabine/paclitaxel combination (HR, 1.30; 95% CI, 0.80-1.90) and lapatinib (HR, 0.95; 95% CI, 0.57-1.60) was not significantly associated with OS improvement compared to atezolizumab and best supportive care, respectively. However, results of rankograms revealed that pembrolizumab and atezolizumab were the first and second rank therapeutic agents for OS improvement in post-platinum mUC. Our NMA results are inconclusive. The optimal second-line treatment for OS improvement could not be determined because there were no significant OS differences among evaluated therapeutic agents. However, the use of immunotherapeutic agents such as atezolizumab and pembolizumab may have priority for improving OS in second-line setting of mUC.
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http://dx.doi.org/10.3389/fonc.2019.00679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669358PMC
July 2019

Intravesical Chemotherapy after Radical Nephroureterectomy for Primary Upper Tract Urothelial Carcinoma: A Systematic Review and Network Meta-Analysis.

J Clin Med 2019 Jul 19;8(7). Epub 2019 Jul 19.

Department of Urology, Seoul National University Hospital, Seoul 03080, Korea,.

The aim of this study was to determine the prophylactic effect of intravesical chemotherapy. Furthermore, it aimed to compare the efficacy of regimens on the prevention of bladder recurrence, after nephroureterectomy, for upper tract urothelial carcinoma by systematic review and network meta-analysis. A comprehensive literature search was conducted to search for studies published before 22 December 2016 using PubMed, Embase, and Scopus. All studies comparing nephroureterectomy alone with prophylactic intravesical chemotherapy after nephroureterectomy were included. The primary outcome was intravesical recurrence-free survival rate. In addition, we conducted indirect comparisons among regimens using network meta-analysis, as well as three randomized controlled trials (RCTs) on multicenter setting, and one large retrospective study with a total of 532 patients were analyzed. The pooled hazard ratio (HR) of bladder recurrence was 0.54 (95% CI: 0.38-0.76) in intravesical instillation patients. On network meta-analysis, pirarubicin was ranked the most effective regimen, while maintenance therapy of mitomycin C (MMC) with Ara-C and induction therapy of MMC were ranked as the second and third most effective regimens, respectively. Our study demonstrates that intravesical chemotherapy can prevent bladder recurrence in patients with upper tract urothelial carcinoma after nephroureterectomy. It also suggests that a single instillation of pirarubicin is the most efficacious intravesical regimen.
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http://dx.doi.org/10.3390/jcm8071059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678753PMC
July 2019

The facile and simple synthesis of poly(3,4ethylenedioxythiophene) anchored reduced graphene oxide nanocomposite for biochemical analysis.

Anal Chim Acta 2019 Oct 24;1077:150-159. Epub 2019 May 24.

Department of Energy and Materials Engineering, Dongguk University-Seoul, Seoul, 100-715, Republic of Korea. Electronic address:

In this article, we demonstrate the potentiostatic electrodeposition of poly(3,4-ethylenedioxythiophene) (PEDOT) on reduced graphene oxide (RGO) to develop a nanocomposite-modified electrode that separates three coexisting biofluids - ascorbic acid (AA), dopamine (DA), and uric acid (UA) - in a 0.1 M Phosphate buffer solution at a physiological pH (7.4). The texture, physicochemical properties, and electrochemical behavior of the PEDOT-RGO were explored using UV-visible spectroscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, electron microscopic techniques, and electrochemical impedance spectroscopy (EIS). A PEDOT-RGO/GCE was evaluated with respect to a bare GCE, RGO/GCE, and PEDOT/GCE for the simultaneous sensing of AA, DA, and UA. The difference in voltammetric peak potentials was about 180 mV between AA and DA and 120 mV between DA and UA. The differential pulse voltammetric sensor provided a linear calibration for a wide concentration range (0.1-907 μM for AA, 0.1-901 μM for DA, and 0.1-701 μM for UA) with detection limits of 1.5 μM, 0.6 μM, and 0.2 μM for AA, DA, and UA, respectively. The developed sensor was validated by the detection of AA, DA, and UA in a vitamin C tablet, a dopamine hydrochloride injection, and human serum samples.
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http://dx.doi.org/10.1016/j.aca.2019.05.053DOI Listing
October 2019

Establishment of the Seoul National University Prospectively Enrolled Registry for Genitourinary Cancer (SUPER-GUC): A prospective, multidisciplinary, bio-bank linked cohort and research platform.

Investig Clin Urol 2019 07 20;60(4):235-243. Epub 2019 May 20.

Department of Urology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

Purpose: To establish a prospective, comprehensive, multidisciplinary, bio-bank linked genitourinary cancer cohort based on standard real practice.

Materials And Methods: We established the Seoul National University Prospectively Enrolled Registry for Genitourinary Cancer (SUPER-GUC), a prospective cohort clinical database and bio-specimen repository system for prostate cancer (SUPER-PC), renal cell carcinoma (SUPER-RCC), and urothelial cancer (SUPER-UC) at a high-volume, tertiary institution. Each cohort consists of several sub-cohorts based on treatment or disease status. Detailed longitudinal clinical information, and general and disease specific patient-reported outcomes are captured. We use the same evaluation format and questionnaires for all participating departments. Patients' blood, urine, tumor, and normal tissues are collected. The number of registered patients and their basic characteristics are summarized. For the surgical sub-cohort, study participation, bio-specimen, and tissue banking rates are analyzed.

Results: Since March 2016, 11 sub-cohorts for all disease statuses have been opened, ranging from low-risk localized to metastatic disease. SUPER-PC, SUPER-RCC, and SUPER-UC enrolled 929, 796, and 1,221 patients, respectively. Study participation, bio-sampling, and fresh frozen tumor banking rates of surgical sub-cohorts were 89.0% to 93.1%, 91.2% to 99.1%, and 56.9% to 79.1%, respectively.

Conclusions: SUPER-GUC is a study platform for comparative outcome, quality-of-life, and translational (genetics, biomarkers) research for genitourinary cancer.
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http://dx.doi.org/10.4111/icu.2019.60.4.235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607078PMC
July 2019

Prostate specific antigen (PSA) persistence 6 weeks after radical prostatectomy and pelvic lymph node dissection as predictive factor of radiographic progression in node-positive prostate cancer patients.

J Cancer 2019 21;10(10):2237-2242. Epub 2019 May 21.

Department of Urology, Seoul National University Hospital, Seoul, Korea.

: To evaluate the prognostic value of early postoperative prostate specific antigen (PSA) levels after radical prostatectomy (RP) and pelvic lymph node dissection (PLND) in prostate cancer patients with lymph node invasion (LNI). : The retrospective analysis involved 96 patients who had a diagnosis of LNI with available data on the first PSA level at postoperative 6 weeks after RP and PLND between 2002 and 2014 at our institution. PSA persistence was defined as PSA ≥ 0.1 ng/ml at 6 weeks after surgery. Radiographic progression was defined as positive imaging during follow-up after the onset of biochemical recurrence, consisting of a bone scan and/or computed tomography (CT) and/or magnetic resonance imaging and/or 18F-(2-deoxy-2-fluoro-D-glucose positron emission tomography/CT scan. Comparative analysis of patients with and without PSA persistence was done, and Kaplan-Meier curve analysis with log-rank test and Cox proportional hazard regression models assessed radiographic progression free survival (PFS). : Fifty two (54.2%) patients displayed PSA persistence. Kaplan-Meier curve analysis showed significantly decreased 5-year radiographic PFS (64.2% vs. 93.2%, log-rank, p=0.009) in the PSA persistence group compared to the no PSA persistence group. In a multivariate analysis, PSA persistence was a statistically significant predictor of radiographic PFS. : Early assessment of PSA after surgery is important for predicting radiographic progression in node-positive prostate cancer patients. Risk stratification based on the early PSA value after surgery would be helpful to identify patients who may benefit from early adjuvant therapies.
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http://dx.doi.org/10.7150/jca.29714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584413PMC
May 2019

Korean version of the G-8 geriatric screening tool: Translation and linguistic validation.

J Geriatr Oncol 2020 04 22;11(3):470-474. Epub 2019 Jun 22.

Department of Urology, Seoul National University Hospital, 101 Daehak - ro, Jongno - gu, Seoul 110 -744, Republic of Korea. Electronic address:

Objective: To develop a Korean version of the G-8 questionnaire validated with Korean patients over 70 years-of-age who were scheduled to undergo cancer surgery.

Materials And Methods: We conducted a translation study over a nine-month period from February to November 2017. Permission was received to use the original version of the G-8 questionnaire for forward translation into Korean and reconciliation, for backward translation of the translated Korean version into English, for cognitive debriefing, and final proofreading. These steps were performed in the order of translation and then language validation. Forward translation was performed independently by two translators who were fluent in Korean and English. The cognitive debriefing was carried out through interviews with ten Korean nurses who cared for the patients surveyed.

Results: In the forward translation, "mobility" was replaced by "degree of activity". During the reconciliation, the difference in meaning between the terms "loss of appetite" and "severe," as determined by the two translators, was adjusted. Moreover, to achieve more natural Korean expression, some revisions were made to the questions and answers. In the backward translation, most of the forward translations were accepted without any objection. During the final proofreading, no difficulties were found in understanding the questionnaire's content, and most terms were deemed easy to understand.

Conclusion: This Korean version of the G-8 questionnaire has been validated in accordance with appropriate procedures. Therefore, the questionnaire is appropriate for use as a geriatric screening tool for older patients with cancer in Korea.
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http://dx.doi.org/10.1016/j.jgo.2019.06.002DOI Listing
April 2020

A Low Geriatric Nutritional Risk Index is Associated with Aggressive Pathologic Characteristics and Poor Survival after Nephrectomy in Clear Renal Cell Carcinoma: A Multicenter Retrospective Study.

Nutr Cancer 2020 1;72(1):88-97. Epub 2019 Jun 1.

Department of Urology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Korea.

To investigated the prognostic significance of the geriatric nutritional risk index (GNRI) in patients with surgically treated clear cell renal cell carcinoma (ccRCC). 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. 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. Malnutrition as assessed by the preoperative GNRI is associated with aggressive tumor characteristics and poor survival in patients with surgically treated ccRCC.
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http://dx.doi.org/10.1080/01635581.2019.1621357DOI Listing
September 2020

Establishment of Novel Intraoperative Monitoring and Mapping Method for the Cavernous Nerve During Robot-assisted Radical Prostatectomy: Results of the Phase I/II, First-in-human, Feasibility Study.

Eur Urol 2020 08 16;78(2):221-228. Epub 2019 May 16.

Department of Urology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address:

Background: Potency preservation often does not meet expectation despite nerve-sparing prostatectomy.

Objective: To set the protocol for intraoperative cavernous nerve monitoring and mapping during robot-assisted radical prostatectomy (RARP), and to evaluate its safety and clinical feasibility.

Design, Setting, And Participants: A prospective phase I/II, feasibility study was performed. A total of 30 patients with prostate cancer who underwent RARP at a high-volume tertiary academic hospital were enrolled.

Surgical Procedure: Pudendal somatosensory evoked potential, bulbocavernosus reflex, spontaneous corpus cavernosum electromyography (CC-EMG), median nerve stimulation evoked CC-EMG, and neurovascular bundle (NVB)-triggered CC-EMG with various stimulation protocols were assessed during conventional RARP under total intravenous anesthesia with controlled muscle relaxation.

Measurements: The primary endpoint was the completion rate of planned surgery and assessment. Adverse events, and erectile and urinary functions were evaluated within 1 yr. CC-EMGs were graded and correlated with functional outcomes.

Results And Limitations: The completion rate was 100%. Only one patient experienced adverse events, which were not related to study intervention. Grades of CC-EMGs including NVB-triggered CC-EMG before prostate removal were associated with baseline five-item International Index of Erectile Function (IIEF-5) score (grades 0-1, 4.6±2.7; grade 2, 13.2±6.8; grades 3-4, 16.6±5.9; p=0.003). Furthermore, grades of CC-EMGs including NVB-triggered CC-EMG after prostate removal were significantly associated with potency recovery (grade 0, 12.5%; grade 1, 0%; grade 2, 33.3%; grades 3-4, 100% at 12 mo; p=0.005) and postoperative IIEF-5 scores at all evaluation time points (grades 0-1, 2.6±2.8; grade 2, 4.3±5.8; grades 3-4, 15.7±11.0 at 12 mo; p=0.003).

Conclusions: We successfully established the protocol for safe intraoperative cavernous nerve monitoring and mapping using CC-EMG during RARP. Its grades were well correlated with erectile function.

Patient Summary: In this first-in-human feasibility study, we successfully established the protocol for safe intraoperative cavernous nerve monitoring and mapping method during robot-assisted radical prostatectomy. The results were significantly associated with erectile function. Evaluation of clinical efficacy to preserve potency seems worthy of further optimization and investigation in confirmatory clinical trials.
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http://dx.doi.org/10.1016/j.eururo.2019.04.042DOI Listing
August 2020

Trends in clinical, operative, and pathologic characteristics of surgically treated renal mass in a Korean center: A surgical series from 1988 through 2015.

Investig Clin Urol 2019 05 22;60(3):184-194. Epub 2019 Apr 22.

Department of Urology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Korea.

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.
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http://dx.doi.org/10.4111/icu.2019.60.3.184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6495035PMC
May 2019

Is Primary Androgen Deprivation Therapy a Suitable Option for Asian Patients With Prostate Cancer Compared With Radical Prostatectomy?

J Natl Compr Canc Netw 2019 05;17(5):441-449

Department of Urology, Seoul St. Mary's Hospital, College of Medicine, Seoul.

Background: We conducted a comparative survival analysis between primary androgen deprivation therapy (PADT) and radical prostatectomy (RP) based on nationwide Korean population data that included all patients with prostate cancer.

Materials And Methods: This study enrolled 4,538 patients with prostate cancer from the National Health Insurance Service (NHIS) database linked with Korean Central Cancer Registry data who were treated with PADT or RP between January 1, 2007, and December 31, 2014. Kaplan-Meier and multivariate survival analyses stratified by stage (localized and locally advanced) and age (<75 and ≥75 years) were performed using a Cox proportional hazards model to evaluate treatment effects.

Results: Among 18,403 patients from the NHIS database diagnosed with prostate cancer during the study period, 4,538 satisfied inclusion criteria and were included in the analyses. Of these, 3,136 and 1,402 patients underwent RP or received PADT, respectively. Risk of death was significantly increased for patients who received PADT compared with those who underwent RP in the propensity score-matched cohort. In subgroup analyses stratified by stage and age, in every subgroup, patients who received PADT had a significantly increased risk of death compared with those who underwent RP. In particular, a much greater risk was observed for patients with locally advanced prostate cancer.

Conclusions: Based on a nationwide survival analysis of nonmetastatic prostate cancer, this study provides valuable clinical implications that favor RP over PDAT for treatment of Asian populations. However, the possibility that survival differences have been overestimated due to not accounting for potential confounding characteristics must be considered.
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http://dx.doi.org/10.6004/jnccn.2018.7265DOI Listing
May 2019

Survival and clinical prognostic factors in metastatic non-clear cell renal cell carcinoma treated with targeted therapy: A multi-institutional, retrospective study using the Korean metastatic renal cell carcinoma registry.

Cancer Med 2019 07 9;8(7):3401-3410. Epub 2019 May 9.

Department of Urology, Center for Prostate Cancer, National Cancer Center, Goyang, Republic of Korea.

Objectives: The optimal treatment strategy for metastatic non-clear cell renal cell carcinoma (mNCCRCC) is still elusive and mainly extrapolated from evidence available for metastatic clear cell renal cell carcinoma. The aim of the study was therefore to investigate the survival outcomes and prognostic factors affecting survival in patients with mNCCRCC treated with targeted therapy.

Materials And Methods: We analyzed a total of 156 patients (8.1%) with mNCCRCC among the total cohort of 1922 patients in the Korean metastatic RCC registry. We used Kaplan-Meier curve analysis to calculate the survival estimates for first-line progression-free survival (PFS), total PFS, and cancer-specific survival (CSS). We also used the log-rank test to compare the different groups and multivariate Cox-proportional hazard regression analyses to evaluate the prognostic factors for survival.

Results: The mNCCRCC group had significantly inferior survival outcomes in terms of first-line PFS, total PFS, and CSS (all P < 0.05). We found survival benefits in patients treated with first-line vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKIs, first-line PFS, and total PFS, all P < 0.05), cytoreductive nephrectomy (CSS, P < 0.0001), metastasectomy (CSS, P = 0.0017), and patients with metachronous metastasis (first-line PFS, total PFS, and CSS, all P < 0.05). Liver metastasis was the only significant prognostic factor for both first-line PFS and CSS (all P < 0.05).

Conclusions: In the current targeted therapy era, survival of mNCCRCC is still inferior in comparison with that of mCCRCC patients. We found survival benefits in patients treated with first-line VEGF-TKIs/CN/metastasectomy, and metachronous metastasis patients.
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http://dx.doi.org/10.1002/cam4.2222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601573PMC
July 2019

Association Between Preoperative Hydronephrosis and Prognosis After Radical Cystectomy Among Patients With Bladder Cancer: A Systemic Review and Meta-Analysis.

Front Oncol 2019 19;9:158. Epub 2019 Mar 19.

Department of Urology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea.

Preoperative hydronephrosis (HN) might be associated with adverse outcomes in patients who underwent radical cystectomy (RC). The aim of this study was to evaluate the effect of preoperative HN on the oncological outcomes in patients with bladder cancer who underwent RC by performing a systemic review and meta-analysis. A systematic literature review in PubMed, EMBASE, and Scopus was conducted by searching the terms "bladder cancer," "cystectomy," and "hydronephrosis" until December 2016, in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. The calculated end points were advanced disease stage, cancer-specific survival (CSS), and overall survival (OS). Twenty-four studies involving 10,461 patients who underwent RC were included. Among the patients, 3,121 (29.8%) had preoperative HN. The pooled analysis showed that preoperative HN had a significant association with advanced stage (odds ratio, 2.56, 95% confidence interval [CI], 1.91-3.42, < 0.00001), lymph node invasion (OR, 2.44, 95% CI, 1.79-3.34, < 0.00001), CSS (hazard ratio [HR], 1.67, 95% CI, 1.34-2.08, < 0.00001), and OS (HR, 1.51, 95% CI, 1.30-1.75, < 0.00001). Among patients with bladder cancer who underwent RC, preoperative HN could be a significant predictor of bladder cancer survival. However, large well-designed prospective studies are required to confirm the precise prognostic significance of preoperative HN.
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http://dx.doi.org/10.3389/fonc.2019.00158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433994PMC
March 2019

Clinical outcomes and costs of robotic surgery in prostate cancer: a multiinstitutional study in Korea.

Prostate Int 2019 Mar 4;7(1):19-24. Epub 2018 May 4.

Department of Nursing Science, College of Nursing, Gachon University, Incheon, Korea.

Background: This study compared the surgical, functional, and oncologic outcomes of robot-assisted laparoscopic radical prostatectomy (RALP), laparoscopic radical prostatectomy (LRP), and retropubic radical prostatectomy (RRP) in Korean men.

Methods: The study population included 864 patients who underwent radical prostatectomy for prostate cancer in the departments of urology of five tertiary hospitals between 2010 and 2011. RALP, LRP, and RRP perioperative, oncological, and functional outcomes as well as complications were assessed. Medical cost data were analyzed for 682 of 864 patients.

Results: No significant differences were found among the three groups regarding the length of stay, biochemical recurrence, complications, and metastasis. The RALP group had a significantly higher rate of pelvic lymph node dissection (64.6% vs. 35.3% or 53.3%, <0.0001) and bilateral nerve-sparing procedures (15.7% vs. 10.0% or 8.9%, <0.0001) and less blood loss (median 250 mL vs. 300 mL or 700 mL, <0.0001) than the LRP and RRP groups. The 12-month continence recovery rate was higher in the RALP group (92.1%) than in the LRP (86.5%) and RRP (84.4%) groups ( <0.0001). Medical costs for RALP were approximately twofold to threefold higher than those for LRP or RRP.

Conclusions: Our findings suggest that surgical and functional outcomes are better with robot-assisted surgery than with laparoscopic or open surgery in terms of estimated blood loss and urinary continence; however, no differences were found among groups in terms of biochemical recurrence and the rate of complications.
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http://dx.doi.org/10.1016/j.prnil.2018.04.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6424675PMC
March 2019