Highly efficient nucleic acid encapsulation method for targeted gene therapy using antibody conjugation system.

Gene therapy has surfaced as a promising avenue for treating cancers, offering the advantage of deliberate adjustment of targeted genes. Nonetheless, the swift degradation of nucleic acids in the bloodstream necessitates an effective and secure delivery system. The widespread utilization of poly(lactic-co-glycolic acid) (PLGA) nanoparticles as drug delivery systems has highlighted challenges in controlling particle size and release properties. Moreover, the encapsulation of nucleic acids exacerbates these difficulties due to the negatively charged surface of PLGA nanoparticles. In this study, we aimed to improve the encapsulation efficiency of nucleic acids by employing negatively charged microbeads and optimizing the timing of the specific formulation steps. Furthermore, by conjugating PSMA-617, a ligand for the prostate-specific membrane antigen (PSMA), with PLGA nanoparticles, we assessed the antitumor effects and the efficacy of a nucleic acid delivery system on a prostate cancer model. The employed technique within the nucleic acid encapsulation system represents a novel approach that could be adapted to encapsulate various kinds of nucleic acids. Moreover, it enables the attachment of targeting moieties to different cell membrane proteins, thereby unveiling new prospects for precise therapeutics in cancer therapy.

Comprehensive molecular characterization of TFE3-rearranged renal cell carcinoma.

TFE3-rearranged renal cell cancer (tRCC) is a rare form of RCC that involves chromosomal translocation of the Xp11.2 TFE3 gene. Despite its early onset and poor prognosis, the molecular mechanisms of the pathogenesis of tRCC remain elusive. This study aimed to identify novel therapeutic targets for patients with primary and recurrent tRCC. We collected 19 TFE3-positive RCC tissues that were diagnosed by immunohistochemistry and subjected them to genetic characterization to examine their genomic and transcriptomic features. Tumor-specific signatures were extracted using whole exome sequencing (WES) and RNA sequencing (RNA-seq) data, and the functional consequences were analyzed in a cell line with TFE3 translocation. Both a low burden of somatic single nucleotide variants (SNVs) and a positive correlation between the number of somatic variants and age of onset were observed. Transcriptome analysis revealed that four samples (21.1%) lacked the expected fusion event and clustered with the genomic profiles of clear cell RCC (ccRCC) tissues. The fusion event also demonstrated an enrichment of upregulated genes associated with mitochondrial respiration compared with ccRCC expression profiles. Comparison of the RNA expression profile with the TFE3 ChIP-seq pattern data indicated that PPARGC1A is a metabolic regulator of the oncogenic process. Cell proliferation was reduced when PPARGC1A and its related metabolic pathways were repressed by its inhibitor SR-18292. In conclusion, we demonstrate that PPARGC1A-mediated mitochondrial respiration can be considered a potential therapeutic target in tRCC. This study identifies an uncharacterized genetic profile of an RCC subtype with unique clinical features and provides therapeutic options specific to tRCC.

Preoperative smoking and robot-assisted radical cystectomy outcomes & complications in multicenter KORARC database.

To investigate the influence of preoperative smoking history on the survival outcomes and complications in a cohort from a large multicenter database. Many patients who undergo radical cystectomy (RC) have a history of smoking; however, the direct association between preoperative smoking history and survival outcomes and complications in patients with muscle-invasive bladder cancer (MIBC) who undergo robot-assisted radical cystectomy (RARC) remains unexplored. We conducted a retrospective analysis using data from 749 patients in the Korean Robot-Assisted Radical Cystectomy Study Group (KORARC) database, with an average follow-up duration of 30.8 months. The cohort was divided into two groups: smokers (n = 351) and non-smokers (n = 398). Propensity score matching was employed to address differences in sample size and baseline demographics between the two groups (n = 274, each). Comparative analyses included assessments of oncological outcomes and complications. After matching, smoking did not significantly affect the overall complication rate (p = 0.121). Preoperative smoking did not significantly increase the occurrence of complications based on complication type (p = 0.322), nor did it increase the readmission rate (p = 0.076). There were no perioperative death in either group. Furthermore, preoperative smoking history showed no significant impact on overall survival (OS) [hazard ratio (HR) = 0.87, interquartile range (IQR): 0.54-1.42; p = 0.589] and recurrence-free survival (RFS) (HR = 1.12, IQR: 0.83-1.53; p = 0.458) following RARC for MIBC. The extent of preoperative smoking (≤ 10, 10-30, and ≥ 30 pack-years) had no significant influence on OS and RFS in any of the categories (all p > 0.05). Preoperative smoking history did not significantly affect OS, RFS, or complications in patients with MIBC undergoing RARC.

A dietary commensal microbe enhances antitumor immunity by activating tumor macrophages to sequester iron.

Innate immune cells generate a multifaceted antitumor immune response, including the conservation of essential nutrients such as iron. These cells can be modulated by commensal bacteria; however, identifying and understanding how this occurs is a challenge. Here we show that the food commensal Lactiplantibacillus plantarum IMB19 augments antitumor immunity in syngeneic and xenograft mouse tumor models. Its capsular heteropolysaccharide is the major effector molecule, functioning as a ligand for TLR2. In a two-pronged manner, it skews tumor-associated macrophages to a classically active phenotype, leading to generation of a sustained CD8+ T cell response, and triggers macrophage 'nutritional immunity' to deploy the high-affinity iron transporter lipocalin-2 for capturing and sequestering iron in the tumor microenvironment. This process induces a cycle of tumor cell death, epitope expansion and subsequent tumor clearance. Together these data indicate that food commensals might be identified and developed into 'oncobiotics' for a multi-layered approach to cancer therapy.

CREST: phase III study of sasanlimab and Bacillus Calmette-Guérin for patients with Bacillus Calmette-Guérin-naïve high-risk non-muscle-invasive bladder cancer.

Bacillus Calmette-Guérin (BCG) is the standard of care for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT). BCG in combination with programmed cell death-1 (PD-1) inhibitors may yield greater anti-tumor activity compared with either agent alone. CREST is a phase III study evaluating the efficacy and safety of the subcutaneous PD-1 inhibitor sasanlimab in combination with BCG for patients with BCG-naive high-risk NMIBC. Eligible participants are randomized to receive sasanlimab plus BCG (induction ± maintenance) or BCG alone for up to 25 cycles within 12 weeks of TURBT. The primary outcome is event-free survival. Secondary outcomes include additional efficacy end points and safety. The target sample size is around 1000 participants.

Non-muscle-invasive bladder cancer (NMIBC) is the most common type of bladder cancer. Most people have surgery to remove the cancer cells while leaving the rest of the bladder intact. This is called transurethral resection of a bladder tumor (TURBT). For people with high-risk NMIBC, a medicine called Bacillus Calmette-Guérin (BCG) is placed directly inside the bladder after TURBT. A 'high risk' classification means that the cancer is more likely to spread or come back after treatment. Some people's cancer does not respond to BCG or returns after BCG treatment. Researchers are currently looking at whether BCG combined with other immunotherapies may prevent cancer growth more than BCG on its own. Immunotherapy helps the immune system recognize and kill cancer cells. Sasanlimab is an immunotherapy medicine that is not yet approved to treat people with NMIBC. It is given as an injection under the skin. In this CREST study, researchers are looking at how safe and effective sasanlimab plus BCG is for people with high-risk NMIBC. Around 1000 people are taking part in CREST. They must have had TURBT 12 weeks or less before joining the study. Researchers want to know how long people live without certain events occurring, such as bladder cancer cells returning. A plain language summary of this article can be found as Supplementary Material. Clinical Trial Registration: NCT04165317; 2019-003375-19 (EudraCT) (ClinicalTrials.gov).

Controversies in terminology associated with management of BCG-unresponsive NMIBC in Asia-Pacific.

OBJECTIVES: Examine the understanding of terminologies and management patterns of bacillus Calmette-Guérin (BCG)-unresponsive nonmuscle invasive bladder cancer (NMIBC) in six territories in Asia-Pacific. METHODS: This study involved two phases: (1) a survey with 32 urologists and 7 medical oncologists (MOs) and (2) a factorial experiment and in-depth interviews with 23 urologists and 2 MOs. All clinicians had ≥8 years' experience managing NMIBC patients in Australia, Hong Kong, Japan, South Korea, Singapore, and Taiwan. Data from Phase 1 were summarized using descriptive statistics; content and thematic analyses applied in Phase 2. RESULTS: In phase 1, 35% of clinicians defined BCG-unresponsive as BCG-refractory, -relapse and -resistant, 6% defined it as BCG-refractory and -relapse; 22% classified BCG-failure as BCG-refractory, -relapse, -resistant, and when muscle-invasive bladder cancer is detected. If eligible and willing, 50% (interquartile range [IQR], 50%-80%) of BCG-unresponsive patients would undergo radical cystectomy (RC), and 50% (IQR 20%-50%) of RC-eligible patients would receive bladder-sparing treatment or surveillance. In phase 2, we found that 32%, 88%, and 48% of clinicians, respectively, used "BCG-unresponsive," "BCG-refractory," and "BCG-relapse" in clinical practice but with no consistent interpretation of the terms. Compared with EAU definitions, 8%-60% of clinicians appropriately classified 9 tumor types that are persistent or recurrent after adequate BCG. Fifty percent of clinicians mentioned a lack of bladder-preserving treatment that outperforms RC in quality of life as a reason to retreat BCG-unresponsive patients with BCG. CONCLUSIONS: Our study revealed varied understanding and application of BCG-unresponsive terminologies in practice. There is a need for a uniform and simple definition of BCG-unresponsive disease in Asia-Pacific.

Risk stratification and management of non-muscle-invasive bladder cancer: A physician survey in six Asia-Pacific territories.

OBJECTIVES: Multiple clinical practice guidelines, conflicting evidence, and physician perceptions result in variations in risk stratification among patients with non-muscle-invasive bladder cancer (NMIBC). This study aims to describe the extent of this variation and its impact on management approaches in the Asia-Pacific region. METHODS: We conducted a cross-sectional survey involving 32 urologists and seven medical oncologists with ≥8 years of experience managing early-stage bladder cancer patients across Australia, Hong Kong, Japan, South Korea, Singapore, and Taiwan. The physicians completed an anonymous questionnaire that assessed their risk stratification and respective management approaches, based on 19 NMIBC characteristics. For each NMIBC characteristic, they were required to select one risk group, and their most preferred management approach. RESULTS: Our results demonstrated a higher consensus on risk classification versus management approaches. More than 50% of the respondents agreed on the risk classification of all NMIBC characteristics, but 42% or fewer chose the same treatment option as their preferred choice for all but two characteristics-existence of variant histology (55%) and persistent high-grade T1 disease on repeat resection (52%). Across territories, there was the greatest variation in preferred treatment options (i.e., no treatment, intravesical chemotherapy, or Bacillus Calmette-Guérin [BCG] treatment) for intermediate-risk patients and the highest consensus on the treatment of very high-risk patients, namely radical cystectomy. CONCLUSIONS: Our study revealed considerable variation in risk stratification and management of NMIBC in the region. It is critical to develop practical algorithms to facilitate the recognition of NMIBC and standardize the treatment of NMIBC patients.

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.

The effect of goal-directed hemodynamic therapy on clinical outcomes in patients undergoing radical cystectomy: a randomized controlled trial.

BACKGROUND: This study investigated the effects of intraoperative goal-directed hemodynamic therapy (GDHT) on postoperative outcomes in patients undergoing open radical cystectomy. METHODS: This prospective, single-center, randomized controlled trial included 82 patients scheduled for open radical cystectomy between September 2018 and November 2021. The GDHT group (n = 39) received the stroke volume index- and cardiac index-based hemodynamic management using advanced hemodynamic monitoring, while the control group (n = 36) received the standard care under the discretion of attending anesthesiologists during surgery. The primary outcome was the incidence of a composite of in-hospital postoperative complications during hospital stays. RESULTS: A total of 75 patients were included in the final analysis. There was no significant difference in the incidence of in-hospital postoperative complications (28/39 [71.8%] vs. 30/36 [83.3%], risk difference [95% CI], -0.12 [-0.30 to 0.07], P = 0.359) between the groups. The amounts of intraoperative fluid administered were similar between the groups (2700 [2175-3250] vs. 2900 [1950-3700] ml, median difference [95% CI] -200 [-875 to 825], P = 0.714). The secondary outcomes, including the incidence of seven major postoperative complications, duration of hospital stay, duration of intensive care unit stay, and grade of complications, were comparable between the two groups. Trends in postoperative estimated glomerular filtration rate, serum creatinine, and C-reactive protein did not differ significantly between the two groups. CONCLUSIONS: Intraoperative GDHT did not reduce the incidence of postoperative in-hospital complications during the hospital stay in patients who underwent open radical cystectomy. TRIAL REGISTRATION: This study was registered at http://www. CLINICALTRIALS: gov (Registration number: NCT03505112; date of registration: 23/04/2018).

Erdafitinib or Chemotherapy in Advanced or Metastatic Urothelial Carcinoma.

BACKGROUND: Erdafitinib is a pan-fibroblast growth factor receptor (FGFR) inhibitor approved for the treatment of locally advanced or metastatic urothelial carcinoma in adults with susceptible FGFR3/2 alterations who have progression after platinum-containing chemotherapy. The effects of erdafitinib in patients with FGFR-altered metastatic urothelial carcinoma who have progression during or after treatment with checkpoint inhibitors (anti-programmed cell death protein 1 [PD-1] or anti-programmed death ligand 1 [PD-L1] agents) are unclear. METHODS: We conducted a global phase 3 trial of erdafitinib as compared with chemotherapy in patients with metastatic urothelial carcinoma with susceptible FGFR3/2 alterations who had progression after one or two previous treatments that included an anti-PD-1 or anti-PD-L1. Patients were randomly assigned in a 1:1 ratio to receive erdafitinib or the investigator's choice of chemotherapy (docetaxel or vinflunine). The primary end point was overall survival. RESULTS: A total of 266 patients underwent randomization: 136 to the erdafitinib group and 130 to the chemotherapy group. The median follow-up was 15.9 months. The median overall survival was significantly longer with erdafitinib than with chemotherapy (12.1 months vs. 7.8 months; hazard ratio for death, 0.64; 95% confidence interval [CI], 0.47 to 0.88; P = 0.005). The median progression-free survival was also longer with erdafitinib than with chemotherapy (5.6 months vs. 2.7 months; hazard ratio for progression or death, 0.58; 95% CI, 0.44 to 0.78; P<0.001). The incidence of grade 3 or 4 treatment-related adverse events was similar in the two groups (45.9% in the erdafitinib group and 46.4% in the chemotherapy group). Treatment-related adverse events that led to death were less common with erdafitinib than with chemotherapy (in 0.7% vs. 5.4% of patients). CONCLUSIONS: Erdafitinib therapy resulted in significantly longer overall survival than chemotherapy among patients with metastatic urothelial carcinoma and FGFR alterations after previous anti-PD-1 or anti-PD-L1 treatment. (Funded by Janssen Research and Development; THOR ClinicalTrials.gov number, NCT03390504.).

Nivolumab plus Gemcitabine-Cisplatin in Advanced Urothelial Carcinoma.

BACKGROUND: No new agent has improved overall survival in patients with unresectable or metastatic urothelial carcinoma when added to first-line cisplatin-based chemotherapy. METHODS: In this phase 3, multinational, open-label trial, we randomly assigned patients with previously untreated unresectable or metastatic urothelial carcinoma either to receive intravenous nivolumab (at a dose of 360 mg) plus gemcitabine-cisplatin (nivolumab combination) every 3 weeks for up to six cycles, followed by nivolumab (at a dose of 480 mg) every 4 weeks for a maximum of 2 years, or to receive gemcitabine-cisplatin alone every 3 weeks for up to six cycles. The primary outcomes were overall and progression-free survival. The objective response and safety were exploratory outcomes. RESULTS: A total of 608 patients underwent randomization (304 to each group). At a median follow-up of 33.6 months, overall survival was longer with nivolumab-combination therapy than with gemcitabine-cisplatin alone (hazard ratio for death, 0.78; 95% confidence interval [CI], 0.63 to 0.96; P = 0.02); the median survival was 21.7 months (95% CI, 18.6 to 26.4) as compared with 18.9 months (95% CI, 14.7 to 22.4), respectively. Progression-free survival was also longer with nivolumab-combination therapy than with gemcitabine-cisplatin alone (hazard ratio for progression or death, 0.72; 95% CI, 0.59 to 0.88; P = 0.001). The median progression-free survival was 7.9 months and 7.6 months, respectively. At 12 months, progression-free survival was 34.2% and 21.8%, respectively. The overall objective response was 57.6% (complete response, 21.7%) with nivolumab-combination therapy and 43.1% (complete response, 11.8%) with gemcitabine-cisplatin alone. The median duration of complete response was 37.1 months with nivolumab-combination therapy and 13.2 months with gemcitabine-cisplatin alone. Grade 3 or higher adverse events occurred in 61.8% and 51.7% of the patients, respectively. CONCLUSIONS: Combination therapy with nivolumab plus gemcitabine-cisplatin resulted in significantly better outcomes in patients with previously untreated advanced urothelial carcinoma than gemcitabine-cisplatin alone. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 901 ClinicalTrials.gov number, NCT03036098.).

Renal function change after radical cystectomy for urothelial carcinoma patients with a solitary kidney may be independent of urinary diversion type.

PURPOSE: To compare renal function change by urinary diversion (UD) type (ileal conduit [IC] vs. neobladder [NB]) in patients with a single kidney who underwent radical cystectomy (RC) due to bladder cancer. MATERIALS AND METHODS: We evaluated the renal function change in 86 patients with a single kidney who underwent RC between January 1999 and August 2022. Renal function was assessed using serum creatinine, serum estimated glomerular filtration rate (eGFR), eGFR difference value (preoperative and follow-up values), and eGFR difference proportion (eGFR difference value/preoperative eGFR) at 1, 3, 6, 12, 24, 36, 48, and 60 months. In addition, multiple definitions of eGFR decline were evaluated: 10 points, 10%, and 20% decline in eGFR. Cox regression models were used to identify risk factors of eGFR decline-free, recurrence-free, overall, and cancer-specific survival rates. RESULTS: A total of 54 patients (62.8%) underwent IC, whereas 32 (37.2%) underwent NB. Baseline characteristics were similar between the two groups except for age and body mass index. Renal functions over time by various methods did not differ significantly between the IC and NB groups. Furthermore, eGFR decline-free survival rate using different definitions was similar between the IC and NB groups. Overall survival, recurrence-free survival, and cancer-specific-free survival rates were not different between the IC and NB groups. CONCLUSIONS: UD type (IC vs. NB) did not impact the renal function change of patients with a single kidney who underwent RC. Therefore, patients with a single kidney might be considered to be an indication of NB.

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.

Prognostic impact of postoperative neutrophil-to-lymphocyte ratio on survival outcomes of patients treated with radical nephroureterectomy for upper urinary tract urothelial carcinoma: a single institution retrospective analysis using propensity score matching.

Purpose: To investigate the prognostic impact of postoperative neutrophil to lymphocyte ratio (NLR) on survival outcomes in upper urinary tract urothelial carcinoma (UTUC). Materials and methods: Data from 397 patients with UTUC who underwent radical nephroureterectomy (RNU) without a history of neoadjuvant chemotherapy between 2002 and 2017 were retrospectively analyzed. Based on a postoperative NLR cut-off of 3, patients were divided into low NLR (<3) or high NLR (≥ 3) groups. After 2:1 propensity score matching, a Kaplan-Meier with log-rank test was used to compare survival outcomes between the two groups. Univariate and multivariate Cox proportional hazard models were used to investigate the impact of the postoperative NLR on survival outcomes. Results: The matched cohort (n=176) consisted of 116 low NLR and 60 high NLR patients. The Kaplan-Meier curves showed significant differences in the 3- and 5-year overall and cancer-specific survival rates between the two groups (each p = 0.03). Multivariate Cox regression analysis revealed that a postoperative high NLR was an independent predictor of worse overall survival (hazard ratio [HR]:2.13; 95% confidence interval [CI]:1.18-3.85, p = 0.012) and cancer-specific survival (HR:2.16; 95% CI 1.11-4.21, p = 0.024). Conclusions: Propensity score matching analysis revealed postoperative high NLR can be considered a potential inflammatory biomarker for predicting survival outcomes of UTUC patients treated with RNU.

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).

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.