Retrospective Multicenter Analysis of Prognostic Risk Factors for One Year Recurrence in Patient With Renal Cell Carcinoma After Partial or Radical Nephrectomy: Results of Korean Renal Cancer Study Group (KRoCS) Database.

BACKGROUND: We sought to identify prognostic risk factors for one year recurrence in patient with renal cell carcinoma (RCC) after partial or radical nephrectomy. METHODS: We performed a retrospective study of 1,269 patients with RCC after partial or radical nephrectomy and diagnosed recurrence using Korean Renal Cancer Study Group (KRoCS) database between January 1991 and March 2017. Recurrence-free survival (RFS), and overall survival (OS) were calculated using the Kaplan-Meier method and multivariate Cox regression analysis were performed to evaluate independent prognostic factors for recurrence. RESULTS: The median patient age was 56 years and median follow-up period was 67 months. Multivariable analysis demonstrated BMI greater than or equal to 23 and less than 30 (vs. BMI less than 23, hazard ratio [HR]: 0.707, P = 0.020) reduced recurrence one year postoperatively. Eastern Cooperative Oncology Group performance status (ECOG PS) greater than or equal to 1 (vs. ECOG PS 0, HR: 1.548, P = 0.007), high pathological T stage (pT2 vs. pT1, HR: 2.622, P < 0.001; pT3 vs. pT1, HR: 4.256, P < 0.001; pT4 vs. pT1, HR: 4.558, P < 0.001), and tumor necrosis (vs. no tumor necrosis, HR: 2.822, P < 0.001) were independent predictive factors for early recurrence within one year in patients with RCC. Statistically significant differences on RFS and OS were found among pathological T stages (pT2 vs. pT1; pT3 vs. pT1; pT4 vs. pT1, all P < 0.001). CONCLUSION: This large multicenter study demonstrated ECOG PS greater than or equal to 1, high pathological T stage, tumor necrosis and BMI less than 23 were significant prognostic risk factors of early recurrence within one year in patients with RCC who underwent nephrectomy.

Clinical Significance of Radical Prostatectomy in Clinical Lymph Node Metastasis in Prostate Cancer.

BACKGROUND: This study aimed to investigate the role of radical prostatectomy (RP) among clinical nodal metastasis prostate cancer and whether histological confirmation of lymph node metastasis through surgery can help with treatment. PATIENTS AND METHODS: After excluding patients with distant metastatic prostate cancer or neoadjuvant androgen deprivation therapy, 42 patients with clinical nodal metastasis who underwent RP at our institution were included in the study. We classified them as having or not having pathological lymph node metastasis. Clinicopathologic data were analyzed in this retrospective chart review. Kaplan-Meier analysis was used to calculate the estimated castration-resistant prostate cancer (CRPC)-free survival, biochemical recurrence (BCR)-free survival, and cancer-specific survival (CSS). RESULTS: There is no significant difference in age, presence of diabetes mellitus, hypertension, BCR time, CRPC time, overall survival, salvage RT rate, and initial prostate-specific antigen level between the two groups. However, there is a significant difference in the pathology N1 group in terms of pathological T stage, pathologic Gleason score, BCR rate, CRPC rate, and CSS. A multivariate Cox proportional hazard regression analysis was used to identify predictors of CRPC-free survival. Patients with pathological lymph node metastasis had a shorter CRPC-free survival [hazard ratio (HR) 4.87; 95% confidence interval (CI) 1.25-19.00, p = 0.02]. CONCLUSION: Radical prostatectomy can confirm lymph node metastasis. Although pathologic diagnosis has no effect on time to BCR and CPRC, because it affects BCR rate, CRPC rate, and CSS, an accurate pathological diagnosis obtained through surgery is beneficial in the treatment of clinical lymph node metastasis prostate cancer.

Outbred Mice with Streptozotocin-Induced Diabetes Show Sex Differences in Glucose Metabolism.

Outbred mice (ICR) with different genotypes and phenotypes have been reported to be more suitable for scientific testing than inbred mice because they are more similar to humans. To investigate whether the sex and genetic background of the mice are important factors in the development of hyperglycemia, we used ICR mice and divided them into male, female, and ovariectomized female (FOVX) groups and treated them with streptozotocin (STZ) for five consecutive days to induce diabetes. Our results show that fasting blood glucose and hemoglobin A1c (HbA1c) levels were significantly higher in diabetes-induced males (M-DM) and ovariectomized diabetes-induced females (FOVX-DM) than in diabetes-induced females (F-DM) at 3 and 6 weeks after STZ treatment. Furthermore, the M-DM group showed the most severe glucose tolerance, followed by the FOVX-DM and F-DM groups, suggesting that ovariectomy affects glucose tolerance in female mice. The size of pancreatic islets in the M-DM and FOVX-DM groups was significantly different from that of the F-DM group. The M-DM and FOVX-DM groups had pancreatic beta-cell dysfunction 6 weeks after STZ treatment. Urocortin 3 and somatostatin inhibited insulin secretion in the M-DM and FOVX-DM groups. Overall, our results suggest that glucose metabolism in mice is dependent on sex and/or genetic background.

Association Between Sarcopenia and Survival of Patients with Organ-Confined Renal Cell Carcinoma after Radical Nephrectomy.

BACKGROUND: We aimed to describe the effect of preoperative sarcopenia on oncologic outcomes of organ-confined renal cell carcinoma (RCC) after radical nephrectomy. PATIENTS AND METHODS: A total of 632 patients with pT1-2 RCC who underwent radical nephrectomy between 2004 and 2014 were retrospectively analyzed. From preoperative computerized tomography (CT) scans, skeletal muscle index (SMI) was measured and gender-specific cutoff values at third lumbar vertebra of 52.4 cm2/m2 for men and 38.5 cm2/m2 for women were used to define sarcopenia. Survivals were compared and associations with sarcopenia were analyzed using Kaplan-Meier log rank tests and Cox proportional hazard regression models. Median follow-up was 83 months. RESULTS: Of 632 patients, 268 (42.4%) were classified as sarcopenic. The sarcopenic group was more advanced in age (57 versus 53 years) and more predominantly male (71.3% versus 59.9%). Sarcopenic patients had lower body mass index (BMI, 23.0 versus 25.9 kg/m2), but there was no difference in tumor size, stage, or nuclear grade. Sarcopenia was associated with poorer overall survival (OS) and cancer-specific survival (CSS; OS 94.0% versus 82.1%; p < 0.001 and CSS 97.5% versus 91.8%; p < 0.001). On multivariate analysis, sarcopenia was an independent risk factor for all-cause mortality [hazard ratio (HR) 2.58; 95% CI 1.02-6.54] and cancer-specific mortality (HR 3.07; 95% CI 1.38-6.83). CONCLUSIONS: Sarcopenia at diagnosis was an independent risk factor for all-cause and cancer-specific mortality after radical nephrectomy for pT1-2 RCC. These findings underscore the importance of assessing presence of sarcopenia for risk stratification even among surgical candidates.

Efficacy of the Treatment of Intraperitoneal Bladder Perforation during Transurethral Resection of Bladder Tumor with the Urethral Catheter Alone: Retrospective Analysis of over 15 Years Using the Clinical Data Warehouse System.

INTRODUCTION: We investigated the efficacy of a urethral catheter alone for intraperitoneal perforation during transurethral resection of bladder tumor (TURBT). PATIENTS AND METHODS: We retrospectively evaluated the medical records of 4,543 patients who underwent TURBT from January 2000 to December 2017 using the Clinical Data Warehouse system. The clinicopathologic characteristics, recurrence-free survival, and progression-free survival were compared between the patient groups with intraperitoneal perforation treated with the Foley catheter alone, extraperitoneal perforation, and matched control TURBT. RESULTS: Intraperitoneal perforation and extraperitoneal perforation were observed in 16 (35.6%) and 29 (64.4%) patients, respectively. In the intraperitoneal perforation group, 11 (68.8%), 2 (12.5%), and 3 (18.8%) patients were treated with the Foley catheter alone, additional percutaneous drainage, and delayed open surgery, respectively. The use of the Foley catheter alone in patients with intraperitoneal perforation of smaller size than the cystoscope or no pelvic radiotherapy history showed improved efficacy without sequelae or therapeutic delay. One of the 2 patients with the size of the intraperitoneal perforation larger than the cystoscope was successfully treated with the Foley catheter alone, whereas the other patient underwent delayed surgical repair. There was no difference in recurrence-free survival and progression-free survival of the intraperitoneal perforation treated with the Foley catheter alone compared to those of the matched control TURBT (p = 0.909, p = 0.518) and the extraperitoneal perforation (p = 0.458, p = 0.699). CONCLUSIONS: Intraperitoneal perforation rarely occurred during TURBT. In the case of intraperitoneal perforation of size smaller than cystoscopy or without pelvic radiotherapy history, treatment with the Foley alone showed successful improvement and safe oncological results. Therefore, treatment with the urethral catheter alone can be carefully considered when an intraperitoneal perforation smaller than the cystoscope size or without pelvic radiotherapy history occurs.

Optimal high-density lipoprotein cholesterol level for decreasing benign prostatic hyperplasia in men not taking statin medication: A historical cohort study.

BACKGROUND: We evaluated the optimal high-density lipoprotein cholesterol level for benign prostatic hyperplasia (BPH) prevention in men not taking statin medication using a large historical cohort. METHODS: We initially selected 130 454 men who underwent health checkups in 2009 from the National Health Information Database of the National Health Insurance Service. After excluding 36 854 men with BPH in 2009, and 45 061 men for statin use, 48 539 men were ultimately included in the analysis. A Kaplan-Meier analysis and multivariable Cox regression analysis was performed to assess the optimal high-density lipoprotein cholesterol level for preventing BPH. RESULTS: High-density lipoprotein cholesterol levels were less than 40 mg/dL in 7431 (15.3%) men, 40 to 49 in 15 861 (32.7%), 50 to 59 in 15 328 (27.5%), and greater than or equal to 60 in 11 919 (24.6%). The overall cumulative incidence of BPH was 4.4%, 8.7%, 13.0%, and 17.8% at the 1-, 2-, 3-, and 4-year follow-up periods, respectively. In multivariable analysis, high-density lipoprotein greater than or equal to 60 mg/dL were significantly associated with a decreased incidence of BPH, as were age, residence, income, body mass index, diabetes, hypertension, triglyceride, and increased annual clinic visits, especially in men in their 40s. CONCLUSION: Elevated serum high-density lipoprotein cholesterol levels were negatively associated with BPH incidence. In addition, maintaining high-density lipoprotein greater than or equal to 60 mg/dL was associated with a decreased BPH incidence compared with high-density lipoprotein less than 40 mg/dL, especially in men in their 40s.

Development and validation of an explainable artificial intelligence-based decision-supporting tool for prostate biopsy.

OBJECTIVES: To develop and validate a risk calculator for prostate cancer (PCa) and clinically significant PCa (csPCa) using explainable artificial intelligence (XAI). PATIENTS AND METHODS: We used data of 3791 patients to develop and validate the risk calculator. We initially divided the data into development and validation sets. An extreme gradient-boosting algorithm was applied to the development calculator using five-fold cross-validation with hyperparameter tuning following feature selection in the development set. The model feature importance was determined based on the Shapley value. The area under the curve (AUC) of the receiver operating characteristic curve was analysed for each validation set of the calculator. RESULTS: Approximately 1216 (32.7%) and 562 (14.8%) patients were diagnosed with PCa and csPCa. The data of 2843 patients were used for development, whereas the data of 948 patients were used as a test set. We selected the variables for each PCa and csPCa risk calculation according to the least absolute shrinkage and selection operator regression. The AUC of the final PCa model was 0.869 (95% confidence interval [CI] 0.844-0.893), whereas that of the csPCa model was 0.945 (95% CI 0.927-0.963). The prostate-specific antigen (PSA) level, free PSA level, age, prostate volume (both the transitional zone and total), hypoechoic lesions on ultrasonography, and testosterone level were found to be important parameters in the PCa model. The number of previous biopsies was not associated with the risk of csPCa, but was negatively associated with the risk of PCa. CONCLUSION: We successfully developed and validated a decision-supporting tool using XAI for calculating the probability of PCa and csPCa prior to prostate biopsy.

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

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.

Silk Fibroin Promotes the Regeneration of Pancreatic ß-Cells in the C57BL/KsJ-Leprdb/db Mouse.

Diabetes mellitus is a chronic metabolic disease, and its progression leads to serious complications. Although various novel therapeutic approaches for diabetes mellitus have developed in the last three decades, its prevalence has been rising more rapidly worldwide. Silk-related materials have been used as anti-diabetic remedies in Oriental medicine and many studies have shown the effects of silk fibroin (SF) in both in vitro and in vivo models. In our previous works, we reported that hydrolyzed SF improved the survival of HIT-T15 cells under high glucose conditions and ameliorated diabetic dyslipidemia in a mouse model. However, we could not provide a precise molecular mechanism. To further evaluate the functions of hydrolyzed SF on the pancreatic ß-cell, we investigated the effects of hydrolyzed SF on the pancreatic ß-cell proliferation and regeneration in the mouse model. Hydrolyzed SF induced the expression of the proliferating cell nuclear antigen (PCNA) and reduced the apoptotic cell population in the pancreatic islets. Hydrolyzed SF treatment not only induced the expression of transcription factors involved in the pancreatic ß-cell regeneration in RT-PCR results but also increased neurogenin3 and Neuro D protein levels in the pancreas of those in the group treated with hydrolyzed SF. In line with this, hydrolyzed SF treatment generated insulin mRNA expressing small cell colonies in the pancreas. Therefore, our results suggest that the administration of hydrolyzed SF increases the pancreatic ß-cell proliferation and regeneration in C57BL/KsJ-Leprdb/db mice.

Comparison of N-methyl-D-aspartate receptor subunit 1 and 4-hydroxynonenal in the hippocampus of natural and chemical-induced aging accelerated mice.

In this study, we compared N-methyl-D-aspartate receptor type 1 (NMDAR1) and 4-hydroxynonenal (4-HNE) in the hippocampus of D-galactose (D-gal)-induced and naturally aging models of mice. These markers represent general phenotypes in aging, and they allowed us to examine the possibility of D-gal as a chemical model agent for aging. We observed an age-dependent reduction of NMDAR1 and an increase in 4-HNE in the dentate gyrus, CA1, and CA3 regions of the hippocampus via immunohistochemistry and western blot analyses. In the D-gal-induced chemical aging model, we observed similar changes in NMDAR1 and 4-HNE although the degree of reduction/increase in NMDAR1/4-HNE was not as severe as that in the naturally aged mice. These results suggest that the D-gal-induced aging model is comparable to naturally aged mice and may be useful for studies of the aging hippocampus.

Privacy-Preserving Prediction of Postoperative Mortality in Multi-Institutional Data: Development and Usability Study.

BACKGROUND: To circumvent regulatory barriers that limit medical data exchange due to personal information security concerns, we use homomorphic encryption (HE) technology, enabling computation on encrypted data and enhancing privacy. OBJECTIVE: This study explores whether using HE to integrate encrypted multi-institutional data enhances predictive power in research, focusing on the integration feasibility across institutions and determining the optimal size of hospital data sets for improved prediction models. METHODS: We used data from 341,007 individuals aged 18 years and older who underwent noncardiac surgeries across 3 medical institutions. The study focused on predicting in-hospital mortality within 30 days postoperatively, using secure logistic regression based on HE as the prediction model. We compared the predictive performance of this model using plaintext data from a single institution against a model using encrypted data from multiple institutions. RESULTS: The predictive model using encrypted data from all 3 institutions exhibited the best performance based on area under the receiver operating characteristic curve (0.941); the model combining Asan Medical Center (AMC) and Seoul National University Hospital (SNUH) data exhibited the best predictive performance based on area under the precision-recall curve (0.132). Both Ewha Womans University Medical Center and SNUH demonstrated improvement in predictive power for their own institutions upon their respective data's addition to the AMC data. CONCLUSIONS: Prediction models using multi-institutional data sets processed with HE outperformed those using single-institution data sets, especially when our model adaptation approach was applied, which was further validated on a smaller host hospital with a limited data set.

Effect of perioperative tamsulosin on successful ureteral access sheath placement and stent-related symptom relief: A double-blinded, randomized, placebo-controlled study.

PURPOSE: This study investigated the effect of administering tamsulosin before surgery on the successful insertion of a 12/14 French (F) ureteral access sheath (UAS) during the procedure, as well as the impact of preoperative and postoperative tamsulosin use on symptoms related to the ureteral stent. MATERIALS AND METHODS: This study was a randomized, single-center, double-blinded, placebo-controlled trial involving 200 patients who underwent unilateral retrograde intrarenal surgery. Patients received either tamsulosin (0.4 mg) or placebo 1 week before surgery until stent removal. Patients were randomly assigned to one of four groups. Group 1 received tamsulosin throughout the study period. Group 2 received tamsulosin before surgery and placebo after surgery. Group 3 received placebo before surgery and tamsulosin after surgery. Group 4 received placebo before and after surgery. The USSQ (Ureteral Stent Symptom Questionnaire) was completed between postoperative days 7 and 14 immediately before stent removal. RESULTS: A total of 160 patients were included in this analysis. Their mean age was 55.0±11.0 years, and 48 patients (30.0%) were female. In the group that received preoperative tamsulosin, the success rate of 12/14F UAS deployment was significantly higher than that of the preoperative placebo group (88.0 vs. 75.3%, p=0.038). Preoperative and postoperative tamsulosin did not significantly alleviate symptoms related to the ureteral stent. CONCLUSIONS: Our results revealed that preoperative administration of tamsulosin improved the success of larger-sized UAS, whereas preoperative and postoperative tamsulosin use did not significantly alleviate symptoms related to ureteral stents.

Preoperative C-reactive protein to albumin ratio as a novel prognostic biomarker for the oncological outcomes of radical nephroureterectomy.

PURPOSE: This study aimed to evaluate the prognostic impact of the preoperative C-reactive protein to albumin ratio (CAR) on progression-free survival (PFS) and cancer-specific survival (CSS) in patients with upper urinary tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). METHODS: A retrospective analysis was conducted using data from a single-center nephroureterectomy registry between January 2011 and December 2017. Participants were categorized into high and low CAR groups based on the optimal CAR cut-off value determined using the Youden index. The primary endpoint was PFS, the time from RNU to metastasis or disease recurrence. The secondary endpoint was CSS, the time from RNU to UTUC-related death. Median PFS and CSS were compared between the high and low CAR groups using Kaplan-Meier analysis and log-rank test. Multivariable Cox proportional hazard regression analysis was performed to assess the prognostic significance of CAR, adjusting for known prognostic factors. RESULTS: We included 491 patients with UTUC in the analysis. The optimal CAR cut-off value was determined to be 0.036, which resulted in classifying 49.3% (242/491) of patients into the high CAR group. The high CAR group had older patients (69.8 vs. 67.4, p-value = 0.01), advanced T and N stages (p-value<0.001), high-grade tumor (p-value = 0.03), and a higher incidence of preoperative hydronephrosis (p-value < 0.01) than the low CAR group. The high CAR group demonstrated significantly inferior median PFS (78.3 vs. 100.3 months, p-value < 0.01) and CSS (73.2 vs. 96.1 months, p-value < 0.01) than the low CAR group. Moreover, high CAR independently increased the risk of disease progression (hazard ratio [HR]: 1.80, 95% confidence interval [CI]: 1.23-2.64, p < 0.01) and UTUC-related mortality (HR: 1.79, 95% CI: 1.15, p < 0.01). CONCLUSION: Pre-operative CAR is independently associated with poor PFS and CSS in patients with UTUC undergoing RNU. Moreover, CAR may be an independent UTUC prognostic factor, offering a cost-effective and minimally invasive marker. However, further validation through large-scale, multi-center studies is necessary to confirm these findings and determine the optimal CAR cut-off value.

Effectiveness of Adjuvant Chemotherapy in Variant Histology Upper Tract Urothelial Carcinoma Following Radical Nephroureterectomy: Stabilized Inverse Probability Treatment Weighting Analysis of Single Center Experience.

PURPOSE: The study aimed to investigate the impact of adjuvant chemotherapy on time to recurrence (TTR) and overall survival (OS) in patients with histologic variants of upper tract urothelial carcinoma (VUTUC) following radical nephroureterectomy (RNU). MATERIALS AND METHODS: A retrospective review of 131 VUTUC patients' medical records, from a pool of 368 non-metastatic localized or locally advanced UTUC cases, treated at a single tertiary referral center between January 2011 and January 2021. The intervention was adjuvant chemotherapy administration post-RNU. TTR and OS were evaluated using Kaplan-Meier and Cox proportional hazard regression, covariates adjusted for age, postoperative GFR, history of neoadjuvant chemotherapy, T and N stage with stabilized inverse probability of treatment weighting (sIPTW). RESULTS: The application of adjuvant chemotherapy showed a significant extension in TTR (P = .01), but no substantial impact on OS (P = .19) after sIPTW adjustment for covariates. Multivariate analysis revealed adjuvant chemotherapy, tumor size, and lymphovascular invasion as significant prognostic factors for TTR. In contrast, only tumor size and perineural invasion were significant for OS. Adjuvant chemotherapy reduced the progression risk in certain VUTUC subtypes (squamous or glandular/micropapillary), but not in sarcomatoid variants. CONCLUSIONS: Adjuvant chemotherapy appears to improve TTR, albeit without a significant effect on OS, in nonmetastatic localized and locally advanced VUTUC patients post-RNU. While beneficial to some VUTUC subtypes, it did not yield significant advantages for sarcomatoid variants. Despite adjustments for known confounders, the study's findings may be subject to potential selection bias and unmeasured confounding factors.

Bilateral Seminal Vesicle Invasion as a Strong Prognostic Indicator in T3b Prostate Cancer Patients Following Radical Prostatectomy: A Comprehensive, Multicenter, Long-term Follow-up Study.

PURPOSE: Pathologic T3b (pT3b) prostate cancer, characterized by seminal vesicle invasion (SVI), exhibits variable oncological outcomes post-radical prostatectomy (RP). Identifying prognostic factors is crucial for patient-specific management. This study investigates the impact of bilateral SVI on prognosis in pT3b prostate cancer. MATERIALS AND METHODS: We evaluated the medical records of a multi-institutional cohort of men who underwent RP for prostate cancer with SVI between 2000 and 2012. Univariate and multivariable analyses were performed using Kaplan-Meier analysis and covariate-adjusted Cox proportional hazard regression for biochemical recurrence (BCR), clinical progression (CP), and cancer-specific survival (CSS). RESULTS: Among 770 men who underwent RP without neo-adjuvant treatment, median follow-up was 85.7 months. Patients with bilateral SVI had higher preoperative prostate-specific antigen levels and clinical T category (all p < 0.001). Extracapsular extension, tumor volume, lymph node metastasis (p < 0.001), pathologic Gleason grade group (p < 0.001), and resection margin positivity (p < 0.001) were also higher in patients with bilateral SVI. The 5-, 10-, and 15-year BCR-free survival rates were 23.9%, 11.7%, and 8.5%; CP-free survival rates were 82.8%, 62.5%, and 33.4%; and CSS rates were 96.4%, 88.1%, and 69.5%, respectively. The bilateral SVI group demonstrated significantly lower BCR-free survival rates, CP-free survival rates, and CSS rates (all p < 0.001). Bilateral SVI was independently associated with BCR (hazard ratio, 1.197; 95% confidence interval, p=0.049), CP (p=0.022), and CSS (p=0.038) in covariate-adjusted Cox regression. CONCLUSION: Bilateral SVI is a robust, independent prognostic factor for poor oncological outcomes in pT3b prostate cancer.

Intravesical instillation-based mTOR-STAT3 dual targeting for bladder cancer treatment.

BACKGROUND: Recent intravesical administration of adenoviral vectors, either as a single injection or in combination with immune checkpoint inhibitors, exemplified by cretostimogene grenadenorepvec and nadofaragene firadenovec, has demonstrated remarkable efficacy in clinical trials for non-muscle invasive bladder cancer. Despite their ability to induce an enhanced immune reaction within the lesion, the intracellular survival signaling of cancer cells has not been thoroughly addressed. METHODS: An analysis of the prognostic data revealed a high probability of therapeutic efficacy with simultaneous inhibition of mTOR and STAT3. Considering the challenges of limited pharmaco-accessibility to the bladder due to its pathophysiological structure and the partially undruggable nature of target molecules, we designed a dual siRNA system targeting both mRNAs. Subsequently, this dual siRNA system was encoded into the adenovirus 5/3 (Ad 5/3) to enhance in vivo delivery efficiency. RESULTS: Gene-targeting efficacy was assessed using cells isolated from xenografted tumors using a single-cell analysis system. Our strategy demonstrated a balanced downregulation of mTOR and STAT3 at the single-cell resolution, both in vitro and in vivo. This approach reduced tumor growth in bladder cancer xenograft and orthotopic animal experiments. In addition, increased infiltration of CD8+ T cells was observed in a humanized mouse model. We provided helpful and safe tissue distribution data for intravesical therapy of siRNAs coding adenoviruses. CONCLUSIONS: The bi-specific siRNA strategy, encapsulated in an adenovirus, could be a promising tool to augment cancer treatment efficacy and overcome conventional therapy limitations associated with "undruggability." Hence, we propose that dual targeting of mTOR and STAT3 is an advantageous strategy for intravesical therapy using adenoviruses.

Risk factors for failing to complete gemcitabine-cisplatin neoadjuvant chemotherapy in muscle invasive bladder cancer patients.

PURPOSE: We evaluated the risk factors associated with failure to complete gemcitabine-cisplatin (GP) neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: In total, 231 patients with MIBC treated with NAC before undergoing radical cystectomy between 2013 and 2022 participated in this study. Logistic regression analysis was performed to assess the relationship between the likelihood of incomplete NAC and clinical and demographic variables, including age, sex, hypertension (HTN), diabetes mellitus (DM), prechemotherapy glomerular filtration rate, clinical T stage, clinical N stage, and body mass index (BMI). RESULTS: Of 231 patients, 209 (90.5%) and 22 (9.5%) completed and discontinued the NAC course, respectively. The mean age was 66.13±9.15, 65.63±9.07, and 70.86±8.66 years for the total sample, continuation, and discontinuation groups, respectively (p=0.010). No significant inter-group differences in sex, HTN, height, weight, BMI, pre-chemotherapy glomerular filtration rate, clinical T stage, or clinical N stage were observed. According to the results of the multivariable analysis, age (odds ratio [OR] 1.076, 95% confidence interval [CI] 1.013-1.143, p=0.018) and the presence of DM (OR 2.541, 95% CI 1.028-6.281, p=0.043) were significantly associated with NAC discontinuation. CONCLUSIONS: Thus, older age and presence of DM are potential risk factors for GP NAC discontinuation in patients with MIBC. Further studies are required to validate our findings and develop strategies to minimize the rate of GP NAC discontinuation in this population.

Association of preoperative sarcopenia with the long-term prognosis of patients with bladder cancer undergoing radical cystectomy.

PURPOSE: This retrospective study aimed to assess the correlation between preoperative sarcopenia and long-term oncologic outcomes in patients undergoing radical cystectomy for bladder cancer. METHODS: We included 528 patients who underwent radical cystectomy for bladder cancer between 2000 and 2010 at Asan Medical Center, Seoul, Korea. Preoperative skeletal muscle mass was quantified by analyzing computed tomography images at the third lumbar vertebra. Sarcopenia was defined based on the skeletal muscle index. We evaluated various clinical and pathological factors to analyze the association between sarcopenia and long-term oncologic outcomes. RESULTS: The median follow-up time was 104 months. Sarcopenia was identified in 37.9% of the patients. Although no significant differences were observed in traditional pathological factors between the sarcopenic and non-sarcopenic groups, sarcopenia was significantly associated with worse oncologic outcomes. Compared to the non-sarcopenic groups, the sarcopenic group had lower overall survival rates (52.0% vs. 67.1% at 5 years, 35.5% vs. 52.7% at 10 years) and higher cancer-specific mortality (63.3% vs. 74.3% at 5 years, 50.7% vs. 67.4% at 10 years). Multivariable Cox regression analysis demonstrated that sarcopenia was an independent predictor of cancer-specific survival (hazard ratio: 1.49, 95% confidence interval: 1.11-2.01, p = 0.008), alongside body mass index, tumor stage, lymph node metastasis, and lymphovascular invasion. CONCLUSION: Sarcopenia was significantly associated with poor cancer-specific survival in patients undergoing radical cystectomy for bladder cancer. Detecting sarcopenia may assist in preoperative risk stratification and long-term management after radical cystectomy.

Comparison of digital and analog [68Ga]Ga-PSMA-11 PET/CT for detecting post-prostatectomy biochemical recurrence in prostate cancer patients: a prospective study.

Digital positron emission tomography/computed tomography (PET/CT) has shown enhanced sensitivity and spatial resolution compared with analog PET/CT. The present study compared the diagnostic performance of digital and analog PET/CT with [68Ga]Ga-PSMA-11 in prostate cancer patients who experienced biochemical recurrence (BCR) after prostatectomy. Forty prostate cancer patients who experienced BCR, defined as serum prostate-specific antigen (PSA) concentrations exceeding 0.2 ng/mL after prostatectomy, were prospectively recruited. These patients were stratified into three groups based on their serum PSA levels. [68Ga]Ga-PSMA-11 was injected into each patient, and images were acquired using both analog and digital PET/CT scanners. Analog and digital PET/CT showed comparable lesion detection rate (71.8% vs. 74.4%), sensitivity (85.0% vs. 90.0%), and positive predictive value (PPV, 100.0% vs. 100.0%). However, digital PET/CT detected more lesions (139 vs. 111) and had higher maximum standardized uptake values (SUVmax, 14.3 vs. 10.3) and higher kappa index (0.657 vs. 0.502) than analog PET/CT, regardless of serum PSA levels. On both analog and digital PET/CT, lesion detection rates and interrater agreement increased with increasing serum PSA levels. Compared with analog PET/CT, digital PET/CT detected more lesions with a higher SUVmax and better interrater agreement in prostate cancer patients who experienced BCR after prostatectomy.

Survival pattern of metastatic renal cell carcinoma patients according to WHO/ISUP grade: a long-term multi-institutional study.

The World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading of renal cell carcinoma (RCC) is classified from grade 1-4, regardless of subtype. The National Comprehensive Cancer Network (NCCN) guidelines (2022) state that if there is an adverse pathological feature, such as grade 3 or higher RCC in stage 1 patients, more rigorous follow-up imaging is recommended. However, the RCC guidelines do not provide specific treatment or follow-up policies by tumor grade. Therefore, this study attempted to find out whether tumor grade affects survival rates in patients with metastatic RCC. The Korean Renal Cancer Study Group (KRoCS) database includes 3108 patients diagnosed with metastatic RCC between September 1992 and February 2017, with treatment methods, progression, and survival data collected from 11 tertiary hospitals. To obtain information on survival rates or causes of death, we utilized the Korea National Statistical Office database and institutional medical records. Data were accessed for research purpose on June, 2023. We then reviewed these sources to gather comprehensive and reliable data on the outcomes of our study cohort. This database was retrospectively analyzed, and out of 3108 metastatic RCC patients, 911 had been identified as WHO/ISUP grade. Grades were classified into either a low-grade (WHO/ISUP grade 1-2) or a high-grade group (WHO/ISUP grade 3-4). The patients were then analyzed related to progression and overall survival (OS). In metastatic clear cell RCC patients, the 1-year OS rate was 69.4% and the median OS was 17.0 months (15.5-18.5) followed up to 203.6 months. When comparing the patient groups, 119 low-grade and 873 high-grade cases were identified. No baseline difference was observed between the two groups, except that the high-grade group had a higher ECOG 1 ratio of 50.4% compared with 34.5% for the low-grade group (p = 0.009). There was a significant difference in OS between high-grade and low-grade groups. OS was 16.0 months (14.6-17.4) in the high-grade group and 28.0 months (21.1-34.9) in the low-grade group (p < 0.001). However, there was no difference in progression-free survival (PFS) rates with 9.0 months (8.0-10.0) for the high-grade group and 10.0 months (6.8-13.2) for the low-grade group (p = 0.377) in first-line treatment. In multivariable analysis, WHO/ISUP grade was a risk factor (HR = 1.511[1.135-2.013], p = 0.005) that influenced the OS. In conclusion, WHO/ISUP grade is a major data source that can be used as a ubiquitous marker of metastatic RCC in pre-IO era. Depending on whether the RCC is high or low grade, the follow-up schedule will need to be tailored according to grade, with higher-grade patients needing more active treatment as it can not only affect the OS in the previously known localized/locoregional recurrence but also the metastatic RCC patient.