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.

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.

Role of lymphatic invasion in predicting biochemical recurrence after radical prostatectomy.

Objective: Lymphatic invasion in prostate cancer is associated with poor prognosis. However, there is no consensus regarding the clinical and prognostic value of lymphatic invasion. This study aimed to investigate the prognostic value of lymphatic invasion in biochemical recurrence (BCR) and compare the recurrence rates between patients with lymphatic invasion and lymph node metastasis. Methods: We retrospectively analyzed 2,207 patients who underwent radical prostatectomy (RP) without pelvic lymph node dissection (PLND) and 742 patients who underwent RP with PLND for clinically localized or locally advanced prostate cancer, between 1993 and 2020, at Seoul National University Hospital. Kaplan-Meier analysis was performed to estimate BCR-free survival (BCRFS) using the log-rank test. The Cox proportional hazards model was used to identify the significant factors for BCR. Propensity score matching was performed with a 1:2 ratio to match age, initial PSA level, pathological T stage, and Gleason score to exclude confounding effects. Results: Of the 2,207 patients who underwent RP without PLND, lymphatic invasion (L1Nx) was observed in 79 (3.5%) individuals. Among the 742 patients who underwent RP with PLND, lymph node metastases were found in 105 patients (14.2%). In patients with lymph node metastasis, lymphatic invasion was observed in 50 patients (47.6%), whereas lymphatic invasion was observed in 53 patients (8.3%) among those without lymph node metastasis. In patients who underwent RP without PLND, Kaplan-Meier analysis showed significantly poorer BCR-free survival in the L1Nx group than in the L0Nx group (p < 0.001). In patients who underwent RP with PLND, the L1N0, L0N1, and L1N1 groups showed significantly worse prognoses than the L0N0 group (p < 0.001). However, there was no significant difference in BCRFS between the L1N0 and lymph node metastasis groups, including the L0N1 and L1N1 groups. After propensity score matching at a 1:2 ratio, the L1Nx group showed significantly poorer outcomes in terms of BCRFS than the L0Nx group (p = 0.05). In addition, the L1N0 group showed a significantly worse prognosis than the L0N0 group after propensity score matching. Conclusion: Lymphatic invasion in radical prostatectomy specimens is an independent prognostic factor, which can complement lymph node status for predicting biochemical recurrence. Considering lymphatic invasion as an adverse pathological finding, similar to lymph node metastasis, adjuvant therapy could be considered in patients with lymphatic invasion.

A prospective, multicenter study on the clinical effectiveness of abiraterone in metastatic castration-resistant prostate cancer in Korea: Pre- vs. post-chemotherapy.

PURPOSE: The proper treatment sequence for administering abiraterone acetate plus prednisolone (AAP) and chemotherapeutic agents has not yet been elucidated for metastatic castration-resistant prostate cancer (mCRPC). Hence, this study evaluated the effectiveness and safety of AAP in pre- and post-chemotherapy settings using real-world data. MATERIALS AND METHODS: This prospective, multicenter, open-label, observational study included 506 patients with mCRPC. Patients were classified according to the timing of chemotherapy into pre- and post-chemotherapy groups. The effectiveness and safety of AAP were compared between the groups; the prostate-specific antigen (PSA) response, PSA progression-free survival, and radiologic progression-free survival were assessed; and adverse drug reactions were recorded. RESULTS: Among the included patients, 319 and 187 belonged to the pre- and post-chemotherapy groups, respectively. Risk classification was similar between the two groups. The PSA response was 61.8% in the pre-chemotherapy group and 39.0% in the post-chemotherapy group (p<0.001). The median time to PSA progression (5.00 vs. 2.93 mo, p=0.001) and radiologic progression-free survival (11.84 vs. 9.17 mo, p=0.002) were significantly longer in the pre-chemotherapy group. Chemotherapy status was associated with PSA (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.09-1.77) and radiologic progression (HR 1.66, 95% CI 1.18-2.33) during AAP treatment. Adverse drug reactions were reported at similar frequencies in both groups. CONCLUSIONS: In this postmarketing surveillance, AAP benefited patients with mCRPC, especially in settings before chemotherapy was administered, resulting in a high PSA response and longer PSA and radiologic progression-free survival with tolerable adverse drug reactions.

Pyuria as an independent predictor of intravesical recurrence after radical nephroureterectomy in patients with upper tract urothelial carcinoma.

PURPOSE: About one-third of patients who undergo radical nephroureterectomy (RNUx) for upper tract urothelial carcinoma (UTUC) experience intravesical recurrence (IVR). This study investigated whether pyuria is a feasible predictor of IVR after RNUx in patients with UTUC. MATERIALS AND METHODS: Seven hundred forty-three patients with UTUC who underwent RNUx at a single institute were analyzed in this study. The participants were divided into two groups: those without pyuria (non-pyuria) and those with pyuria. Kaplan-Meier survival analysis was performed, and p-values were assessed using the log-rank test. Cox regression analyses were performed to identify the independent predictors of survival. RESULTS: The pyuria group had a shorter IVR-free survival period (p=0.009). The five-year IVR-free survival rate was 60.0% in the non-pyuria group vs. 49.7% in the pyuria group according to the Kaplan-Meier survival analysis. After the multivariate Cox regression analysis, pyuria (hazard ratio [HR]=1.368; p=0.041), a concurrent bladder tumor (HR=1.757; p=0.005), preoperative ureteroscopy (HR=1.476; p=0.013), laparoscopic surgery (HR=0.682; p=0.048), tumor multiplicity (HR=1.855; p=0.007), and a larger tumor (HR=1.041; p=0.050) were predictors of risk for IVR. There was no association between pyuria and recurrence-free survival (p=0.057) or cancer-specific survival (p=0.519) in the Kaplan-Meier survival analysis. CONCLUSIONS: This study concluded that pyuria was an independent predictor of IVR in patients with UTUC after RNUx.

Practical Utility of Liquid Biopsies for Evaluating Genomic Alterations in Castration-Resistant Prostate Cancer.

Traditional tissue-based assessments of genomic alterations in castration-resistant prostate cancer (CRPC) can be challenging. To evaluate the real-world clinical utility of liquid biopsies for the evaluation of genomic alterations in CRPC, we preemptively collected available plasma samples and archival tissue samples from patients that were being treated for clinically confirmed CRPC. The cell-free DNA (cfDNA) and tumor tissue DNA were analyzed using the AlphaLiquid®100-HRR panel. Plasma samples from a total of 87 patients were included in this study. Somatic mutations from cfDNA were detected in 78 (89.7%) patients, regardless of the presence of overt metastasis or concomitant treatment given at the time of plasma sample collection. Twenty-three patients were found to have known deleterious somatic or germline mutations in HRR genes from their cfDNA. Archival tissue samples from 33 (37.9%) patients were available for comparative analysis. Tissue sequencing was able to yield an NGS result in only 51.5% of the tissue samples. The general sensitivity of cfDNA for detecting somatic mutations in tissues was 71.8%, but important somatic/germline mutations in HRR genes were found to have a higher concordance (100%). Liquid biopsies can be a reasonable substitute for tissue biopsies in CRPC patients when evaluating genomic alterations.

Accuracy of actual stage prediction using Vesical Imaging Reporting and Data System (VI-RADS) before radical cystectomy for urothelial carcinoma in SUPER-UC-Cx.

Background: Previous studies using the Vesical Imaging Reporting and Data System (VI-RADS) to predict muscle-invasive bladder cancer (MIBC) had some limitations. Most studies were performed with transurethral resection of bladder tumor (TUR-BT) specimens with few samples. This study was conducted to address these shortcomings and confirm the accuracy of VI-RADS for bladder cancer. Methods: This study used data from the Seoul National University Prospectively Enrolled Registry for Urothelial Cancer-Radical Cystectomy (SUPER-UC-Cx). Patients who underwent multiparametric magnetic resonance imaging (mp-MRI) before radical cystectomy (RC) were included in this study between March 2020 and March 2022. All images were reported by radiologists and reviewed by two urologists. The patient characteristics and clinical information were blinded during the review. The performance of qualitative and quantitative variables in predicting muscle layer invasion or perivesical fat infiltration was verified by receiver operating characteristic (ROC) curve analysis. Results: Of 208 patients, 182 (87.5%) underwent mp-MRI before RC. Twenty-three patients with non-urothelial carcinoma, inappropriate MRI scans, and bladder filling were excluded. Cut-off for muscle invasion, VI-RADS score of 4 had the highest area under the curve (AUC) (sensitivity 0.84; specificity 0.93; accuracy 0.90; positive predictive value (PPV) 0.84; negative predictive value (NPV) 0.93, and AUC 0.88). Cut-off for perivesical fat invasion and VI-RADS score of 5 had the highest AUC (sensitivity, 0.78; specificity, 0.99; accuracy, 0.95; PPV, 0.96; NPV, 0.95; and AUC, 0.89). Conclusions: VI-RADS is a good predictor of bladder cancer staging before RC and is especially helpful in predicting muscle invasion and perivesical fat infiltration.

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).

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.

Increased urinary B2-microglobulin is associated with poor prognosis of upper tract urothelial carcinoma.

Background: Kidney tubular damage markers are biomarkers of acute or chronic kidney injury. Hypothetically, upper tract urothelial cancer (UTUC), which induces obstructive uropathy or direct invasion of the renal parenchyma, may also induce increased excretion of urinary tubular damage proteins. Therefore, this study aimed to investigate the use of tubular damage biomarker as prognostic markers for UTUC. Methods: The records of 417 surgically resected patients with UTUC were obtained from the Seoul National University Prospectively Enrolled Registry for urothelial cancer-upper tract urothelial cancer (SUPER-UC-UTUC) between January 2016 and December 2020. Patients with non-urothelial cancer or without urinary tubular injury marker measurement were excluded, and finally, 296 patients were finally included. B2-microglobulin (B2-MG) was an injury marker, and a value higher than 0.3 was considered abnormally elevated, according to previous studies. Results: The mean age was 70.9 years, and the male sex was predominant (n = 211, 71.3%). The incidences of renal pelvis and ureter cancer were similar (50.7% vs. 49.3%). Most patients had high-grade diseases (n = 254, 88.8%). The high urine B2-MG group was older, had decreased renal function, and had a higher pathologic T stage than did the low group. Multivariate Cox regression analysis of disease-free survival (DFS), open surgical method (Hazard ratio (HR) 1.52, p = 0.027), large tumor size (HR 1.06, p = 0.017), tumor multifocality (HR 1.90, p = 0.038), lymphovascular invasion (HR 2.19, p < 0.001), and high urine B2-MG (HR 1.57, p = 0.021) were significantly associated with shortened metastasis-free survival (MFS). Kaplan-Meier curve analysis revealed short DFS (median survival 15.5 months vs. unattained, log-rank p = 0.001) and MFS (unattained median survival in both groups, log-rank p = 0.003) for the high urine B2-MG group compared to the low urine B2-MG group. Conclusion: Patients with UTUC presenting with increased pre-operative urine B2-MG levels were associated with disease recurrence and metastasis. This biomarker may aid in performing pre-operative risk stratification and in assessing the individual prognosis of patients with UTUC.

Acidic urine is associated with poor prognosis in patients with bladder cancer undergoing radical cystectomy.

Purpose: To assess the prognostic value of acidic urine (low urine pH) in patients with bladder cancer undergoing radical cystectomy. Materials and methods: We reviewed patients enrolled in the Seoul National University Prospectively Enrolled Registry for Urothelial Cancer-Cystectomy (SUPER-UC-Cx) who underwent radical cystectomy for bladder cancer between March 2016 and December 2020 at the Seoul National University Hospital. During this period, 368 patients were registered in our database. To eliminate confounding factors, we excluded patients diagnosed with non-urothelial cancer and end-stage renal disease. Results: A total of 351 patients with a mean age of 69.8 ± 10.5 years and median follow-up of 16.0 months were eligible for the analysis. The mean preoperative urine pH was 6.0. The patients were divided into low (pH ≤ 5.5) and high (pH≥6.0) urine pH groups for comparison. All clinicopathological features, including the tumor size, grade, and stage were comparable between the low and high urine pH groups. A Cox regression analysis was performed to assess the independent effect of acidic urine on patient survival. A multivariate analysis showed that high T stage (T3-4) (hazard ratio (HR) 5.18, P<0.001), decreased renal function (estimated glomerular filtration rate <60 mL/min/1.73 m2) (HR 2.29, P=0.003), and low urine pH (≤5.5) (HR 1.69, P=0.05) were associated with shortened recurrence-free survival (RFS). Regarding the overall survival (OS), high T stage (T3-4) (HR 7.15, P<0.001) and low urine pH (≤5.5) (HR 2.66, P=0.029) were significantly associated with shortened survival. A Kaplan-Meier analysis demonstrated that the acidic urine group showed shorter RFS (P=0.04) and OS (P=0.028) than the other groups. Conclusions: Acidic urine was independently associated with reduced RFS and OS in patients with bladder cancer undergoing radical cystectomy. Acidic urine contributing to an acidic tumor environment may promote aggressive behavior in bladder cancer.

High Carbohydrate Antigen 19-9 Levels Indicate Poor Prognosis of Upper Tract Urothelial Carcinoma.

Upper tract urothelial carcinoma (UTUC) occurs in urothelial cells from the kidney and the ureters. Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker for pancreatic and gastrointestinal cancers, and its high levels are associated with poor prognosis in bladder cancer. In this study, prospective patients enrolled in the registry of Seoul National University were retrospectively examined to determine the clinical significance of CA 19-9 in UTUC. In 227 patients, high serum CA 19-9 levels reflected a high tumor burden represented by high T and N stages, leading to adverse prognosis in metastasis-free or overall survival. Subsequently, propensity score matching analysis showed that the CA 19-9 level is an independent prognostic factor of UTUC.

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.

Gatekeeping role of Nf2/Merlin in vascular tip EC induction through suppression of VEGFR2 internalization.

In sprouting angiogenesis, the precise mechanisms underlying how intracellular vascular endothelial growth factor receptor 2 (VEGFR2) signaling is higher in one endothelial cell (EC) compared with its neighbor and acquires the tip EC phenotype under a similar external cue are elusive. Here, we show that Merlin, encoded by the neurofibromatosis type 2 (NF2) gene, suppresses VEGFR2 internalization depending on VE-cadherin density and inhibits tip EC induction. Accordingly, endothelial Nf2 depletion promotes tip EC induction with excessive filopodia by enhancing VEGFR2 internalization in both the growing and matured vessels. Mechanistically, Merlin binds to the VEGFR2-VE-cadherin complex at cell-cell junctions and reduces VEGFR2 internalization-induced downstream signaling during tip EC induction. As a consequence, nonfunctional excessive sprouting occurs during tumor angiogenesis in EC-specific Nf2-deleted mice, leading to delayed tumor growth. Together, Nf2/Merlin is a crucial molecular gatekeeper for tip EC induction, capillary integrity, and proper tumor angiogenesis by suppressing VEGFR2 internalization.

Urinary Markers for Bladder Cancer Diagnosis and Monitoring.

Hematuria is a typical symptom of bladder cancer which enables early detection of bladder cancer. However, reliable diagnostic tools for bladder cancer using urine samples or other non-invasive methods are lacking. Tremendous attempts have been tried and revealed fancy works to convey definitive diagnostic power using urine samples. In this paper, we reviewed urinary markers for bladder cancer and compared their efficacies.

Safety and feasibility of synchronous unilateral nephrectomy and contralateral heminephrectomy for extremely severe autosomal dominant polycystic kidney disease: Techniques and outcome.

PURPOSE: To demonstrate the safety and feasibility of synchronous unilateral nephrectomy and contralateral heminephrectomy in extremely severe autosomal dominant polycystic kidney disease (ADPKD), which corresponds to the Mayo imaging classification classes 1D and 1E. MATERIALS AND METHODS: We retrospectively reviewed patients who underwent unilateral nephrectomy and contralateral heminephrectomy at the Seoul National University Hospital (Seoul, Korea) between May 1, 2016 and August 1, 2021. The preoperative kidney volume was calculated using the ellipsoid equation (length×width×thickness×π/6). The Mayo imaging classification was determined by height-adjusted total kidney volume and age. Using a midline vertical incision, heminephrectomy was performed first by horizontal transection, followed by contralateral nephrectomy. Hilar vessel clamping or resection-bed suturing was not required. RESULTS: In all, nine patients with ADPKD of the highest severity (Mayo class 1D/1E) underwent unilateral heminephrectomy and contralateral nephrectomy for the most common cause of severe abdominal discomfort and malnutrition. All nine patients had end-stage renal disease with hypertension and anemia. The median preoperative total kidney volume was 10,905.8 mL (interquartile range [IQR], 8,170.4-16,227.6 mL). The median operation time was 140 minutes (IQR, 125-185 min) and the median estimated blood loss was 250 mL (IQR, 200-425 mL). Eight of the nine patients were discharged without ICU care or any complications. Delayed pseudoaneurysm occurred in one case and was successfully managed by embolization. All patients were symptom-free for a median follow-up period of 2 years. CONCLUSIONS: Synchronous unilateral nephrectomy and contralateral heminephrectomy are safe and feasible treatment options for severe bilateral ADPKD.

Evaluating the efficacy of secondary transurethral resection of the bladder for high-grade Ta tumors.

PURPOSE: The need for secondary transurethral resection of the bladder (re-TURB) in patients with high-grade Ta tumors has not been assessed. This study aimed to compare the outcomes of patients with high-grade Ta tumors who did and did not undergo re-TURB. MATERIALS AND METHODS: This study used data from the Seoul National University Prospectively Enrolled Registry for Urothelial Cancer-Transurethral Bladder Tumor Resection (SUPER-UC-TURB). Patients with high-grade Ta tumors who underwent TURB between March 2016 and December 2019 were included. Following the initial TURB, if the pathology results showed a tumor grade higher than high-grade Ta, re-TURB was performed according to the surgeon's recommendation. The recurrence-free survival rate was assessed by Kaplan-Meier analysis and Cox regression analysis between patients who did and did not undergo re-TURB. RESULTS: In total, 187 patients with high-grade Ta who underwent initial TURB were included, of whom 115 underwent re-TURB and 72 did not. Patients in the re-TURB group had a significantly higher 2-year recurrence-free survival rate than did those in the no re-TURB group (81.3% vs. 60.1%; p=0.005). Whether patients underwent re-TURB was a significant predictor of the risk of bladder cancer recurrence in both the univariate (HR, 0.52; 95% CI, 0.27-0.98; p=0.044) and multivariate (HR, 0.41; 95% CI, 0.19-0.97; p=0.041) analysis. CONCLUSIONS: The risk for bladder cancer recurrence was increased, and the 2-year recurrence-free survival was significantly decreased, in patients with high-grade Ta tumors who did not undergo re-TURB. Thus, re-TURB is beneficial in patients with high-grade Ta bladder cancer.

Immunotherapy for prostate cancer: Requirements for a successful regime transfer.

Despite the revolutionary progress in cancer treatment using immune checkpoint inhibitors (ICIs), remarkable responses in prostate cancer treatment have not yet been achieved. The disappointing previous results of ICIs have required further studies towards combined treatment targeting other pathways and restricted the eligibility criteria for patients with high mutation burdens, especially those with mismatch repair deficiency. Cancer immunotherapies activate adaptive immune systems, rather than directly attack tumor cells with their own cytotoxicity. Therefore, refractoriness to ICIs can not only be derived from the intractable nature of tumor cells per se , but also from their hostile milieu. Here, we reviewed the prostate cancer immunotherapies exploring clinical trials to date, along with the molecular characteristics of prostate cancer and its microenvironment.

Conformable microneedle pH sensors via the integration of two different siloxane polymers for mapping peripheral artery disease.

Flexible microneedles are important tools that allow access to the inside of biological tissue from the outside without surgery. However, it had been hard to realize microneedle sensor arrays on flexible substrates because of the difficulty of attaining a needle with a high Young's modulus for a selected area on a thin or soft substrate. In this work, we developed a microneedle sensor on a hybrid substrate based on high Young's modulus epoxy siloxane for the microneedles and low Young's modulus polydimethylsiloxane for the conformable substrate. Polyaniline was deposited on the microneedle for pH sensing. The mechanical durability of the device was assessed by insertion into pig skin 1000 times. Last, the flexible microneedle pH sensors showed their utility for monitoring pH distribution in rats in a peripheral artery diseases model.