Single-port robot-assisted pyeloplasty using the da vinci SP system versus multiport pyeloplasty: Comparison of outcomes and costs.

OBJECTIVE: To investigate the feasibility of single-port (SP) robotic pyeloplasty by comparing perioperative outcomes with those of multiport (MP) robotic pyeloplasty. MATERIALS AND METHODS: We reviewed the data from patients who underwent robot-assisted pyeloplasty for ureteropelvic junction obstruction (UPJO) at a single tertiary institution between March 2016 and May 2022. Radiographic and symptomatic improvements were assessed 3 months postoperatively. Propensity score matching was performed for age, sex, body mass index, and hydronephrosis grade. RESULTS: Of the 15 S P-pyeloplasty and 28 MP-pyeloplasty cases, 14 from each group were matched using 1:1 matching. The SP group had shorter console and operative times without significant differences. Blood loss was lower in the SP group than in the MP group (p = 0.019). The length of hospital stay, opioid use on the operative day, and pain score at discharge did not differ between the two groups. The mean cost for surgery was higher in the SP group than in the MP group (p < 0.001). The mean cost of hospitalization was comparable between the two groups (p = 0.083). The cosmetic numerical rating scale scores were significantly higher in the SP group (p = 0.014). Symptoms improved in all patients, and the radiographic improvement rates were 92.9% in the SP group and 100% in the MP group. CONCLUSION: SP-pyeloplasty showed cosmetic benefits, lower blood loss, operative time, and console time compared with MP-pyeloplasty. In patients who underwent surgery for UPJO for the first time, SP surgery can show comparable outcomes when compared to MP surgery.

ctDNA predicts clinical T1a to pathological T3a upstaging after partial nephrectomy.

Most patients diagnosed with clear cell renal cell carcinoma (ccRCC) are also detected with small and organ-confined tumors, and the majority of these are classified as clinical tumor stage 1a (cT1a). A considerable proportion of patients with cT1 RCC shows tumor upstaging to pathological stage 3a (pT3a), and these patients have worse oncological outcomes. The role of circulating tumor DNA (ctDNA) in RCC has been limited to monitoring treatment response and resistance. Therefore, the present study aimed to evaluate the potential of ctDNA in predicting pT3a upstaging in cT1a ccRCC. We sequenced plasma samples preoperatively collected from 48 patients who had undergone partial nephrectomy for cT1a ccRCC using data from a prospective cohort RCC. The ctDNA were profiled and compared with clinicopathological ccRCC features to predict pT3a upstaging. Associations between ctDNA, tumor complexity, and pT3a upstaging were evaluated. Tumor complexity was assessed using the anatomical classification system. Univariate analysis used chi-squared and Student's t-tests; multivariate analysis considered significant factors from univariate analyses. Of the 48 patients with cT1a ccRCC, 12 (25%) were upstaged to pT3a, with ctDNA detected in 10 (20.8%), predominantly in patients with renal sinus fat invasion (SFI; n = 8). Among the pT3a group, ctDNA was detected in 75%, contrasting with only 2.8% in patients with pT1a (1/36). Detection of ctDNA was the only significant preoperative predictor of pT3a upstaging, especially in SFI. This study is the first to suggest ctDNA as a preoperative predictor of pT3a RCC upstaging from cT1a based on preoperative radiological images.

Clinical Validation of the Proenkephalin (PENK) Methylation Urine Test for Monitoring Recurrence of Non-muscle-invasive Bladder Cancer.

Background and objective: To assess the effectiveness of a urine-based proenkephalin (PENK) methylation test using linear target enrichment-quantitative methylation-specific polymerase chain reaction (mePENK test) for detection of non-muscle-invasive bladder cancer (NMIBC) recurrence compared to cytology and the NMP22 test. Methods: We first conducted a retrospective case-control study involving 54 patients with primary BC and 29 healthy individuals. We then prospectively enrolled 186 patients (January to December 2022) undergoing cystoscopy surveillance after transurethral resection of bladder tumor, of whom 59 had recurrent tumors. We analyzed voided urine samples for PENK methylation levels in urinary DNA. Cystoscopy with histology was used as the reference standard for assessing the diagnostic accuracy of the mePENK test in detecting BC recurrence. We calculated the sensitivity and specificity using receiver operating characteristic curve analysis. Survival differences were determined using the Kaplan-Meier method and Cox proportional-hazards model. A p < 0.05 was considered statistically significant. Key findings and limitations: In the case-control study, the PENK test had sensitivity of 83.3% and specificity of 100%. For NMIBC patients undergoing cystoscopy surveillance, the sensitivity was 76.3% (95% confidence interval [CI] 63.4-86.4%) and the specificity was 85% (95% CI 77.6-90.7%), outperforming cytology (sensitivity: 28.8%, 95% CI 17.8-42.1%; p < 0.001; specificity: 97.6%, 95% CI 93.2-99.5%) and the NMP22 test (sensitivity: 54.2%, 95% CI 40.7-67.2%; p = 0.016; specificity 81.9%, 95% CI 74.1-88.2%). In the high-risk group, the mePENK test had sensitivity of 89.7% (95% CI 75.8-97.1%) and a negative predictive value of 96.9%. For the group with low/intermediate risk, the sensitivity was 41.7%. In the group with negative cystoscopy, recurrence-free survival was shorter for patients with positive than for those with negative mePENK results (245 vs 503 d), with a hazard ratio of 9.4 (p < 0.001). The main study limitation is the small sample size. Conclusions and clinical implications: The mePENK test showed good performance for detection of NMIBC recurrence and has potential for use for prognosis and prediction. Patient summary: We found that a test used to analyze urine samples showed good performance in detecting recurrence of NMIBC. This noninvasive mePENK test may help in personalized follow-up care for patients with NMIBC.

Radical prostatectomy versus radiotherapy as local therapy for primary tumors in patients with oligometastatic prostate cancer.

Introduction: We compared radical prostatectomy (RP) and radiotherapy (RT) as local therapies for primary tumors and examined their associations with survival outcomes and urinary tract complications in patients with oligometastatic prostate cancer (omPC). Methods: We evaluated the data of 85 patients diagnosed with omPC who underwent local therapy for primary tumors between January 2008 and December 2018. Of the 85 patients, 31 underwent prostate RT, while 54 underwent RP. Oligometastatic disease was defined as the presence of fewer than five metastatic lesions without visceral metastasis. Urinary tract complications, progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS) were evaluated using the Kaplan-Meier method and Cox regression analyses. Results: Patients treated with RT showed higher prostate-specific antigen levels. There was no significant difference in the 5-year PFS (52.5% vs. 37.9%, p=0.351), CSS (67.6% vs. 84.7%, p=0.473), or OS (63.6% vs. 73.8%, p=0.897) between the RT and RP groups. In the multivariate analyses, the type of local therapy was not associated with PFS (hazard ratio [HR]=1.334, p=0.356), CSS (HR=0.744, p=0.475), or OS (HR=0.953, p=0.897). Conclusion: Therefore, RP seems to be a possible treatment option for patients with omPC, exhibiting oncologic outcomes comparable to those with RT.

Risks of Dementia After Treatment with an Anticholinergic, Beta-3 Agonist, or Combination of Both for an Overactive Bladder: A Korean National Cohort Study.

BACKGROUND AND OBJECTIVE: An overactive bladder (OAB) is primarily managed with behavioural therapy and using anticholinergics and beta-3 agonists. Reports have shown that the use of anticholinergics by OAB patients was associated with an increased risk of new-onset dementia compared with those using beta-3 agonists. This study compares the risks of dementia among patients with an OAB starting on a beta-3 agonist alone, an anticholinergic alone, or a combination treatment. METHODS: Using data from the Korean National Health Insurance Service database, we studied a nationwide population cohort comprising patients newly diagnosed with an OAB who initiated their OAB medications between 2015 and 2020. The treatment types were categorised as anticholinergics (oxybutynin, solifenacin, tolterodine, trospium, fesoterodine, flavoxate, and propiverine) alone, a beta-3 agonist (mirabegron) alone, and combination therapy (an anticholinergic plus the beta-3 agonist). To evaluate the impact of cumulative drug exposure, we quantified the cumulative exposure to solifenacin and mirabegron as cumulative defined daily doses (cDDDs) using proportional hazards regression analyses, adjusted for factors known to be associated with dementia. KEY FINDINGS AND LIMITATIONS: Among the study's 3 452 705 patients, 671 974 were new users of a beta-3 agonist alone (19.5%), 1 943 414 new users of anticholinergics alone (56.3%), and 837 317 receiving combination therapy (24.3%). The most common anticholinergic used both alone and as part of a combination treatment was solifenacin (42.9% and 56.3%, respectively). There was an increased risk of dementia between the users of an anticholinergic alone (adjusted hazard ratio [aHR] = 1.213; 95% confidence interval [CI], 1.195-1.232) and those taking a combination treatment (aHR = 1.345; 95% CI, 1.323-1.366) compared with the users of beta-3 agonists alone after the adjustment of covariates. However, the incidence of dementia was also significantly higher, with an increase in the cumulative dose of mirabegron (aHR = 1.062 [1.021-1.106] for 28-120 cDDDs and aHR = 1.044 [1.004-1.084)] for patients who received >121 cDDDs compared with those who received <27 cDDDs). A marked increased risk of dementia was associated with the use of solifenacin, tolterodine, fesoterodine, and propiverine, both separately and in combination with mirabegron. CONCLUSIONS AND CLINICAL IMPLICATIONS: In this large Korean cohort, the use of anticholinergics with or without a beta-3 agonist increased the risk of new-onset dementia compared with the use of a beta-3 agonist alone. Given that the risk of dementia was most significantly elevated with combination treatments, care should be taken when considering combination treatment for OAB patients with risk factors for dementia. Furthermore, there could be a possible association between beta-3 agonists and dementia, although future studies are needed. PATIENT SUMMARY: This study investigated the risk of dementia induced by overactive bladder (OAB) treatment in a large Korean cohort. Two representative OAB treatment drugs, anticholinergics and beta-3 agonists, both increased the risk of new-onset dementia. Clinicians should be cautious in using OAB treatment drugs since no drugs could be concluded as safe.

PD-1 inhibitor plus oncolytic vaccinia virus is a safe and effective treatment option for metastatic renal cell carcinoma.

BACKGROUND: Although a combination of immune checkpoint inhibitors (ICIs) is recommended as the first line treatment option for metastatic renal cell carcinoma (mRCC), several immune-related adverse events (irAEs) occur, especially hepatitis. We explored the therapeutic benefits and safety profile of combining oncolytic vaccinia virus, JX-594, with a programmed cell death protein-1 (PD-1) inhibitor. METHODS: We used early-stage and advanced-stage orthotopic murine mRCC models developed by our group. PD-1 inhibitor monotherapy or a PD-1 inhibitor combined with either JX-594 or a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor were systemically injected through the peritoneum. An immunofluorescence analysis was performed to analyze the tumor immune microenvironment (TIME). irAEs were assessed in terms of hepatitis. RESULTS: In the early-stage mRCC model mice, the combination of JX-594 and a PD-1 inhibitor significantly decreased the primary tumor size and number of lung nodules, compared with the ICI combination, but the JX-594 and PD-1 inhibitor combination and ICI combination did not differ significantly in the advanced-stage mRCC model mice. The JX-594 and PD-1 inhibitor combination induced tumor-suppressing TIME changes in both the early- and advanced-stage mRCC models. Furthermore, mice treated with the ICI combination had significantly greater hepatic injuries than those treated with the JX-594 and PD-1 inhibitor combination which was evaluated in early-stage mRCC model. CONCLUSIONS: The JX-594 and PD-1 inhibitor combination effectively reduced primary tumors and the metastatic burden, similar to ICI combination therapy, through dynamic remodeling of the TIME. Furthermore, hepatitis was significantly decreased in the JX-594 and PD-1 inhibitor combination group, suggesting the potential benefit of that combination for reducing ICI-induced toxicity.

Role of Maximal Transurethral Resection Preceding Partial Cystectomy for Muscle-Invasive Bladder Cancer.

PURPOSE: We aimed to evaluate whether maximal transurethral resection (TUR) affects the oncological outcome of partial cystectomy (PC) performed in patients with muscle-invasive bladder cancer (MIBC), although radical cystectomy (RC) and trimodal therapy (TMT) are regarded as standard treatments for MIBC. METHODS: In this retrospective study, we evaluated the data of 98 patients who underwent PC due to MIBC between January 2006 and December 2018. Of the 98 patients, 71 underwent maximal TUR. We evaluated the recurrence-free survival (PFS), pelvic recurrence-free survival (pPFS), cancer-specific survival (CSS), and overall survival (OS) using the Kaplan-Meier method according to the maximal TUR status. Variables associated with survival were analyzed using Cox regression analyses. RESULTS: The 5-year PFS (42.5% vs. 20.3%, p = 0.008), pPFS (50.7% vs. 24.1%, p = 0.003), and CSS (74.0% vs. 51.0%, p = 0.016) were also higher in patients who underwent maximal TUR. The multivariable Cox regression analysis showed that maximal TUR was associated with PFS (hazard ratio [HR] = 0.500, p = 0.029), pPFS (HR = 0.353, p = 0.004), and CSS (HR = 0.416, p = 0.027). However, maximal TUR did not affect the OS (HR = 0.618, p = 0.132). CONCLUSION: PC resulted in acceptable oncological outcomes in patients with MIBC, while maximal TUR played an important role in improving the oncological outcomes. PC after maximal TUR can be suggested as a treatment option for MIBC patients who are unable to undergo RC and TMT.

Prediction of Stent Failure for Malignant Ureteral Obstruction in Non-Urological Cancer.

PURPOSE: To analyze prognostic factors associated with ureteral stent failure and to develop a prediction model for malignant ureteral obstruction (MUO) in patients with non-urological cancers. MATERIALS AND METHODS: We retrospectively reviewed patients with non-urological cancers who underwent ureteral stenting or percutaneous nephrostomy (PCN) for MUO between 2006 and 2014. Variables predicting stent failure were identified using Cox regression analysis. RESULTS: Of the 743 patients, 468 (63.0%) underwent ureteral stenting only, and 275 (37.0%) underwent PCN owing to technical (n=215) or functional (n=60) stent failure. The median overall survival was 4 [interquartile range (IQR) 1-11] months, and the median interval duration to stent failure was 2 (IQR 0-7) months. In univariate analysis, lower gastrointestinal cancer, previous radiotherapy to the pelvis, bladder invasion, lower ureteral obstruction, and low previous estimated glomerular filtration rate (eGFR) (<30 mL/min/1.73 m²) were significantly associated with a decreased survival rate. In multivariate analysis, bladder invasion and previous eGFR were significant predictors. With these two predictors, we divided patients into three groups based on their presence: low-risk (neither factor; n=516), intermediate-risk (one factor; n=206), and high-risk (both factors; n=21). The median stent failure-free survival rates of patients in the low-, intermediate-, and high-risk groups were 26 (8-unreached), 1 (0-18), and 0 (0-0) months, respectively (p<0.001). CONCLUSION: In cases of ureteral obstruction caused by non-urological cancers, patients with bladder invasion and a low eGFR showed poor stent failure-free survival. Therefore, PCN should be considered the primary procedure for these patients.

Outcomes of single-port robotic ureteral reconstruction using the da Vinci SP® system.

PURPOSE: The da Vinci SP® robotic system enables three double-jointed wristed instruments and a fully wristed three-dimensional camera to be placed through a single port. This study presents our experience with robot-assisted ureteral reconstruction using the SP system and reports its outcomes. MATERIALS AND METHODS: Between December 2018 and April 2022, a single surgeon performed robotic ureteral reconstruction using the SP system in 39 patients: 18 underwent pyeloplasty and 21 received ureteral reimplantation. Demographic and perioperative patient data were collected and analyzed. Radiographic and symptomatic improvements were assessed 3 months after surgery. RESULTS: In pyeloplasty group, 12 patients (66.7%) were female and two patients (11.1%) had undergone previous surgery for ureteral obstruction. The median operative time was 152 minutes, the median blood loss was 8 mL, and the median length of stay in hospital was 3 days. There was one case of a complication involving postoperative percutaneous nephrostomy (PCN). In ureteral reimplantation group, 19 patients (90.5%) were female and ten patients (47.6%) had undergone gynecological surgery that caused ureteral obstruction. The median operative time was 152 minutes, the median blood loss was 10 mL, and the median length of stay in hospital was 4 days. We observed one case of open conversion and two cases of complications (colonic serosal tearing and postoperative PCN after ileal ureter replacement). The radiographic results and symptoms successfully improved following both surgeries. CONCLUSIONS: Despite adhesion-related complications, the SP system appears to be safe and effective for use in robot-assisted ureteral reconstruction.

TNM-Based Head-to-Head Comparison of Urachal Carcinoma and Urothelial Bladder Cancer: Stage-Matched Analysis of a Large Multicenter National Cohort.

PURPOSE: Outcome analysis of urachal cancer (UraC) is limited due to the scarcity of cases and different staging methods compared to urothelial bladder cancer (UroBC). We attempted to assess survival outcomes of UraC and compare to UroBC after stage-matched analyses. MATERIALS AND METHODS: Total 203 UraC patients from a multicenter database and 373 UroBC patients in single institution from 2000 to 2018 were enrolled (median follow-up, 32 months). Sheldon stage conversion to corresponding TNM staging for UraC was conducted for head-to-head comparison to UroBC. Perioperative clinical variables and pathological results were recorded. Stage-matched analyses for survival by stage were conducted. RESULTS: UraC patients were younger (mean age, 54 vs. 67 years; p < 0.001), with 163 patients (80.3%) receiving partial cystectomy and 23 patients (11.3%) radical cystectomy. UraC was more likely to harbor ≥ pT3a tumors (78.8% vs. 41.8%). While 5-year recurrence-free survival, cancer-specific survival (CSS) and overall survival were comparable between two groups (63.4%, 67%, and 62.1% in UraC and 61.5%, 75.9%, and 67.8% in UroBC, respectively), generally favorable prognosis for UraC in lower stages (pT1-2) but unfavorable outcomes in higher stages (pT4) compared to UroBC was observed, although only 5-year CSS in ≥ pT4 showed statistical significance (p=0.028). Body mass index (hazard ratio [HR], 0.929), diabetes mellitus (HR, 1.921), pathologic T category (HR, 3.846), and lymphovascular invasion (HR, 1.993) were predictors of CSS for all patients. CONCLUSION: Despite differing histology, UraC has comparable prognosis to UroBC with relatively favorable outcome in low stages but worse prognosis in higher stages. The presented system may be useful for future grading and risk stratification of UraC.

Phosphodiesterase-5 Inhibitor Use in Robot Assisted Radical Prostatectomy Patients Is Associated with Reduced Risk of Death: A Propensity Score Matched Analysis of 1,058 Patients.

PURPOSE: We investigated whether the use of a phosphodiesterase-5 inhibitor (PDE5i) after robot assited radical prostatectomy has a survival benefit over non-use patients because there are controversial results on the association between PDE5i use and survival outcomes for prostate cancer patients in literature. MATERIALS AND METHODS: We designed a retrospective, matched, large-sample cohort study of 5,545 patients who underwent robot assisted radical prostatectomy (RARP) during 2013-2021 in a single institute. The exclusion criteria was patients who were aged >70 years at surgery, American Society of Anesthesiologists (ASA) physical status classification grade 4 or 5, history of other malignancies, patients who started PDE5i 6 months after survery and patients with follow up period less than 24 months after surgery. Among the 1,843 included patients, 1,298 were PDE5i users, and 545 were PDE5i non-users. We performed propensity score matching (PSM) of PDE5i users (n=529) with non-users (n=529) by adjusting for the variables of age, Gleason grade group, pathological T stage, preoperative ASA physical status grade, and International Index of Erectile Function score. RESULTS: There were no significant difference in patient characteristics according to PSM. Kaplan-Meier curve revealed the difference of overall survival for PDE5i users and non-users (clustered log-rank test p<0.05). In a stratified Cox regression analysis, PDE5i use after RARP was associated with improved overall survival and reduced risk of death (hazard ratio 0.43; confidence interval 0.24-0.79; p=0.007). The limitation of this study was that the indication for the prescription of PDE5i was not given. CONCLUSIONS: PDE5i administration after RARP were associated with overall survival of patients with prostate cancer. A further randomized control trial may reveal whether routine use of PDE5i after prostatectomy can improve survival of prostate cancer patient.

Noninvasive studies may have potential to replace cystoscopy in non-muscle invasive bladder cancer follow-up.

Bladder cancer has a high recurrence rate which requires frequent follow-up. Cystoscopy is currently the gold standard for follow-up which is invasive and undesirable procedure for patients. We aimed to investigate the feasibility of noninvasive studies for follow-up of non-muscle invasive bladder cancer. This retrospective study was done for non-muscle invasive bladder cancer patients with abnormal lesion at follow up cystoscopy, therefore those needed transurethral resection of bladder tumor (TUR-BT). Inclusion criteria was patients who had preoperative bladder magnetic resonance imaging (MRI) within 1 month to TUR-BT and urine cytology results. MRI, urine cytology, and surgical pathology results were analyzed for sensitivity, specificity, positive and negative predictive values, accuracy, diagnostic odds ratio, and number needed to misdiagnose for the diagnostic performance of non-invasive studies. From total of 2,258 TUR-BT cases, 1,532 cases of primary TUR-BT and 481 cases which bladder MRI were not done was excluded. Finally, 245 cases of TUR-BT were included. Combined urine cytology and bladder MRI showed 96% sensitivity, 43% specificity, 89% positive and 67% negative predictive values, 87% accuracy, 16.2 diagnostic odds ratio, and 7.4 number needed to misdiagnose values. Among nine false-negative cases, three (1.2%) were missed by the radiologist, two (0.8%) had an empty bladder during magnetic resonance imaging, and three (1.2%) had gross hematuria which needed cystoscopy despite of bladder MRI or urine cytology result. Only one case (0.4%) was missed based on symptoms and noninvasive tests. However, none of the false-negative cases showed rapid extensive progression requiring radical or partial cystectomy. The combination of bladder MRI and urine cytology was comparable to cystoscopy for the follow-up of recurred lesions in non-muscle invasive bladder cancer patients for sensitivity, but not for specificity. However, it may reduce the need for cystoscopy and allowing patients to have choices for follow up diagnostic methods. Also, additional imaging tests to evaluate kidney, ureter and peri-vesical lesions can be reduced.

Characteristics of BRCA2 Mutated Prostate Cancer at Presentation.

Genetic alterations of DNA repair genes, particularly BRCA2 in patients with prostate cancer, are associated with aggressive behavior of the disease. It has reached consensus that somatic and germline tests are necessary when treating advanced prostate cancer patients. Yet, it is unclear whether the mutations are associated with any presenting clinical features. We assessed the incidences and characteristics of BRCA2 mutated cancers by targeted sequencing in 126 sets of advanced prostate cancer tissue sequencing data. At the time of diagnosis, cT3/4, N1 and M1 stages were 107 (85%), 54 (43%) and 35 (28%) samples, respectively. BRCA2 alterations of clinical significance by AMP/ASCO/CAP criteria were found in 19 of 126 samples (15.1%). The BRCA2 mutated cancer did not differ in the distributions of TNM stage, Gleason grade group or histological subtype compared to BRCA2 wild-type cancers. Yet, they had higher tumor mutation burden, and higher frequency of ATM and BRCA1 mutations (44% vs. 10%, p = 0.002 and 21% vs. 4%, p = 0.018, respectively). Of the metastatic subgroup (M1, n = 34), mean PSA was significantly lower in BRCA2 mutated cancers than wild-type (p = 0.018). In the non-metastatic subgroup (M0, n = 64), PSA was not significantly different (p = 0.425). A similar trend was noted in multiple metastatic prostate cancer public datasets. We conclude that BRCA2 mutated metastatic prostate cancers may present in an advanced stage with relatively low PSA.

Nephron-Sparing Approaches in Upper Tract Urothelial Carcinoma: Current and Future Strategies.

Upper tract urothelial carcinoma (UTUC) is a relatively rare cancer, and much of the approach to treatment has been derived from strategies employed in treating bladder cancer. Radical nephroureterectomy (RNU) is regarded as the gold standard treatment for UTUC. However, due to potential complications, such as renal function impairment, that can affect oncologic outcomes, the demand for nephron-sparing treatment to effectively treat cancer while preserving renal function has increased. As a result, various treatment methods for low-grade, low-volume UTUC, such as segmental ureterectomy, endoscopic resection, and intraluminal therapy, have been attempted and reported. Although these treatment modalities have exhibited acceptable oncological results, further studies are required. In the future, the introduction of new technologies, such as improved diagnostic and surgical equipment, and new drug delivery systems, could enhance the effectiveness of nephron-sparing strategies in the treatment of UTUC. Additionally, understanding the biological and genetic characteristics of UTUC that distinguish it from those of bladder cancer will also aid in establishing strategies for nephron-sparing.

Clinical Implications for da Vinci SP Partial Nephrectomy in High-Complexity Tumors: Propensity Score-Matching Analysis.

Purpose: To compare surgical outcomes between robot-assisted laparoendoscopic single-site (R-LESS) surgery using the da Vinci Si or Xi system and the da Vinci SP system for partial nephrectomy. Materials and Methods: From 2008 to 2020, 66 partial nephrectomies were performed using a single-site robotic approach: 44 used the da Vinci Xi or Si system (R-LESS group) and 22 used the da Vinci SP system (SP group). After 1:1 propensity score matching, surgical outcomes were compared between groups. Results: Median patient age was 51.5 years. Median tumor size was 2.1 cm and was not significantly different between groups. Median operation time was longer in the R-LESS group (R-LESS vs SP: 180 vs 155 minutes, p = 0.034), but median warm ischemic time was comparable between groups. Estimated blood loss was higher in the R-LESS group (R-LESS vs SP: 215 vs 20 mL, p < 0.001). Median operation time was significantly shorter in the SP group in patients with moderate- to high-complexity tumors (R-LESS vs SP: 200 vs 172 minutes, p = 0.035). Rates of trifecta achievement were similar between groups (63.6% in both groups, p = 1.00). Conclusions: R-LESS and da Vinci SP methods are both feasible approaches for single-site incision robotic partial nephrectomy. The da Vinci SP platform allows "true" single-site surgery without additional ports and provides a wider working space. It was associated with better performance than R-LESS partial nephrectomy. In complex tumors, operation time was shorter with SP partial nephrectomy than with R-LESS partial nephrectomy, suggesting that the SP method is especially advantageous for managing complex renal tumors.

Gene Expression Analysis of Aggressive Adult Xp11.2 Translocation Renal Cell Carcinoma at Clinical Stage T1N0M0 to Identify Potential Prognostic and Therapeutic Biomarkers.

Xp11.2 translocation renal cell carcinoma (tRCC), involving transcription factor E3 (TFE3) gene fusions, is a rare and aggressive RCC variant when present in adults and has been recently recognized as a unique entity in RCC. Biomarkers and treatment guidelines do not exist for patients with aggressive Xp11.2 tRCC. The aim was to identify and evaluate therapeutic biomarkers for aggressive Xp11.2 tRCC. RNA sequencing was performed using formalin-fixed, paraffin-embedded tissues from 11 adult patients with clinical T1N0M0 Xp11.2 tRCC, including three patients with aggressive characteristics (recurrence or cancer-specific death after nephrectomy). Thirty genes were differentially expressed between the aggressive and non-aggressive groups, even after adjustment, and were associated with KEGG pathways related to the aggressiveness of Xp11.2 tRCC. PIK3R2, involved in various KEGG pathways, including the PI3K/AKT/mTOR pathway, was overexpressed in the Xp11.2 tRCC cell lines UOK120 and UOK146. The PI3K pathway inhibitor LY294002 showed a significant therapeutic benefit. This study provides the first candidate biomarker, PIK3R2, for aggressive clinical T1N0M0 Xp11.2 tRCC. Furthermore, this study is the first to recommend a targeted drug, LY294002, for aggressive Xp11.2 tRCC based on the molecular pathophysiology.

Systemic Injection of Oncolytic Vaccinia Virus Suppresses Primary Tumor Growth and Lung Metastasis in Metastatic Renal Cell Carcinoma by Remodeling Tumor Microenvironment.

Immune checkpoint inhibitors and tyrosine kinase inhibitors are the first-line treatment for metastatic renal cell carcinoma (mRCC), but their benefits are limited to specific patient subsets. Here, we aimed to evaluate the therapeutic efficacy of JX-594 (pexastimogene devacirepvec, Pexa-vec) monotherapy by systemic injection in comparison with sunitinib monotherapy in metastatic orthotopic RCC murine models. Two highly metastatic orthotopic RCC models were developed to compare the treatment efficacy in the International Metastatic RCC Database Consortium favorable-risk and intermediate- or poor-risk groups. JX-594 was systemically injected through the peritoneum, whereas sunitinib was orally administered. Post-treatment, tumor microenvironment (TME) remodeling was determined using immunofluorescence analysis. Systemic JX-594 monotherapy injection demonstrated therapeutic benefit in both early- and advanced-stage mRCC models. Sunitinib monotherapy significantly reduced the primary tumor burden and number of lung metastases in the early-stage, but not in the advanced-stage mRCC model. Systemic JX-594 delivery remodeled the primary TME and lung metastatic sites by increasing tumor-infiltrating CD4/8+ T cells and dendritic cells. Systemic JX-594 monotherapy demonstrated significantly better therapeutic outcomes compared with sunitinib monotherapy in both early- and advanced-stage mRCCs by converting cold tumors into hot tumors. Sunitinib monotherapy effectively suppressed primary tumor growth and lung metastasis in early-stage mRCC.

Evaluation of the Surgical Margin Threshold for Avoiding Recurrence after Partial Nephrectomy in Patients with Renal Cell Carcinoma.

PURPOSE: An adequate minimal surgical margin for partial nephrectomy (PN) has not yet been conclusively established. Therefore, we aimed to compare PN recurrence rates according to surgical margin status and to establish an adequate minimal surgical margin. MATERIALS AND METHODS: We retrospectively studied patients with clinically localized renal cell carcinoma who underwent PN between 2005 and 2014. Surgical margin width (SMW) was assessed for all surgical tissues and divided into three groups: SMW <1 mm, SMW ≥1 mm, and positive surgical margin (PSM). The data were analyzed using the Kaplan-Meier method with log-rank tests and multivariate Cox regression models. RESULTS: Of 748 patients (median age, 55 years; interquartile range, 46-64 years; 220 female), 704 (94.2%) and 44 (5.8%) patients had negative and PSMs, respectively. Recurrence-free survival was significantly lower in patients with PSMs (p<0.001) and was not significantly different between SMW ≥1 mm and <1 mm groups (p=0.604). PSM was a significant predictor of recurrence (hazard ratio: 8.03, 95% confidence interval: 2.74-23.56, p<0.001), in contrast to SMW <1 mm (p=0.680). CONCLUSION: A PSM after PN significantly increases the risk of recurrence. We discovered that even a submillimeter safety surgical margin may be enough to prevent recurrence. To maximize normal renal parenchyma preservation and to avoid cancer recurrence in renal parenchymal tumor patients, PN may be a safe treatment, except for those with a PSM in the final pathology.

Effect of Dexmedetomidine on Biochemical Recurrence in Patients after Robot-Assisted Laparoscopic Radical Prostatectomy: A Retrospective Study.

The usage of dexmedetomidine during cancer surgery in current clinical practice is debatable, largely owing to the differing reports of its efficacy based on cancer type. This study aimed to investigate the effects of dexmedetomidine on biochemical recurrence (BCR) and radiographic progression in patients with prostate cancer, who have undergone robot-assisted laparoscopic radical prostatectomy (RALP). Using follow-up data from two prospective randomized controlled studies, BCR and radiographic progression were compared between individuals who received dexmedetomidine (n = 58) and those who received saline (n = 56). Patients with complete follow-up records between July 2013 and June 2019 were enrolled in this study. There were no significant between-group differences in the number of patients who developed BCR and those who showed positive radiographic progression. Based on the Cox regression analysis, age (p = 0.015), Gleason score ≥ 8 (p < 0.001), and pathological tumor stage 3a and 3b (both p < 0.001) were shown to be significant predictors of post-RALP BCR. However, there was no impact on the dexmedetomidine or control groups. Low-dose administration of dexmedetomidine at a rate of 0.3-0.4 µg/kg/h did not significantly affect BCR incidence following RALP. In addition, no beneficial effect was noted on radiographic progression.