Publications by authors named "Chang Wook Jeong"

257 Publications

Head to head comparison of Ga-NGUL and Ga-PSMA-11 in patients with metastatic prostate cancer: a prospective study.

J Nucl Med 2021 Feb 26. Epub 2021 Feb 26.

Seoul National University College of Medicine, Korea, Republic of.

Ga-NOTA Glu-Urea-Lys (NGUL) is a novel prostate-specific membrane antigen (PSMA) targeting tracer used for positron emission tomography/computed tomography (PET/CT) imaging. This study aims to compare the performance in the detection of primary and metastatic lesions, and to compare biodistribution between Ga-NGUL and Ga-PSMA-11 in the same patients with metastatic prostate cancer. Eleven patients with histologically proven, metastatic prostate cancer were prospectively recruited. Each patient underwent Ga-NGUL and Ga-PSMA-11 PET/CT within 4 days. The PET/CT scans were performed at 60 minutes after tracer injection. The quantitative tracer uptakes were obtained in normal organs including salivary glands, liver, spleen, and kidney and blood pool activity was measured in the inferior vena cava. The normal organ distribution of both tracers was quantified as SUVmean. In addition, three patients underwent dynamic PET/CT scanning (60 min) of the pelvic region to evaluate the urinary clearance. Any focal accumulation of Ga-NGUL and Ga-PSMA-11 not explained by physiologic uptake were defined as pathologic lesions. Lesion numbers and lesion uptake, as SUV, were compared. Quantitative uptakes in the kidneys, salivary glands, spleen, and liver were significantly lower on Ga-NGUL compared with Ga-PSMA-11. The blood pool activity showed no significant difference between the two tracers. The bladder time activity curve revealed a more rapid urinary clearance of Ga-NGUL. The number and sites of detected PSMA positive primary ( = 11) and metastatic lesions ( = 220) were identical between both tracers. Quantitative uptakes of primary tumors, lymph node, and bone metastases were well correlated (R2 = 0.869, 0.845, and 0.624, respectively) without significant difference ( = 0.675, 0.175, and 0.102, respectively) between Ga-NGUL and Ga-PSMA-11. Ga-NGUL showed a relatively lower tumor-to-background (gluteal muscle) ratio than Ga-PSMA-11, especially for bone metastasis. In head to head comparison with Ga-PSMA-11, Ga-NGUL showed lower uptake in normal organs and a trend of relatively low tumor-to-background ratio compared to Ga-PSMA-11. However, both tracers showed similar performance to detect PSMA avid primary and metastatic lesions without significant difference in the absolute lesion uptake. Ga-NGUL could be a valuable option for PSMA imaging and, furthermore, applied in theranostics.
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http://dx.doi.org/10.2967/jnumed.120.258434DOI Listing
February 2021

Prognostic significance of pathologic nodal positivity in non-metastatic patients with renal cell carcinoma who underwent radical or partial nephrectomy.

Sci Rep 2021 Feb 4;11(1):3079. Epub 2021 Feb 4.

Department of Urology, Center for Urologic Cancer, Research Institute and Hospital of National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10408, Republic of Korea.

This retrospective, five-multicenter study was aimed to evaluate the prognostic impact of pathologic nodal positivity on recurrence-free (RFS), metastasis-free (MFS), overall (OS), and cancer-specific (CSS) survivals in patients with non-metastatic renal cell carcinoma (nmRCC) who underwent either radical or partial nephrectomy with/without LN dissection. A total of 4236 nmRCC patients was enrolled between 2000 and 2012, and followed up through the end of 2017. Survival measures were compared between 52 (1.2%) stage pT1-4N1 (LN+) patients and 4184 (98.8%) stage pT1-4N0 (LN-) patients using Kaplan-Meier analysis with the log-rank test and Cox regression analysis to determine the prognostic risk factors for each survival measure. During the median 43.8-month follow-up, 410 (9.7%) recurrences, 141 (3.3%) metastases, and 351 (8.3%) deaths, including 212 (5.0%) cancer-specific deaths, were reported. The risk factor analyses showed that predictive factors for RFS, CSS, and OS were similar, whereas those of MFS were not. After adjusting for significant clinical factors affecting survival outcomes considering the hazard ratios (HR) of each group, the LN+ group, even those with low pT stage, had similar to or worse survival outcomes than the pT3N0 (LN-) group in multivariable analysis and had significantly more relationship with RFS than MFS. All survival measures were significantly worse in pT1-2N1 patients (MFS/RFS/OS/CSS; HR 4.12/HR 3.19/HR 4.41/HR 7.22) than in pT3-4N0 patients (HR 3.08/HR 2.92/HR 2.09/HR 3.73). Therefore, LN+ had an impact on survival outcomes worse than pT3-4N0 and significantly affected local recurrence rather than distant metastasis compared to LN- in nmRCC after radical or partial nephrectomy.
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http://dx.doi.org/10.1038/s41598-021-82750-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862313PMC
February 2021

Targeted therapy response in early versus late recurrence of renal cell carcinoma after surgical treatment: A propensity score-matched study using the Korean Renal Cancer Study Group database.

Int J Urol 2021 Feb 1. Epub 2021 Feb 1.

Department of Urology, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea.

Objectives: To investigate the clinicopathological features and outcomes of targeted therapy in patients with recurrence of renal cell carcinoma in <5 years or ≥5 years after the surgical treatment for renal cell carcinoma.

Methods: Patients with metastatic renal cell carcinoma treated with targeted therapy in a multicenter database were retrospectively characterized according to time from surgery to recurrence. Early recurrence was defined as recurrence within 5 years after surgery, and late recurrence was defined as occurring ≥5 years after surgery. The propensity scores for recurrence status were calculated, and patients with late recurrence were matched to patients with early recurrence at a 1:3 ratio. The oncological outcomes of targeted therapy in both groups were compared.

Results: Among 716 patients, 512 (71.5%) experienced early recurrence and 204 (28.5%) experienced late recurrence. The patients with late recurrence presented with younger age at surgery, lower tumor stages and Fuhrman grade, and fewer sarcomatoid features and lymphovascular invasion (all P < 0.005). All differences in clinicopathological characteristics before targeted therapy disappeared after matching. Patients with late recurrence had significantly longer median overall survival (56 months vs 36 months; P < 0.0001) and median first-line progression-free survival (12 months vs 8 months; P = 0.031). The early recurrence status was a significantly worse predictor for overall survival and first-line progression-free survival (hazard ratio 1.30, P = 0.007; and hazard ratio 1.76, P < 0.001, respectively).

Conclusions: Late recurrence might have prognostic value in terms of oncological outcomes in metastatic renal cell carcinoma treated with targeted therapy.
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http://dx.doi.org/10.1111/iju.14485DOI Listing
February 2021

Korean version of the convalescence and recovery evaluation: translation and linguistic validation.

Prostate Int 2020 Dec 27;8(4):158-166. Epub 2020 May 27.

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

Background: To develop a Korean version of the original English version of the convalescence and recovery evaluation (CARE) questionnaire. The linguistic validation of the CARE questionnaire was tested on Korean patients who underwent abdominal and pelvic surgery.

Methods: The CARE questionnaire was translated and validated linguistically in the following steps. Permission to translate the Korean version of the original version, forward translation into the Korean, reconciliation, backward translation into English, cognitive debriefing through patient interviews, and finally proofreading.

Results: The forward translation was carried out by two independent bilingual translators with non-medical backgrounds. In the translation step to Korean, the terms "bloated and gassy" and "trouble concentrating" were adjusted to make them easier to understand. Backward translation was performed by another translator who was not included in the forward translation. At the backward-translation stage, the Korean version was accepted without any objection, almost matching the original version except for a few words. Cognitive debriefing by means of patient interviews was performed with 10 patients admitted to the department of urology for renal, bladder, and prostate cancer for cancer treatment. There was no difficulty in understanding the content of the questionnaire. Because most of the terms were clear and understandable, no further changes were made in the panel discussion.

Conclusions: The Korean version of the CARE questionnaire has been verified and is ready for use. Additional testing steps are required for the psychometric performance of the Korean version of CARE.
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http://dx.doi.org/10.1016/j.prnil.2020.05.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767938PMC
December 2020

Regional Variation in Active Surveillance for Low-Risk Prostate Cancer in the US.

JAMA Netw Open 2020 12 1;3(12):e2031349. Epub 2020 Dec 1.

Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco.

Importance: Active surveillance (AS) is now recognized as the preferred management option for most low-risk prostate cancers to minimize risks of overtreatment. Despite increasing use of AS in the US, wide regional variability has been observed, and these regional variations in contemporary practice have not been well described.

Objective: To explore variations between county and Surveillance, Epidemiology, and End Results (SEER) regions in AS in the US.

Design, Setting, And Participants: A cohort study using the SEER Prostate with Watchful Waiting (WW) database linked to the County Area Health Resource File for detailed county-level demographics and physician distribution data was conducted from January 2010 to December 2015. Analysis was performed in October 2020. A total of 79 825 men with clinically localized, low-risk prostate cancer eligible for AS or WW were included.

Exposures: Multiple patient-, county-, and SEER region-level factors, including age, year of diagnosis, county-level densities of urologists, radiation oncologists, primary care physicians, and SEER registry region.

Main Outcomes And Measures: Use of AS or WW as the initial reported treatment strategy were noted. Hierarchical mixed-effect logistic regression models were used to evaluate clustered random regional variation on use of AS or WW. Temporal trends by year in proportions of initial treatment type, as well as county-level local variation, were also estimated.

Results: Of 79 825 men (mean [SD] age, 62.8 [7.6] years, 11 292 [14.1%] non-Hispanic Black, 7506 [9.4%] Hispanic) with low-risk prostate cancer, the mean annualized percent increase in AS rates from 2010 to 2015 ranged from 6.3% in New Mexico to 81.0% in New Jersey. Differences across SEER regions accounted for 17% of the total variation in AS. Increasing age (51-60 years: odds ratio [OR], 1.33; 95% CI, 1.21-1.46; 61-70 years: OR, 1.86; 95% CI, 1.70-2.04; 71-80 years: OR, 2.26; 95% CI, 2.05-2.50) was associated with greater odds of AS. Hispanic ethnicity (OR, 0.79; 95% CI, 0.74-0.85), T category (OR, 0.79; 95% CI, 0.73-0.84), and Medicaid enrollment (OR, 0.73; 95% CI, 0.66-0.81) were associated with lower odds of AS. Black race, county-level socioeconomic factors (household income, educational level, and city type), and specialist densities were not associated with AS use.

Conclusions And Relevance: In this US cohort study based on the SEER-WW database, although the use of AS increased, considerable practice variation appeared to be associated with geographic location, but use of AS was not associated with Black race, specialty professional density, or socioeconomic factors. This small area variation underlies the broader national trends in AS practice and may inform policies aimed at continuing to affect risk-appropriate care for men throughout the US.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.31349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770559PMC
December 2020

Quantitative analysis of renal arterial variations affecting the eligibility of catheter-based renal denervation using multi-detector computed tomography angiography.

Sci Rep 2020 11 12;10(1):19720. Epub 2020 Nov 12.

Department of Urology, Seoul National University Hospital, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Catheter-based renal denervation (RDN) was introduced to treat resistant hypertension. However, the reduction in blood pressure after the RDN was modest. Catheter-based RDN was performed only at main renal arteries, except for accessory and branch arteries due to the diameter being too small for the catheter to approach. Here, we retrospectively analyzed the anatomy of diverse renal arteries via 64-channel multi-detector computed tomography angiograms of 314 consecutive donors who underwent living donor nephrectomy from January 2012 to July 2017. Occurrence rates of one or more accessory renal arteries in donors were 25.3% and 19.4% on the left and right sides, respectively. Early branching rates before 25 mm from the aorta to the right and left renal arteries were 13.7% and 10.5%, respectively. Overall, 63.1% and 78.3% of donors had no accessory artery bilaterally and no branched renal artery, respectively. As a result, 47.1% had only main renal arteries without an accessory artery and early-branching artery. Approximately half of the donors had multiple small renal arteries bilaterally, for which catheter-based denervation may not be suitable. Thus, preoperative computed tomography angiography requires careful attention to patient selection, and there is a need for improved methods for denervation at various renal arteries.
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http://dx.doi.org/10.1038/s41598-020-76812-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665003PMC
November 2020

The Relative Impact of Urinary and Sexual Function vs Bother on Health Utility for Men With Prostate Cancer.

JNCI Cancer Spectr 2020 Oct 25;4(5):pkaa044. Epub 2020 May 25.

Diller Family Comprehensive Cancer Center, Department of Urology, University of California, San Francisco, CA, USA.

Function and bother are related but distinct aspects of health-related quality of life. The objective of this study was to compare quantitatively the relative impacts of function and bother in urinary, sexual, and bowel outcomes on health utility as a reflection of health-related quality of life in men with prostate cancer. Our analysis included participants in the Cancer of the Prostate Strategic Urologic Research Endeavor utility supplementary study, with a final cohort of 1617 men. Linear regression on the patients' function and bother summary scores (0-100) from the University of California, Los Angeles Prostate Cancer Index was performed to predict bias-corrected health utilities. Urinary and sexual bother were associated with each health utility, and their coefficients were 3.7 and 20.8 times greater, respectively, than those of the corresponding function. To our knowledge, our study provides the first quantitative and direct comparison of the impacts of function vs bother on health utility.
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http://dx.doi.org/10.1093/jncics/pkaa044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583149PMC
October 2020

Efficacy of neoadjuvant atezolizumab treatment in patients with advanced urothelial bladder cancer according to the BASQ classification: a study protocol for an open-label, two-cohort, phase II trial.

BMJ Open 2020 10 15;10(10):e035530. Epub 2020 Oct 15.

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

Introduction: Atezolizumab is a programmed death ligand-1 inhibitor for urothelial bladder cancer treatment. Atezolizumab has become the standard therapy for patients with urothelial bladder cancer who are not responding to cisplatin-based chemotherapy and is also used as a first-line treatment in cisplatin-ineligible patients. However, the efficacy of atezolizumab as a neoadjuvant chemotherapy for radical cystectomy has not yet been published and is still under study. This trial investigates the effectiveness of basal/squamous-like (BASQ) classification in the selection of an effective target group of patients with muscle-invasive bladder cancer (MIBC) for neoadjuvant atezolizumab treatment.

Methods And Analysis: This study is an open-label, two-cohort, phase II trial. It was designed to evaluate the efficacy of neoadjuvant atezolizumab treatment in patients with MIBC (T2-4N0M0) pathological responses after neoadjuvant chemotherapy and radical cystectomy. According to the molecular subtype characteristics of previous transurethral resection of the bladder specimens, patients are divided into two groups: luminal type (KRT5/6-KRT14-FOXA1+GATA3+) and basal type (KRT5/6+KRT14+FOXA1-GATA3-). Every 3 weeks, atezolizumab is administered at a dose of 1200 mg for three cycles prior to radical cystectomy in patients with MIBC. The primary end point is objective pathological responses in the intention-to-treat patients. The secondary end point is a 1-year progression-free survival difference according to the BASQ classification in patients who underwent neoadjuvant atezolizumab treatment.

Ethics And Dissemination: The study protocol was approved by the Institutional Review Board of Seoul National University Hospital, Seoul, Republic of Korea (H 1806-051-950). The trial is registered at ClinicalTrials.gov. The trial results will be published in peer-reviewed journals and at conferences.

Trial Registration Number: NCT03577132.
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http://dx.doi.org/10.1136/bmjopen-2019-035530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566723PMC
October 2020

MLL5, a histone modifying enzyme, regulates androgen receptor activity in prostate cancer cells by recruiting co-regulators, HCF1 and SET1.

BMB Rep 2020 Dec;53(12):634-639

Department of Urology, Seoul National University Hospital, Seoul 03080, Korea; Department of Urology, Seoul National University College of Medicine, Seoul 03080, Korea.

In prostate cancer, the androgen receptor (AR) transcription factor is a major regulator of cell proliferation and metastasis. To identify new AR regulators, we focused on Mixed lineage leukemia 5 (MLL5), a histone-regulating enzyme, because significantly higher MLL5 expression was detected in prostate cancer tissues than in matching normal tissues. When we expressed shRNAs targeting MLL5 gene in prostate cancer cell line, the growth rate and AR activity were reduced compared to those in control cells, and migration ability of the knockdown cells was reduced significantly. To determine the molecular mechanisms of MLL5 on AR activity, we proved that AR physically interacted with MLL5 and other co-factors, including SET-1 and HCF-1, using an immunoprecipitation method. The chromatin immunoprecipitation analysis showed reduced binding of MLL5, co-factors, and AR enzymes to AR target gene promoters in MLL5 shRNA-expressing cells. Histone H3K4 methylation on the AR target gene promoters was reduced, and H3K9 methylation at the same site was increased in MLL5 knockdown cells. Finally, xenograft tumor formation revealed that reduction of MLL5 in prostate cancer cells retarded tumor growth. Our results thus demonstrate the important role of MLL5 as a new epigenetic regulator of AR in prostate cancer. [BMB Reports 2020; 53(12): 634-639].
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781910PMC
December 2020

Metastatic renal cell carcinoma to the pancreas: Clinical features and treatment outcome.

J Surg Oncol 2021 Jan 12;123(1):204-213. Epub 2020 Oct 12.

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

Background And Objectives: Metastatic renal cell carcinoma to the pancreas (PM-RCC) is infrequent; we sought to describe the characteristics of PM-RCC and analyze the outcome following treatment.

Methods: Data of 3107 mRCC patients treated between 1992 and 2007 from the Korean Renal Cancer Study Group database were obtained to identify 300 (9.7%) PM-RCC patients. Characteristics and survival were analyzed and compared to the rest of the mRCC, according to the timing of metastasis and surgical treatments received.

Results: PM-RCC was younger at initial diagnosis (55.0 vs. 58.2 years), more frequently in women (30.3% vs. 22.3%), and metachronous (65.3% vs. 41.9%) with a longer disease-free period (82.0 vs. 33.0 months). Overall survival (OS) was significantly better in PM-RCC but pancreas metastasectomy was associated with improved OS only among metachronous PM-RCC. In the 132 metachronous PM-RCC with pancreas metastasectomy, median recurrence-free survival was 17.2 months and we found Heng risk group (hazard ratio [HR] = 2.384, 95% confidence interval [CI] = 1.213-4.684), younger age (HR = 0.965, 95% CI = 0.945-0.987), shorter interval to pancreas metastasis (HR = 0.993, 95% CI = 0.986-0.999), and Eastern Cooperative Oncology Group performance status to be predictive of early progression following pancreas metastasectomy.

Conclusion: Compared to the other mRCC, PM-RCC demonstrated a favorable prognosis. Pancreas metastasectomy was associated with prolonged survival in the metachronous PM-RCC with a long progression-free period.
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http://dx.doi.org/10.1002/jso.26251DOI Listing
January 2021

Scale-Up Evaluation of a Composite Tumor Marker Assay for the Early Detection of Renal Cell Carcinoma.

Diagnostics (Basel) 2020 Sep 25;10(10). Epub 2020 Sep 25.

Department of Pathology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea.

The early detection of renal cell carcinoma (RCC) using tumor markers remains an attractive prospect for the potential to downstage the disease. To validate the scale-up clinical performance of potential tumor markers for RCC (as a single marker and as a composite tumor marker composed of nicotinamide N-methyltransferase (NNMT), L-Plastin (LCP1), and non-metastatic cells 1 protein (NM23A)), the scale-up assay was performed. Patients with RCC from multiple domestic institutes were included in the clinical evaluation for reassessment and improvement of the established triple markers of our product. For the diagnostic performance of the composite markers, the best-split cutoff points of each marker (147 pg/mL for NNMT, 1780 pg/mL for LCP1, and 520 pg/mL for NM23A) were installed. Serum levels of NNMT, LCP1, and NM23A were greatly increased in subjects with RCC ( < 0.0001). In 1042 blind sample tests with control individuals (n = 500) and patients with RCC (n = 542), the diagnostic sensitivity and specificity of the composite three-marker assay were 0.871 and 0.894, respectively, and the resulting AUC (Area under Curve) of ROC (Receiver Operating Characteristic) was 0.917. As a single marker, the diagnostic accuracies of NNMT, LCP1, and NM23A, as estimated by ROC, were 0.833, 0.844, and 0.601, respectively. The composite three-marker assay with NNMT, LCP1, and NM23A is a more improved novel serum marker assay for the early detection of RCC in cases of renal mass or unknown condition. The NNMT, LCP1, and NM23A triple marker assay could be a powerful diagnostic tumor marker assay to screen the early stage of RCC.
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http://dx.doi.org/10.3390/diagnostics10100750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601868PMC
September 2020

RNA-Seq profiling of microdissected glomeruli identifies potential biomarkers for human IgA nephropathy.

Am J Physiol Renal Physiol 2020 11 21;319(5):F809-F821. Epub 2020 Sep 21.

Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.

Few studies have examined gene expression changes occurring in the glomeruli of IgA nephropathy (IgAN) using a sensitive transcriptomic profiling method such as RNA sequencing (RNA-Seq). We collected glomeruli from biopsy specimens from patients with IgAN with relatively preserved kidney function (estimated glomerular filtration rate ≥ 60 mL·min·1.73 m and urine protein-to-creatinine ratio < 3 g/g) and from normal kidney cortexes by hand microdissection and performed RNA-Seq. Differentially expressed genes were identified, and gene ontology term annotation and pathway analysis were performed. Immunohistochemical labeling and primary mesangial cell cultures were performed to confirm the findings of RNA-Seq analysis. Fourteen patients with IgAN and ten controls were included in this study. Glomerulus-specific genes were highly abundant. Principal component analysis showed clear separation between the IgAN and control groups. There were 2,497 differentially expressed genes, of which 1,380 were upregulated and 1,117 were downregulated (false discovery rate < 0.01). The enriched gene ontology terms included motility/migration, protein/vesicle transport, and immune system, and kinase binding was the molecular function overrepresented in IgAN. B cell signaling, chemokine signal transduction, and Fcγ receptor-mediated phagocytosis were the canonical pathways overrepresented. In vitro experiments confirmed that spleen tyrosine kinase (SYK), reported as upregulated in the IgAN transcriptome, was also upregulated in glomeruli from an independent set of patients with IgAN and that treatment with patient-derived IgA1 increased the expression of SYK in mesangial cells. In conclusion, transcriptomic profiling of the IgAN glomerulus provides insights in the intraglomerular pathophysiology of IgAN before it reaches profound kidney dysfunction. SYK may have a pathogenetic role in IgAN.
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http://dx.doi.org/10.1152/ajprenal.00037.2020DOI Listing
November 2020

The effect of preoperative ureteral stenting in retrograde Intrarenal surgery: a multicenter, propensity score-matched study.

BMC Urol 2020 Sep 14;20(1):147. Epub 2020 Sep 14.

Department of Urology, Seoul National University Hospital, 101 Daehak - ro, Jongno - gu, Seoul, 03080, Republic of Korea.

Background: Stent placement before retrograde intrarenal surgery (RIRS) can theoretically expand the ureter to improve access and remove stones. The purpose of this study was to investigate the effect of preoperative ureteral stenting on access and surgery.

Methods: We retrospectively analyzed patients who underwent RIRS between January 2010 and December 2016 at multiple centers. The patients were divided into two groups based on whether or not a ureteral stent was inserted preoperatively. The characteristics of the stone (size, number, density, and location), the success rate of the access sheath placement, perioperative complications, operative times, hospitalization periods, the period for which the stents remained, postoperative urinary tract infection rates, stone-free rates, and additional treatment rates were analyzed.

Results: Overall, 727 patients were included in the study (113 were pre-stented and 614 were non-stented). The median stone size was 12.2 mm. The overall stone-free rate (SFR) was 85.8% for the pre-stented group and 83.2% for the non-stented group, showing no significant (p = 0.498) difference between the two groups. Preoperative ureteral stenting improved the success rate of sheath placement (93.8% vs. 85.3%, p = 0.023) during surgery. The access sheath size in participants in the pre-stented group showed a tendency to be larger than that in participants in the non-stented group. However, there were no differences in perioperative complications, operative times, additional treatment rates, and stone-free rates.

Conclusions: Although preoperative ureteral stenting did not affect operative outcomes, it increased the success rate of access sheath placement. Depending on the patient's characteristics, preoperative ureteral stenting can be considered as an adjunctive option when access sheath insertion is considered during RIRS.
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http://dx.doi.org/10.1186/s12894-020-00715-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490880PMC
September 2020

Glue Embolization of Lymphopseudoaneurysm for Chylous Ascites after Retroperitoneal Surgery.

Korean J Radiol 2021 Mar 28;22(3):376-383. Epub 2020 Aug 28.

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

Objective: To assess the safety and efficacy of lymphopseudoaneurysm (LPA) glue (n-butyl cyanoacrylate [NBCA]) embolization in the management of chylous ascites after retroperitoneal surgery.

Materials And Methods: A retrospective analysis from January 2014 to October 2018 was performed in six patients (4 females and 2 males; mean age, 45.3 ± 14.2 years; range, 26-61 years) who underwent LPA embolization for chylous ascites developing after retroperitoneal surgery involving the perirenal space (four donor nephrectomies, one partial nephrectomy, and one retroperitoneal lymphadenectomy). After placing a percutaneous drainage catheter into the LPA or adjacent lymphocele, embolization was performed by filling the LPA itself with a mixture of glue and Lipiodol (Guerbet).

Results: Daily drainage from percutaneously placed drains exceeded 300 mL/day despite medical and surgical treatment (volume: mean, 1173 ± 1098 mL; range, 305-2800 mL). Intranodal lymphangiography was performed in four of the six patients and revealed leakage in 2 patients. Percutaneous embolization of the LPA was successful in all patients using an NBCA and Lipiodol mixture in a ratio of 1:1-1:2 (volume: mean, 4.3 ± 1.1 mL; range, 3-6 mL). Chylous ascites was resolved and the drainage catheter was removed in all patients within 4 days after the procedure (mean, 2.0 ± 1.8 days; range, 0-4 days). No procedure-related complications or recurrence of chylous ascites occurred during a mean follow-up period of 37.3 months (range, 21.1-48.4 months).

Conclusion: Glue embolization of LPA has the potential to be a feasible and effective treatment method for the management of chylous ascites after retroperitoneal surgery.
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http://dx.doi.org/10.3348/kjr.2020.0056DOI Listing
March 2021

Role of multiparametric magnetic resonance imaging to predict postoperative Gleason score upgrading in prostate cancer with Gleason score 3 + 4.

World J Urol 2020 Aug 31. Epub 2020 Aug 31.

Department of Urology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea.

Background: To evaluate the role of multiparametric magnetic resonance imaging (mpMRI) in Gleason score (GS) 3 + 4 prostate cancer (PCa) and evaluate independent factors in mpMRI that can predict GS upgrading, we compared the outcomes of GS upgrading group and GS non-upgrading group.

Patients And Methods: We analyzed the data of 539 patients undergoing radical prostatectomy (RP) for biopsy GS 3 + 4 PCa from two tertiary referral centers. Univariate and multivariate analyses were performed to determine significant predictors of GS upgrading. GS upgrading, the study outcome, was defined as GS ≥ 4 + 3 at definitive pathology at RP specimen.

Results: GS upgrading rate was 35.3% and biochemical recurrence (BCR) rate was 8.0%. GS upgrading group was significantly older (p = 0.015), had significantly higher prebiopsy serum prostate-specific antigen (PSA) level (p = 0.001) and PSA density (p = 0.003), had a higher number of prostate biopsy (p = 0.026). There were 413 lesions (76.6%) of PI-RADS lesion ≥ 4, 236 (57.1%) for PI-RADS 4 and 177 (42.9%) for PI-RADS 5 lesion. Multivariate logistic regression analysis revealed that age (p = 0.045), initial prebiopsy PSA level (p = 0.002) and presence of PI-RADS lesion ≥ 4 (p = 0.044) are independent predictors of GS upgrading.

Conclusion: MpMRI can predict postoperative Gleason score upgrading in prostate cancer with Gleason score 3 + 4. Especially, presence of clinically significant PI-RADS lesion ≥ 4, the significant predictor of GS upgrading, in preoperative mpMRI needs to be paid attention and can be helpful for patient counseling on prostate cancer treatment.
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http://dx.doi.org/10.1007/s00345-020-03421-7DOI Listing
August 2020

Histone Demethylase LSD1 Regulates Kidney Cancer Progression by Modulating Androgen Receptor Activity.

Int J Mol Sci 2020 Aug 24;21(17). Epub 2020 Aug 24.

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

Kidney cancer is one of the most difficult cancers to treat by targeted and radiation therapy. Therefore, identifying key regulators in this cancer is especially important for finding new drugs. We focused on androgen receptor (AR) regulation by its epigenetic co-regulator lysine-specific histone demethylase 1 (LSD1) in kidney cancer development. LSD1 knock-down in kidney cancer cells decreased expression of AR target genes. Moreover, the binding of AR to target gene promoters was reduced and histone methylation status was changed in LSD1 knock-down kidney cancer cells. LSD1 knock-down also slowed growth and decreased the migration ability of kidney cancer cells. We found that pargyline, known as a LSD1 inhibitor, can reduce AR activity in kidney cancer cells. The treatment of kidney cancer cells with pargyline delayed growth and repressed epithelial-mesenchymal transition (EMT) markers. These effects were additively enhanced by co-treatment with the AR inhibitor enzalutamide. Down-regulation of LSD1 in renal cancer cells (RCC) attenuated in vivo tumor growth in a xenograft mouse model. These results provide evidence that LSD1 can regulate kidney cancer cell growth epigenetic control of AR transcription factors and that LSD1 inhibitors may be good candidate drugs for treating kidney cancer.
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http://dx.doi.org/10.3390/ijms21176089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503698PMC
August 2020

Sharing the initial experience of pan-cancer panel analysis in high-risk renal cell carcinoma in the Korean population.

BMC Urol 2020 Aug 18;20(1):125. Epub 2020 Aug 18.

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

Background: This study aimed to assess the feasibility of a pan-cancer panel assay for high-risk renal cell carcinoma (RCC) in the Korean population. We also analyzed the clinical and genetic factors contributing to metastasis in clear cell RCC.

Methods: Thirty-one patients with advanced RCC who underwent radical nephrectomy were analyzed. A 1.8 Mb multi-cancer panel (including 25 RCC-related genes, such as VHL, PBRM1, SETD2, and MET), comprising 181 target genes, 23 fusion genes, and 45 drug target lesions developed by Seoul National University Hospital, was used for this study.

Results: We extracted DNA from 30 of the 31 (96.7%) RCC specimens. Twenty-one patients (average age 63.3 ± 11.3 years) with clear cell RCC, 5 with papillary RCC, 3 with chromophobe RCC, and one patient, each with MiT family translocation carcinoma RCC and succinate dehydrogenase deficiency RCC, were analyzed. The sequencing depth was 430.8 ± 206.6 and 97 mutations (7.3 ± 2.7 mutations per patient) were detected. The most commonly mutated genes were VHL (46%), PBRM1 (30%), and BAP1, NOTCH4, and POLQ (23.33% each). Compared with TNM stage matched data from TCGA of clear cell RCC, VHL and PBRM1 are most common in both cohorts. Univariate and multivariate analyses revealed that tumor size (Hazard ratio = 2.47, p = 0.04) and PBRM1 (Hazard ratio = 28.69, p = 0.05) were related to metastasis in clear cell RCC.

Conclusion: The pan-cancer panel comprised of RCC-related genes is a feasible and promising tool to evaluate genetic alterations in advanced RCC. However, large-scale studies and a focus on the clinical utility of this cancer panels is needed.
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http://dx.doi.org/10.1186/s12894-020-00687-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433120PMC
August 2020

Histone Demethylase KDM7A Regulates Androgen Receptor Activity, and Its Chemical Inhibitor TC-E 5002 Overcomes Cisplatin-Resistance in Bladder Cancer Cells.

Int J Mol Sci 2020 Aug 6;21(16). Epub 2020 Aug 6.

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

Histone demethylase KDM7A regulates many biological processes, including differentiation, development, and the growth of several cancer cells. Here, we have focused on the role of KDM7A in bladder cancer cells, especially under drug-resistant conditions. When the gene was knocked down, bladder cancer cell lines showed impaired cell growth, increased cell death, and reduced rates of cell migration. Biochemical studies revealed that KDM7A knockdown in the bladder cancer cells repressed the activity of androgen receptor (AR) through epigenetic regulation. When we developed a cisplatin-resistant bladder cancer cell line, we found that AR expression was highly elevated. Upon treatment with TC-E 5002, a chemical inhibitor of KDM7A, the cisplatin-resistant bladder cancer cells, showed decreased cell proliferation. In the mouse xenograft model, KDM7A knockdown or treatment with its inhibitor reduced the growth of the bladder tumor. We also observed the upregulation of KDM7A expression in patients with bladder cancer. The findings suggest that histone demethylase KDM7A mediates the growth of bladder cancer. Moreover, our findings highlight the therapeutic potential of the KMD7A inhibitor, TC-E 5002, in patients with cisplatin-resistant bladder cancer.
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http://dx.doi.org/10.3390/ijms21165658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460860PMC
August 2020

The platelet-to-lymphocyte ratio as a significant prognostic factor to predict survival outcomes in patients with synchronous metastatic renal cell carcinoma.

Investig Clin Urol 2020 09 23;61(5):475-481. Epub 2020 Jul 23.

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

Purpose: The clinical impact of the platelet-to-lymphocyte ratio (PLR) on the prognosis of patients with metastatic renal cell carcinoma (mRCC) remains controversial. We investigated the associations between elevation of the PLR and disease prognosis in patients with synchronous mRCC.

Materials And Methods: The data of 1,505 patients with synchronous mRCC were retrospectively analyzed. The entire cohort was stratified into two subgroups according to PLR. Kaplan-Meier and Cox proportional analyses were performed to investigate the possible associations between the PLR and disease prognosis.

Results: There were 921 patients with a high PLR and 584 patients with a low PLR by use of the cutoff of 146. The patients with a high PLR had worse clinical characteristics in terms of advanced clinical stage (p<0.001) and rate of lymph node invasion (p=0.036). The Kaplan-Meier analysis showed that patients with a high PLR had significantly shorter overall survival (OS) (p<0.001) and cancer-specific survival (CSS) (p<0.001). The multivariate Cox analysis revealed that the PLR was an independent predictor for shorter OS (hazard ratio [HR], 1.345; 95% confidence interval [CI], 1.183-1.530; p<0.001) and CSS (HR, 1.318; 95% CI, 1.156-1.502; p<0.001). In the subgroup analyses, the PLR showed a significant association with survival outcomes in the subgroup with clear cell type (all p<0.05) but not in the subgroup with the non-clear cell type.

Conclusions: The PLR was an independent prognostic factor for survival outcomes in patients with mRCC. However, the association was statistically significant only in patients with clear cell type mRCC.
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http://dx.doi.org/10.4111/icu.20200002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458873PMC
September 2020

Fumarate modulates phospholipase A2 receptor autoimmunity-induced podocyte injury in membranous nephropathy.

Kidney Int 2021 02 23;99(2):443-455. Epub 2020 Jul 23.

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

Downstream mechanisms that lead to podocyte injury following phospholipase A2 receptor (PLA2R) autoimmunity remain elusive. To help define this we compared urinary metabolomic profiles of patients with PLA2R-associated membranous nephropathy (MN) at the time of kidney biopsy with those of patients with minimal change disease (MCD) and to healthy individuals. Among the metabolites differentially expressed in patients with PLA2R-associated MN compared to healthy individuals, fumarate was the only significant differentially expressed metabolite in PLA2R-associated MN compared to MCD [fold-difference vs. healthy controls and vs. MCD: 1.76 and 1.60, respectively]. High urinary fumarate levels could predict the composite outcome of PLA2R-associated MN. Fumarate hydratase, which hydrolyzes fumarate, colocalized with podocalyxin, and its expression was lower in glomerular sections from patients with PLA2R-associated MN than in those from healthy individuals, patients with non-PLA2R-associated MN or MCD. Podocytes stimulated with IgG purified from serum with a high anti-PLA2R titer (MN-IgG) decreased expression of fumarate hydratase and increased fumarate levels. These changes were coupled to alterations in the expression of molecules involved in the phenotypic profile of podocytes (WT1, ZO-1, Snail, and fibronectin), an increase in albumin flux across the podocyte layer and the production of reactive oxygen species in podocytes. However, overexpression of fumarate hydratase ameliorated these alterations. Furthermore, knockdown of fumarate hydratase exhibited synergistic effects with MN-IgG treatment. Thus, fumarate may promote changes in the phenotypic profiles of podocytes after the development of PLA2R autoimmunity. These findings suggest that fumarate could serve as a potential target for the treatment of PLA2R-associated MN.
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http://dx.doi.org/10.1016/j.kint.2020.06.031DOI Listing
February 2021

Survival benefit of neoadjuvant chemotherapy in pathologic T2N0 or lower urothelial carcinoma patients: evidence to support the use of neoadjuvant chemotherapy.

Transl Androl Urol 2020 Jun;9(3):1270-1277

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

Background: To evaluate the survival benefit of neoadjuvant chemotherapy (NAC) in pathologic T2N0 or less patients.

Methods: A total of 526 patients with less than pT2N0 underwent radical cystectomy. Patients were divided into three groups: non-NAC, those who did not receive NAC; partial NAC, those who received less 3 cycles of NAC; and complete NAC, those who received 3 cycles of NAC.

Results: Median follow up was 74.6 (range, 24-311) months. Recurrent-free survival (RFS) was significantly (P=0.041) higher in the non-NAC group than that in the complete NAC group. Overall survival (OS) was significantly (P=0.039) higher in the non-NAC group than that in the complete NAC group. There was no significant difference between the partial NAC group and the complete NAC group. In patients with pT0, the NAC group had higher pT0 ratio than the non-NAC group (33.3% 21.1%). A total of 66.6% of NAC patients were down-staged to less than T2. In univariate and multivariate analyses, recurrence was significantly related to pathologic T stage (P<0.001), concurrent carcinoma (CIS) (P=0.002), and the number of removed lymph nodes (LNs) (P=0.001). Survival was significantly related to pathologic T stage (P<0.001), lymphovascular invasion (LVI) (P=0.002), the number of removed LNs (P<0.001), and the presence of NAC (P=0.047).

Conclusions: Patients with pT2 or lower underwent NAC showed similar prognosis as patients with pT2 or lower who did not undergo NAC.
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http://dx.doi.org/10.21037/tau-19-705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354338PMC
June 2020

Impact of short warm ischemic time on longitudinal kidney function and survival rate after partial nephrectomy for renal cell carcinoma in patients with pre-existing chronic kidney disease stage III: A multi-institutional propensity score-matched study.

Eur J Surg Oncol 2021 Feb 17;47(2):470-476. Epub 2020 Jun 17.

Department of Urology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea. Electronic address:

Purpose: It remains unclear whether a short warm ischemic time (WIT) improves long-term renal function after partial nephrectomy (PN) for patients with pre-existing chronic kidney disease (CKD). We evaluated renal function after PN according to WIT duration in patients with stage III CKD.

Materials And Methods: We identified 277 patients with stage III CKD who underwent PN during 2004-2017. Propensity score matching was used to created two matched groups of patients: Group A (WIT of <25 min) and Group B (WIT of ≥25 min). The outcomes of interest were longitudinal kidney function change, new-onset stage IV CKD (eGFR <30 mL/min/1.73 m) and overall survival.

Results: The two matched groups contained 85 patients each. The median follow-up durations were 49 months in Group A and 42 months in Group B. The median pre-treatment eGFRs were 52.4 mL/min/1.73 m in Group A and 52.6 mL/min/1.73 m in Group B. There were no differences in kidney function between the two groups throughout the follow-up period (P > 0.05). The 5-year rates of new-onset stage IV CKD were not significantly different between Group A and Group B (8.2% vs. 7.1%), with no significant difference in the risk of developing stage IV CKD in Group A (vs. group B, hazard ratio: 0.527, 95% confidence interval: 0.183-1.521; P = 0.236). The 5-year overall survival rates were 90.3% for Group A and 96.2% for Group B (P = 0.549).

Conclusions: A short WIT was not associated with better postoperative kidney function or survival after PN in patients with stage III CKD.
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http://dx.doi.org/10.1016/j.ejso.2020.06.016DOI Listing
February 2021

Differences in risk factors for biochemical recurrence after radical prostatectomy stratified by the degree of obesity: Focused on surgical methods.

Sci Rep 2020 06 23;10(1):10157. Epub 2020 Jun 23.

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

This study aims to evaluate differences in the risk factors for biochemical recurrence (BCR) for radical prostatectomy stratified by degree of obesity, focusing on the surgical method used. All 3099 patients who underwent radical prostatectomy in two medical centres from January 2008 to March 2018 were retrospectively reviewed. Patients were divided into three groups based on body mass index: 'normal', 'overweight', and 'obese'. Risk factors associated with biochemical recurrence were compared between different degrees of obesity. We analysed the contributing risk factors of BCR-free survival using univariate and multivariable Cox hazard models. There were 378 (12.2%) and 1815 (58.6%) patients in the 'obese' and 'overweight' groups, respectively. Accordingly, 1324 patients underwent retropubic radical prostatectomy (RRP), and 1775 underwent robotic-assisted laparoscopic prostatectomy (RALP). Multivariable analysis showed that patients who underwent RALP had significantly lower BCR free survival in the 'overweight' and 'obese' groups than those who underwent RRP, with adjusted hazard ratios of 0.75 (95% CI 0.59-0.95, p-value = 0.01) and 0.55 (95% CI 0.33-0.90, p-value = 0.02), respectively. The degree of obesity was not directly associated with BCR-free survival. Robotic prostatectomy showed greater benefits in BCR-free survival than open prostatectomy in the 'overweight' and 'obese' groups.
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http://dx.doi.org/10.1038/s41598-020-67237-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311457PMC
June 2020

Survival Benefits Based on the Number of Lymph Nodes Removed during Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: Systematic Review and Meta-Analysis.

J Clin Med 2020 Jun 21;9(6). Epub 2020 Jun 21.

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

The role of lymph node dissection (LND) is still controversial for upper tract urothelial carcinoma (UTUC), and there are no guidelines regarding its use. This study was conducted to find a higher level of evidence for the survival benefits based on the number of LNs removed during radical nephroureterectomy (RNUx) through a systematic review and meta-analysis. We included studies comparing patients who underwent LND during RNUx for UTUC. We searched the major electronic databases (Pubmed, Embase, and Scopus) and conducted manual searches of the electronically available abstracts of the major international urology cancer meetings [American Society of Clinical Oncology (ASCO), American Urological Association (AUA), and Eropean Association of Urology (EAU)] prior to April 2019 using grouped terms of nephroureterectomy (nephroureterectom*) and lymph node excision (lymphadenectomy; lymph + node*; lymph* + metasta*) with variations in the terms. Study selection, data collection, and risk of bias assessment were performed by two independent authors (A and B). Six retrospective case-control studies included a total of 33,944 patients who underwent RNUx for UTUC, 5071 of whom underwent LND and were finally included in the meta-analysis. The pooled hazard ratio (HR) in these studies revealed that an increased number of LNs removed during RNUx was associated with improved cancer-specific survival (CSS) in patients with UTUC (HR = 0.95, 95% CI: 0.91-0.99; = 0.07). In addition, increased numbers of LNs removed were associated with improved overall survival (OS) in pN0 patients. However, in pN+ patients, the number of LNs removed showed no survival benefit on CSS, overall survival (OS), or progression-free survival (PFS). Higher numbers of LNs removed during RNUx were associated with improved survival outcomes in patients with UTUC. This study confirmed that LND also has oncological benefits in UTUC patients. Although still a controversial topic, meticulous LND must be considered, and efforts should be made to eliminate as many LNs as possible when administering RNUx for UTUC, especially in patients without clear evidence of LN metastasis.
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http://dx.doi.org/10.3390/jcm9061933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357082PMC
June 2020

Development of a nitinol-actuated surgical instrument for laparoscopic renal denervation: feasibility test in a swine survival model.

Int J Hyperthermia 2020 ;37(1):573-584

Department of Creative IT Engineering, POSTECH, Pohang, Republic of Korea.

In this study, we developed a novel nitinol-actuated surgical instrument to conduct laparoscopic renal denervation for the treatment of resistant hypertension. We investigated whether shape and temperature settings of nitinol specimens fit well into the design goals. Furthermore, we conducted a pilot study to validate the mechanical and physiological performance of nerve ablation without damaging the renal artery. Tensile tests were performed to observe temperature-dependent thermomechanical properties and the original shape of nitinol specimens was set considering our design goal. We performed strain gage experiments to measure bending strain. We developed surgical instrument and operated laparoscopic renal denervation in a swine model. Subsequent impedance spectroscopy experiments were conducted to measure changes in impedance magnitudes during the operation and histological analyses were performed to visualize thermogenic damage to arteries and nerves. Tensile testing showed that the shape memory effect begins above 37 °C. Measured strains on nitinol surfaces were 2.10% ± 0.769%, below the strain limit of 8%. Impedance spectroscopy experiments showed decreases in magnitude in all six trials. After operation of laparoscopic renal denervation following the protocol, renal arteries and nerves were harvested and thermogenic damage was observed in nerves but not arteries. We developed a novel nitinol-actuated surgical instrument with which to perform laparoscopic renal denervation. The feasibility of our device was verified using thermomechanical analyses of nitinol, and assessments of mechanical and physiological performance. Our device could be used in other laparoscopic procedures that require large degrees of freedom while restricting to trocar size.
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http://dx.doi.org/10.1080/02656736.2020.1767806DOI Listing
November 2020

Information Technology-Based Management of Clinically Healthy COVID-19 Patients: Lessons From a Living and Treatment Support Center Operated by Seoul National University Hospital.

J Med Internet Res 2020 06 12;22(6):e19938. Epub 2020 Jun 12.

Department of Family Medicine, Seoul National University Hospital, Seoul, Republic of Korea.

Background: South Korea took preemptive action against coronavirus disease (COVID-19) by implementing extensive testing, thorough epidemiological investigation, strict social distancing, and rapid treatment of patients according to disease severity. The Korean government entrusted large-scale hospitals with the operation of living and treatment support centers (LTSCs) for the management for clinically healthy COVID-19 patients.

Objective: The aim of this paper is to introduce our experience implementing information and communications technology (ICT)-based remote patient management systems at a COVID-19 LTSC.

Methods: We adopted new electronic health record templates, hospital information system (HIS) dashboards, cloud-based medical image sharing, a mobile app, and smart vital sign monitoring devices.

Results: Enhancements were made to the HIS to assist in the workflow and care of patients in the LTSC. A dashboard was created for the medical staff to view the vital signs and symptoms of all patients. Patients used a mobile app to consult with their physician or nurse, answer questionnaires, and input self-measured vital signs; the results were uploaded to the hospital information system in real time. Cloud-based image sharing enabled interoperability between medical institutions. Korea's strategy of aggressive mitigation has "flattened the curve" of the rate of infection. A multidisciplinary approach was integral to develop systems supporting patient care and management at the living and treatment support center as quickly as possible.

Conclusions: Faced with a novel infectious disease, we describe the implementation and experience of applying an ICT-based patient management system in the LTSC affiliated with Seoul National University Hospital. ICT-based tools and applications are increasingly important in health care, and we hope that our experience will provide insight into future technology-based infectious disease responses.
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http://dx.doi.org/10.2196/19938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294904PMC
June 2020

Clinical Desire for an Artificial Intelligence-Based Surgical Assistant System: Electronic Survey-Based Study.

JMIR Med Inform 2020 May 15;8(5):e17647. Epub 2020 May 15.

Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background: Techniques utilizing artificial intelligence (AI) are rapidly growing in medical research and development, especially in the operating room. However, the application of AI in the operating room has been limited to small tasks or software, such as clinical decision systems. It still largely depends on human resources and technology involving the surgeons' hands. Therefore, we conceptualized AI-based solo surgery (AISS) defined as laparoscopic surgery conducted by only one surgeon with support from an AI-based surgical assistant system, and we performed an electronic survey on the clinical desire for such a system.

Objective: This study aimed to evaluate the experiences of surgeons who have performed laparoscopic surgery, the limitations of conventional laparoscopic surgical systems, and the desire for an AI-based surgical assistant system for AISS.

Methods: We performed an online survey for gynecologists, urologists, and general surgeons from June to August 2017. The questionnaire consisted of six items about experience, two about limitations, and five about the clinical desire for an AI-based surgical assistant system for AISS.

Results: A total of 508 surgeons who have performed laparoscopic surgery responded to the survey. Most of the surgeons needed two or more assistants during laparoscopic surgery, and the rate was higher among gynecologists (251/278, 90.3%) than among general surgeons (123/173, 71.1%) and urologists (35/57, 61.4%). The majority of responders answered that the skillfulness of surgical assistants was "very important" or "important." The most uncomfortable aspect of laparoscopic surgery was unskilled movement of the camera (431/508, 84.8%) and instruments (303/508, 59.6%). About 40% (199/508, 39.1%) of responders answered that the AI-based surgical assistant system could substitute 41%-60% of the current workforce, and 83.3% (423/508) showed willingness to buy the system. Furthermore, the most reasonable price was US $30,000-50,000.

Conclusions: Surgeons who perform laparoscopic surgery may feel discomfort with the conventional laparoscopic surgical system in terms of assistant skillfulness, and they may think that the skillfulness of surgical assistants is essential. They desire to alleviate present inconveniences with the conventional laparoscopic surgical system and to perform a safe and comfortable operation by using an AI-based surgical assistant system for AISS.
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http://dx.doi.org/10.2196/17647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260656PMC
May 2020

Comprehensive analysis of mutations of renal cell carcinoma in an autosomal dominant polycystic kidney disease patient.

Medicine (Baltimore) 2020 May;99(19):e20071

Internal Medicine, Hallym University Medical Center, Chuncheon Sacred Heart Hospital, Chuncheon-si, Gangwon-do, Republic of Korea.

Renal cell carcinoma (RCC) is known to be more prevalent in autosomal dominant polycystic kidney disease (ADPKD) patients than in the general population. However, little is known about genetic alterations or changes in signaling pathways in RCC in patients with ADPKD.In the current report, whole-exome and transcriptome sequencing was performed for paired samples of tumor tissue, cyst tissue, and peripheral blood (triple set) from a patient diagnosed with ADPKD and RCC.A 68-year-old man with ADPKD underwent left partial nephrectomy and was diagnosed with RCC. DNA and RNA were extracted from the triple set of the patient. A nonsense mutation in PKD2 (p.Arg742X), which is well known as a pathogenic variant in ADPKD, was identified in the paired triple set. In the tumor sample, a somatic missense mutation of VHL (p.S65L) was found, which is known as a pathogenic mutation in Von Hippel-Lindau syndrome and RCC. Furthermore, loss of chromosome 3p, where VHL is located, was detected. Upregulated VEGFA was found in the analysis of RCC mRNA, which might be caused by the loss of VHL and accelerate angiogenesis in RCC.Proliferation was also expected to be activated by the MAPK signaling pathway, including NRAS and MAPK1 expression.
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http://dx.doi.org/10.1097/MD.0000000000020071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440223PMC
May 2020

Long-term oncologic outcomes after radical prostatectomy in clinically localized prostate cancer: 10-year follow-up in Korea.

Investig Clin Urol 2020 05 21;61(3):269-276. Epub 2020 Apr 21.

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

Purpose: The clinical behavior of prostate cancer differs by race and ethnicity; however, data on the Korean population are scarce. We assessed the long-term oncologic outcomes of clinically localized prostate cancer after radical prostatectomy in Korean men.

Materials And Methods: We analyzed 786 clinically localized prostate cancer patients who underwent radical prostatectomy, from June 1993 to June 2008. Kaplan-Meier survival curve analysis and log-rank test were used to assess the oncologic outcomes.

Results: The mean age of the patients was 64.9±6.6 years. Pelvic lymph node dissection was performed in 373 patients. Pathologic T and N stage cancer with local advancement and invasion were detected by radical prostatectomy in 307 and 22 patients, respectively. In total, 38 patients who underwent adjuvant therapy were excluded from the analysis of progression after biochemical recurrence (BCR), which occurred in 261 men. In total, 219 patients underwent salvage treatment. Local recurrence and distant metastasis occurred in 109 and 42 patients, respectively; 36 patients experienced metastasis with local recurrence. Castration-resistant prostate cancer developed in 22 patients, and overall and disease-specific mortality was noted in 148 and 23 patients, respectively. The median duration from operation to BCR, BCR to metastasis, and metastasis to disease-specific death was 25, 40, and 22 months, respectively.

Conclusions: We demonstrated the long-term prognosis of localized prostate cancer after radical prostatectomy among Koreans. Our results differ from those reported in the Western literature, with a lower prevalence of distant metastasis and shorter time to metastasis after BCR.
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http://dx.doi.org/10.4111/icu.2020.61.3.269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189112PMC
May 2020

Development of the clinical calculator for mortality of patients with metastatic clear cell type renal cell carcinoma: An analysis of patients from Korean Renal Cancer Study Group database.

Investig Clin Urol 2020 05 10;61(3):260-268. Epub 2020 Mar 10.

Anesthesia Consultants of Indianapolis, Indianapolis, IN, USA.

Purpose: To develop the clinical calculator for mortality of patients with metastatic renal cell carcinoma (mRCC) using Korean Renal Cancer Study Group (KRoCS) database.

Materials And Methods: Data from 1,115 patients with mRCC treated in 4 hospitals joining KRoCS between 1993 and 2016 were pooled. Five-year survival rates were calculated using Kaplan-Meier curve. A clinical calculator for 5-year mortality was developed using multivariable logistic regression analysis and validated externally using dataset including 916 patients from 4 other hospitals.

Results: Overall survival rates and cancer specific survival rate at 5 years were 28.5% and 29.4%, respectively. Among baseline factors, increased neutrophil-lymphocyte ratio (≥4), synchronous metastasis, low albumin (<3.0 g/dL), and low hemoglobin (
Conclusions: A clinical calculator has been developed to quantify the risk of death for individual patients after treatment of mRCC. This tool may be useful for patients or their guardians who want to know their prognosis and to identify patients requiring aggressive therapy and additional supportive measures during and after treatment.
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http://dx.doi.org/10.4111/icu.2020.61.3.260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189103PMC
May 2020