Polygenic risk score model for renal cell carcinoma in the Korean population and relationship with lifestyle-associated factors.

BACKGROUND: The polygenic risk score (PRS) is used to predict the risk of developing common complex diseases or cancers using genetic markers. Although PRS is used in clinical practice to predict breast cancer risk, it is more accurate for Europeans than for non-Europeans because of the sample size of training genome-wide association studies (GWAS). To address this disparity, we constructed a PRS model for predicting the risk of renal cell carcinoma (RCC) in the Korean population. RESULTS: Using GWAS analysis, we identified 43 Korean-specific variants and calculated the PRS. Subsequent to plotting receiver operating characteristic (ROC) curves, we selected the 31 best-performing variants to construct an optimal PRS model. The resultant PRS model with 31 variants demonstrated a prediction rate of 77.4%. The pathway analysis indicated that the identified non-coding variants are involved in regulating the expression of genes related to cancer initiation and progression. Notably, favorable lifestyle habits, such as avoiding tobacco and alcohol, mitigated the risk of RCC across PRS strata expressing genetic risk. CONCLUSION: A Korean-specific PRS model was established to predict the risk of RCC in the underrepresented Korean population. Our findings suggest that lifestyle-associated factors influencing RCC risk are associated with acquired risk factors indirectly through epigenetic modification, even among individuals in the higher PRS category.

Rate of benign histology after resection of suspected renal cell carcinoma: multicenter comparison between Korea and the United States.

BACKGROUND: In the United States, the rate of benign histology among resected renal tumors suspected to be malignant is increasing. We evaluated the rates in the Republic of Korea and assessed the racial effect using recent multi-institutional Korean-United States data. METHODS: We conducted a multi-institutional retrospective study of 11,529 patients (8,812 from The Republic of Korea and 2,717 from the United States) and compared the rates of benign histology between the two countries. To evaluate the racial effect, we divided the patients into Korean, Asian in the US, and Non-Asian in the US. RESULTS: The rates of benign histology and small renal masses in Korean patients were significantly lower than that in United States patients (6.3% vs. 14.3%, p < 0.001) and (≤ 4 cm, 7.6% vs. 19.5%, p < 0.001), respectively. Women, incidentaloma, partial nephrectomy, minimally invasive surgery, and recent surgery were associated with a higher rate of benign histology than others. CONCLUSIONS: In Korea, the rate of benign histology among resected renal tumors was significantly lower than that in the United States. This disparity could be caused by environmental or cultural differences rather than racial differences. Our findings suggest that re-evaluating current context-specific standards of care is necessary to avoid overtreatment.

Tubular damage marker as a predictive factor for pathologically upstaged renal cell carcinoma.

PURPOSE: To investigate if increased tubular damage biomarker can predict pathologically upstaged renal cell carcinoma (RCC), which may possess sub-radiologic invasive behavior, leading to surrounding tubular damage. MATERIALS AND METHODS: We examined 1563 patients with surgically resected RCC between March 2016 and June 2021 from the prospective database SUPER-RCC-Nx. Exclusion criteria were cancer not originating from the kidneys, benign renal tumor, and end-stage renal disease. RESULTS: Of 1297 patients, 131 had a clinically high T stage (T3-4), whereas 1166 had a low one. Patients with a clinically low T stage were subgrouped into identical-stage (n = 1041) and upstaged (n = 125) groups, who were confirmed as a pathologically high T stage. The upstaged group had older age (p = 0.003), larger tumor size (5.72 ± 3.24 vs. 3.12 ± 2.08, p < 0.001), higher Fuhrman grade (grades 3-4) (57.3% vs. 47.1%, p = 0.032), and higher urine N-acetyl-beta-D-glucosaminidase/creatinine (NAG/Cr) (5.13 ± 4.78 vs. 4.05 ± 2.84, p = 0.026). Tumor size (> 4 cm; odds ratio = 10.2, p < 0.001) and urine NAG/Cr (odds ratio = 1.16, p = 0.003) were independently associated with pathological upstaging in patients with normal renal function, while age and tumor size were significant risk factors in those with decreased renal function. The receiver operating characteristic curve analysis showed that the model using tumor size and urine NAG/Cr strongly predicted pathological upstaging (area under the curve, 0.84). CONCLUSION: Urine NAG/Cr may be a useful biomarker predicting pathologically upstaged RCC. Clinicians should be prudent in making management decisions when a large RCC is accompanied by an increased urine NAG/Cr.

Clinical features and Surgical Outcome of Clear Cell Papillary Renal Cell Tumor: result from a prospective cohort.

BACKGROUND: Clear cell papillary renal cell tumor (CCPRCT) was first reported in 2006 a patient with end stage renal disease. After that it was discovered in the kidney without end stage renal disease in the 2010s and started to be mentioned in pathology and urology. The incidence of CCPRCT is low and most of it is discovered incidentally, so there is a lack of reports on clinical characteristics and surgical outcome. METHODS: This study used clinical data from the Seoul National University Prospectively Enrolled Registry for Renal Cell Carcinoma-Nephrectomy (SUPER-RCC-Nx). Between August 2016 and July 2022, patients who underwent radical or partial nephrectomy with clear cell papillary RCC with pathological finding were included in this study. All patients' pathologic reports were reviewed by 1 pathologist. Clinical characteristics and surgical outcomes were presented through descriptive statistics, and Kaplan-Meier curve used for survival analysis. RESULTS: Of the 2057 patients, CCPRCT was reported in 36 patients (1.8%). The median follow up period was 26.8 months. The median age was 67 years, and there were 10 females and 26 males. The median tumor size was 1.2 cm. Twenty-nine patients underwent partial nephrectomy. Seven patients with end-stage renal disease underwent radical nephrectomy. The median operative time for patients who underwent partial nephrectomy was 97.5 min and the estimated blood loss was 100 cc. The median hospital days was 4 and 30-day complications were 2 cases with clavien-dindo classification III or higher. During the follow-up period, there was no recurrence and cancer specific mortality. CONCLUSIONS: The size of CCPRCT was small and there was no advanced stage at that time of diagnosis. There was no recurrence or cancer specific mortality during the follow-up period. A multi-center study with a large scale is needed in the future. TRIAL REGISTRATION: Seoul National University Hospital (SNUH) Institutional Review Board (IRB) (approval number: 2210-126-1371).

Serum biochemical reference interval determination in wild Siberian weasel (Mustela sibirica).

Determining reference intervals (RI) is a valuable asset for assessing the health of wildlife species. This is the first study to establish serum biochemical RIs in Siberian weasels. Forty-two healthy free-ranging Siberian weasels were captured live and brought to Seoul Wildlife Center between June 2021 and August 2022. Blood samples from 42 healthy Siberian weasels of both sexes were used to calculate RIs. An automated analyser was used to perform serum biochemistry profiles. The American Society for Veterinary Clinical Pathology recommendations were used to calculate a nonparametric RI with 90% confidence intervals. The RIs of albumin, total protein, globulin, calcium, glucose, blood urea nitrogen, phosphorus, amylase, cholesterol, alanine aminotransferase, total bilirubin, alkaline phosphatase, creatinine, and creatine kinase were determined. The RIs established in this study will serve as a good starting point for analysing serum biochemical data in Siberian weasels.

VERTEBRAL HEART SCALE SYSTEM IN CLINICALLY HEALTHY SIBERIAN WEASEL (MUSTELA SIBIRICA).

In several species, the vertebral heart scale (VHS) measurement is frequently used to provide a more objective evaluation of cardiomegaly. However, normal-sized parameters for radiographic measures of the cardiac silhouette in Siberian weasels (Mustela sibirica) have not been determined. Right lateral (n = 24) and ventrodorsal (n = 20) thoracic radiographs from free-ranging Siberian weasels with clinically normal cardiac and pulmonary function were acquired and evaluated to determine the specific VHS for the Siberian weasel. The mean (SD) VHS of the right lateral (RL) and the ventrodorsal (VD) views were 6.70 (0.60) and 6.95 (0.69), respectively. VD view radiographs had a considerably higher VHS than RL view radiographs, and RL view measures were less variable than VD view values. The VHS of Siberian weasels was unaffected by age, body weight, or sex. The results determined in this study can be used in clinical diagnostic and radiographic evaluations of Siberian weasels.

Clinical determinants of recurrence in pTa bladder cancer following transurethral resection of bladder tumor.

BACKGROUND: Non-muscle invasive bladder cancer can be controlled by transurethral resection of bladder (TURB), but suffers from frequent recurrences in 60-70% of cases. Although, recurrence interval after TURB influences treatment course and prognosis, its implication and risk factors have not been fully elucidated. We evaluated the risk factors of early (within 1 yr) and late (after 1 yr) recurrence of pTa bladder cancer and clinical significance of recurrence interval on disease progression and overall survival. METHODS: In this study, pTa bladder cancer patients enrolled in prospective patient registry system of Seoul National University, SUPER-UC, were retrospectively examined to determine the clinical risk factors for recurrence and its significance regarding to recurrence interval. A total of 1067 bladder cancer patients who underwent TURB between March 20 and June 2021 were included and classified into three groups of no recurrence, early, or late recurrence to be comparatively analyzed. RESULTS: Early recurrence was associated with poorer cystectomy-free survival and overall survival than late recurrence. Risk factors for early recurrence included a high number of previous TURB, tumor multiplicity, tumor location, tumor shape, incompleteness of TURB, and high tumor grade. Otherwise, late recurrence was associated with low-grade tumors with insufficient TURB depth. CONCLUSION: Patients with risk factors for early recurrence should be closely followed up with special cautions.

Association between decreased ipsilateral renal function and aggressive behavior in renal cell carcinoma.

BACKGROUND: To assess prognostic value of pre-operative ipsilateral split renal function (SRF) on disease-free survival (DFS) and its association with aggressive pathological features in renal cell carcinoma (RCC) patients.  METHODS: We examined patients registered in SNUG-RCC-Nx who underwent partial or radical nephrectomy at Seoul National University Hospital between January 1, 2010 and December 31, 2020. Patients with the following criteria were excluded from the study. 1) non-kidney origin cancer or benign renal tumor, 2) no pre-operative Tc 99 m-DTPA renal scan, 3) single kidney status or previous partial or radical nephrectomy, and 4) bilateral renal mass. Finally, 1,078 patients were included. RESULTS: Among 1,078 patients, 899 (83.4%) showed maintained ipsilateral SRF on DTPA renal scan; 179 patients (16.6%) showed decreased SRF. The decreased SRF group showed significantly large tumor size (maintained vs. decreased SRF; 3.31 ± 2.15 vs. 6.85 ± 3.25, p < 0.001), high Fuhrman grade (grade 3-4) (41.7% vs. 55.6%, p < 0.001), and high T stage (T stage 3-4) (9.0% vs. 20.1%, p < 0.001). Pathological invasive features, including invasion of the renal capsule, perirenal fat, renal sinus fat, vein, and collecting duct system, were associated with low SRF of the ipsilateral kidney. Univariate Cox regression analysis identified higher SSIGN (The stage, size, grade, and necrosis) score and decreased ipsilateral SRF as significant risk factors, while multivariate analysis showed SSIGN (5-7) (hazard ratio [HR] 11.9, p < 0.001) and SSIGN (8-10) (HR 69.2, p < 0.001) were significantly associated with shortened DFS, while decreased ipsilateral SRF (HR 1.75, p = 0.065) showed borderline significance. Kaplan-Meier analysis showed that decreased ipsilateral SRF (< 45%) group had shorter DFS than the other group (median DFS: 90.3 months vs. not reached, p < 0.001). CONCLUSIONS: Among unilateral RCC patients, those with low ipsilateral SRF showed poor prognosis with pathologically invasive features. Our novel approach may facilitate risk stratification in RCC patients, helping formulate a treatment strategy.

Gold(I)-Catalyzed Intramolecular Hydrothiophenylation of N-Thiophen-3-yl Alkynylamides for Accessing Thieno[3,2-b]pyridine-5(4H)-ones: Development of F-Actin Specific Fluorescent Probes.

Herein, we describe an original synthetic method for a series of fluorescent thieno[3,2-b]pyridine-5(4H)-one derivatives prepared via the gold(I)-catalyzed 6-endo-dig intramolecular hydrothiophenylation process involving N-thiophen-3-yl alkynylamides. The brightness was improved; emission could be tuned, and larger Stokes shifts were recorded. We also designed and synthesized the phalloidin-based fluorescent chemical probes KF-P1 and KF-P2 to realize fluorescent F-actin imaging.

Clinical significance of peripheral zone thickness in men with lower urinary tract symptoms/benign prostatic hyperplasia.

OBJECTIVE: To evaluate the clinical impact of prostate peripheral zone thickness (PZT), based on presumed circle area ratio (PCAR) theory, on urinary symptoms in men with lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH) as a novel prostate parameter. PATIENTS AND METHODS: Medical records were obtained from a prospective database of first-visit men with LUTS/BPH. Age, international prostate symptom score (IPSS), overactive bladder symptom score (OABSS), maximum urinary flow rate (Qmax ), and post-void residual urine volume (PVR) were assessed. Total prostate volume (TPV), transition zone volume (TZV), transition zone index (TZI), and PZT were measured by transrectal ultrasonography. Reliability analysis was also performed. RESULTS: In all, 1009 patients were enrolled for the analysis. The mean (sd) PZT was 11.10 (2.50) mm, and patients were classified into three groups PZT thickness groups; PZT <9.5 mm, ≥9.5 to <13 mm, and ≥13 mm. As the PZT became smaller, all urinary symptom scores including IPSS, quality of life (QoL), and OABSS significantly increased. Uroflowmetry variables, such as Qmax and PVR, also showed significant differences. PZT showed a high intra-class correlation coefficient (0.896). Multivariate analysis revealed that the PZT was independently associated with IPSS (P < 0.001), QoL (P = 0.003), OABSS (P = 0.001), and PVR (P = 0.001), but PZT influence on Qmax was only of borderline significance (P = 0.055). CONCLUSION: PZT is a novel, easy-to-measure prostate parameter that is significantly associated with urinary symptoms. Our present findings suggest that clinical usefulness of PZT should be further validated for managing men with LUTS/BPH.