CRISPR/Cas9 targeting of passenger single nucleotide variants in haploinsufficient or essential genes expands cancer therapy prospects.

CRISPR/Cas9 technology has effectively targeted cancer-specific oncogenic hotspot mutations or insertion-deletions. However, their limited prevalence in tumors restricts their application. We propose a novel approach targeting passenger single nucleotide variants (SNVs) in haploinsufficient or essential genes to broaden therapeutic options. By disrupting haploinsufficient or essential genes through the cleavage of DNA in the SNV region using CRISPR/Cas9, we achieved the selective elimination of cancer cells without affecting normal cells. We found that, on average, 44.8% of solid cancer patients are eligible for our approach, a substantial increase compared to the 14.4% of patients with CRISPR/Cas9-applicable oncogenic hotspot mutations. Through in vitro and in vivo experiments, we validated our strategy by targeting a passenger mutation in the essential ribosomal gene RRP9 and haploinsufficient gene SMG6. This demonstrates the potential of our strategy to selectively eliminate cancer cells and expand therapeutic opportunities.

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.

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.

Oncological Outcomes in Men with Metastatic Castration-Resistant Prostate Cancer Treated with Enzalutamide with versus without Confirmatory Bone Scan.

PURPOSE: In men with metastatic castration-resistant prostate cancer (mCRPC), new bone lesions are sometimes not properly categorized through a confirmatory bone scan, and clinical significance of the test itself remains unclear. This study aimed to demonstrate the performance rate of confirmatory bone scans in a real-world setting and their prognostic impact in enzalutamide-treated mCRPC. MATERIALS AND METHODS: Patients who received oral enzalutamide for mCRPC during 2014-2017 at 14 tertiary centers in Korea were included. Patients lacking imaging assessment data or insufficient drug exposure were excluded. The primary outcome was overall survival (OS). Secondary outcomes included performance rate of confirmatory bone scans in a real-world setting. Kaplan-Meier analysis and multivariate Cox regression analysis were performed. RESULTS: Overall, 520 patients with mCRPC were enrolled (240 [26.2%] chemotherapy-naïve and 280 [53.2%] after chemotherapy). Among 352 responders, 92 patients (26.1%) showed new bone lesions in their early bone scan. Confirmatory bone scan was performed in 41 patients (44.6%), and it was associated with prolonged OS in the entire population (median, 30.9 vs. 19.7 months; p < 0.001), as well as in the chemotherapy-naïve (median, 47.2 vs. 20.5 months; p=0.011) and post-chemotherapy sub-groups (median, 25.5 vs. 18.0 months; p=0.006). Multivariate Cox regression showed that confirmatory bone scan performance was an independent prognostic factor for OS (hazard ratio 0.35, 95% confidence interval, 0.18 to 0.69; p=0.002). CONCLUSION: Confirmatory bone scan performance was associated with prolonged OS. Thus, the premature discontinuation of enzalutamide without confirmatory bone scans should be discouraged.

Novel laparoscopic renal denervation immediately reduces atrial fibrillation inducibility: a swine model study.

Catheter-based approaches may have inherent limitations in achieving effective renal denervation (RDN) and treatment of atrial fibrillation (AF). This study aimed to investigate the acute effects of novel laparoscopic RDN on modulating AF inducibility using a swine model. Four and five swine were randomly allocated to the sham and RDN groups, respectively. Each swine underwent measurement of the atrial effective refractory period (AERP) and AF induction tests using burst atrial pacing before and immediately after sham or RDN procedures with and without vagal nerve stimulation (VNS). A laparoscopic RDN procedure circumferentially ablated the renal nerves round the renal arteries using radiofrequency energy. There was no significant difference in the baseline AERP between the two groups (p > 0.05). Under VNS, AERP was significantly increased by 20 ms after laparoscopic RDN (95% CI = 0-30, p = 0.004). Compared to the sham group, the RDN group showed significantly reduced AF inducibility [OR (95% CI) = 0.32 (0.13-0.76) and 0.24 (0.11-0.57) with and without VNS, respectively]. After laparoscopic RDN, the duration of inducible AF episodes was significantly shortened from 28 (10-77) s to 7 (3-11) s (p < 0.001). The novel laparoscopic RDN can immediately reduce AF inducibility in a swine model.

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.

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.

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.

Explainable ML models for a deeper insight on treatment decision for localized prostate cancer.

Although there are several decision aids for the treatment of localized prostate cancer (PCa), there are limitations in the consistency and certainty of the information provided. We aimed to better understand the treatment decision process and develop a decision-predicting model considering oncologic, demographic, socioeconomic, and geographic factors. Men newly diagnosed with localized PCa between 2010 and 2015 from the Surveillance, Epidemiology, and End Results Prostate with Watchful Waiting database were included (n = 255,837). We designed two prediction models: (1) Active surveillance/watchful waiting (AS/WW), radical prostatectomy (RP), and radiation therapy (RT) decision prediction in the entire cohort. (2) Prediction of AS/WW decisions in the low-risk cohort. The discrimination of the model was evaluated using the multiclass area under the curve (AUC). A plausible Shapley additive explanations value was used to explain the model's prediction results. Oncological variables affected the RP decisions most, whereas RT was highly affected by geographic factors. The dependence plot depicted the feature interactions in reaching a treatment decision. The decision predicting model achieved an overall multiclass AUC of 0.77, whereas 0.74 was confirmed for the low-risk model. Using a large population-based real-world database, we unraveled the complex decision-making process and visualized nonlinear feature interactions in localized PCa.

Observation, Radiotherapy, or Radical Prostatectomy for Localized Prostate Cancer: Survival Analysis in the United States.

PURPOSE: Contemporary treatment strategies for localized prostate cancer (PCa) have been evolved over time. However, there is little data regarding survival outcomes based on initial treatment by risk group in this new era. This study aims to evaluate survival outcomes among men who underwent observation, radiotherapy, or radical prostatectomy for localized PCa using a population-based cohort. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) prostate with watchful waiting dataset (2010-2016) was used. We included men diagnosed with localized PCa and clinical stage T1c-2cN0M0. Other inclusion criteria were age 50-79 years, prostate-specific antigen (PSA) ≤50 ng/mL, and initial treatment with observation (active surveillance/watchful waiting), radiotherapy, or radical prostatectomy. PCa risk was assessed using the D'Amico classification. The primary endpoint was overall survival. Secondary endpoints included PCa-specific survival. Inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazard regression and competing risk analysis were performed to assess outcomes. RESULTS: After IPTW-adjusting, pseudo-population comprised 521,656 men (observation: 170,428, radiotherapy: 175,628, radical prostatectomy: 175,600) at a median 36.5 month follow-up. Observation demonstrated the lowest 5-year overall survival rate (91.6%) after IPTW-adjusting in comparison to radiotherapy (92.4%) and radical prostatectomy (96.1%, p<0.001). Men who underwent radical prostatectomy had the lowest cumulative PCa-specific and all-cause mortality (p<0.001). Compared to observation, radiotherapy (sub-distribution hazard ratio [sHR], 0.89; 95% CI, 0.81-0.97; p=0.012) and radical prostatectomy (sHR, 0.46; 95% CI, 0.41-0.52; p<.001) had a lower risk of PCa-specific mortality in competing risk analysis after adjustment for all other factors and other-cause death. CONCLUSIONS: Intermediate-term mortality risk in men with localized PCa were lower with active treatments compared to observation-especially for intermediate- and high-risk disease. However, observation represents a safe management strategy in men within the low-risk group.

Robot-assisted radical cystectomy: Where we are in 2023.

Open radical cystectomy (ORC) is associated with high rates of perioperative morbidity and mortality, owing to its extensive surgical nature and the high frequency of multiple co-morbidities among patients. As an alternative, robot-assisted radical cystectomy (RARC) has been increasingly adopted worldwide, being a reliable treatment option that utilizes minimally invasive surgery. Seventeen years have passed since the advent of the RARC, and comprehensive long-term follow-up data are now becoming available. The present review focuses on the current knowledge of RARC in 2023, and analyzes various aspects, including oncological outcomes, peri/post-operative complications, post-operative quality of life (QoL) change, and cost-effectiveness. Oncologically, RARC showed comparable oncological outcomes to ORC. With regard to complications, RARC was associated with lower estimated blood loss, lower intraoperative transfusion rates, shorter length of stay, lower risk of Clavien-Dindo grade III-V complications, and lower 90-day rehospitalization rates than ORC. In particular, RARC with intracorporeal urinary diversion (ICUD) performed by high-volume centers significantly reduced the risk of post-operative major complications. In terms of post-operative QoL, RARC with extracorporeal urinary diversion (ECUD) showed comparable results to ORC, while RARC with ICUD was superior in some respects. As the RARC implementation rate increases and the learning curve is overcome, more prospective studies and randomized controlled trials with large-scale patients are expected to be conducted in the future. Accordingly, sub-group analysis in various groups such as ECUD, ICUD, continent and non-continent urinary diversion, etc. is considered to be possible.

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).

Natural history of incidentally diagnosed prostate cancer after holmium laser enucleation of the prostate.

OBJECTIVES: There is no consensus on the management plan for incidental prostate cancer (IPCa) after holmium laser enucleation of the prostate (HoLEP). This study aims to investigate the natural course of this disease and suggest appropriate treatment in real clinical practice. METHODS: The medical records of a prospective cohort of patients with LUTS/BPH who underwent HoLEP between July 2008 and December 2020 at Seoul National University Hospital were retrospectively reviewed. Patients who underwent HoLEP for palliative purpose of prostate cancer control were excluded. The natural history of IPCa was assessed by the clinician in a descriptive manner for each treatment option. RESULTS: Among 2630 patients, 141 (5.4%) were diagnosed with IPCa after HoLEP. Pathologic T stage and magnetic resonance imaging results were highly associated with the physician's primary treatment decision-making for IPCa. Active surveillance (AS) was performed in 80% of patients, of whom 90% underwent follow-up without intervention, while the remaining 10% underwent deferred active treatment with a median follow-up of 46.3 months due to International Society of Urological Pathology grade group upgrading or increasing core involvement percentage. Meanwhile, 20% of patients underwent immediate active treatment. With a median follow-up period of 88.3 months after treatment, only one of 25 patients had biochemical recurrence. CONCLUSIONS: The incidence of IPCa after HoLEP was 5.4%, and among these, approximately 20% proceeded with immediate definitive therapy and an additional 6% ultimately received definitive therapy within a median of 4 years of AS but showed excellent oncological outcomes.

Feasibility, Safety, and Functional Outcomes of Pelvic Hypothermia Induced Using a Rectal Cooling Device During Robot-Assisted Radical Prostatectomy: A Phase I/II Trial.

Introduction: Radical prostatectomy (RP) is one of the standard treatments for localized prostate cancer. However, in terms of functional outcomes, there are aspects that still need improvements. We designed this prospective phase I/II clinical trial to assess the safety, clinical feasibility, and functional outcomes of hypothermic robot-assisted RP (RARP). Material and Methods: Twenty patients with preoperative total 5-item International Index of Erectile Function scores ≥12 points, scheduled for RARP, were enrolled in the study. Pelvic hypothermia was induced using an endorectal cooling device (BelloCool System). The primary outcome was the completion rate of the planned hypothermic RARP. Secondary outcomes included the drop in neurovascular bundle (NVB) temperature, adverse (including device-related) events, continence, and potency recoveries, and postoperative quality of life. Contemporaneous patients (propensity score-matched for baseline characteristics) who satisfied the inclusion criteria were included in the control group. Results: The completion rate of the planned hypothermic surgery was 100%. The nadir NVB temperature was 24.9 [22.4, 28.2]°C, which was 10.2 [7.0, 13.1]°C lower than the nadir core body temperature. There was no device-related adverse event, and bowel function was well preserved for the whole follow-up period. At 12 months postoperatively, potency and continence recovery rates were higher in the hypothermic group than in the control group (40% vs 15%, p = 0.027 and 95% vs 80%, p = 0.167, respectively). The Kaplan-Meier curve showed faster recovery rate of potency in the hypothermic group (hazard ratios = 3.46, log-rank p < 0.01). Conclusions: Hypothermic RARP using the BelloCool™ endorectal cooling system is safe and feasible. A large-population-based randomized controlled trial is needed to confirm the potential for a benefit in continence and potency recovery.

Sensitive electrochemical sensing platform based on Au nanoflower-integrated carbon fiber for detecting interleukin-6 in human serum.

Prostate cancer (PCa) is the most prevalent cancer worldwide, with a high mortality rate. The early and accurate detection of PCa is critical in reducing mortality and saving lives. Timely diagnosis can improve the chances of successful treatment using advanced technologies. In recent years, nanomaterial-based electrochemical sensing strategies have been adopted in clinical diagnosis, as they allow sensitive early-biomarker detections to be converged with a cost-effective electronic readout system. Herein, we present a flexible electrochemical immunosensor platform for detecting interleukin-6 (IL-6) based on an Au-integrated flexible carbon fiber (Au/CF) electrode prepared via electrodeposition and chemically modified to capture IL-6 antibodies. Several techniques are used to analyze the prepared Au/CF composite electrodes to confirm their morphology, structure, and elemental composition. Under optimum conditions, the fabricated immunosensor exhibits a wide linear dynamic ranging from 1 fg/mL to 1 µg/mL and a low detection limit of 0.056 fg/mL, with a sensitivity of 62.17 µA/(fg mL-1). The proposed fiber-based immunosensor is used to quantify the concentration of IL-6 in serum samples from clinical PCa patients (T3b and T4 stages), and the results are validated using the commercial Meso Scale Diagnostics (MSD) V-Plex method. The acceptable results yielded by the proposed immunosensor indicate that it can serve as a new platform to realize highly sensitive and cost-effective diagnostic strategies for the early diagnosis of PCa.

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.