Age Does Not Impact Cancer Specific Mortality: From Sub-Distributional and Cause-Specific Hazard Analysis in RCC Patients Undergoing Radical Nephrectomy and Thrombectomy.

OBJECTIVE: To assess the impact of age on cancer-specific mortality (CSM) and other-cause mortality (OCM) in patients undergoing radical nephrectomy with thrombectomy (RNTx) for renal cell carcinoma (RCC) with venous thrombus. PATIENTS AND METHODS: We retrospectively analyzed 196 patients who underwent RNTx for RCC with venous thrombus between 1990 and 2018 at a single tertiary referral center. Patients were categorized into three age groups: <60, 60-69, and ≥70 years. The cumulative incidence function (CIF) for CSM and OCM was calculated using the Aalen-Johansen estimator, and hazard ratios (HR) from sub-distributional hazard (SDH) and cause-specific hazard (CSH) models were employed to assess the impact of age on mortality. RESULTS: The median follow-up was 40.5 months. Of the 196 patients, 105 experienced disease progression, 125 had cancerrelated deaths, and 155 died from any cause. Perioperative outcomes, including ICU admission, 90-day readmission, and 90-day mortality, were similar across age groups. The CIF for 5-year CSM differed significantly among age groups (p = 0.032), though this difference was not observed at 10 years. OCM increased significantly with age, particularly in the ≥70 group at 10 years (p = 0.045). Multivariable SDH and CSH models showed no significant differences in CSM between age groups. CONCLUSION: While age was associated with increased OCM, it did not significantly impact the hazard of CSM. Older age alone should not be considered a contraindication for surgical intervention in RCC with venous thrombus.

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.

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.

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.

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.

Invasiveness of Upper Tract Urothelial Carcinoma: Clinical Significance and Integrative Diagnostic Strategy.

PURPOSE: In this study, we aimed to determine the clinicopathologic, radiologic, and molecular significance of the tumor invasiveness to further stratify the patients with high-grade (HG) upper tract urothelial carcinoma (UTUC) who can be treated less aggressively. MATERIALS AND METHODS: Clinicopathologic and radiologic characteristics of 166 surgically resected HG UTUC (48 noninvasive, and 118 invasive) cases were evaluated. Six noninvasive UTUC cases with intratumoral tumor grade heterogeneity were selected for whole-exome sequencing (WES) to understand the underlying molecular pathophysiology. Barcode-tagging sequencing was done for validation of the target genes from WES data. RESULTS: Patients with noninvasive UTUC showed no cancer-specific death with better cancer-specific survival (p < 0.001) and recurrence-free survival (p < 0.001) compared to the patients with invasive UTUC. Compared to the invasive UTUC, noninvasive UTUC was correlated to a low grade (LG) on the preoperative abdominal computed tomography (CT) grading system (p < 0.001), histologic intratumoral tumor grade heterogeneity (p=0.018), discrepancy in preoperative urine cytology diagnosis (p=0.018), and absence of urothelial carcinoma in situ (p < 0.001). WES of the heterogeneous components showed mutually shared HRAS and FGFR3 mutations shared between the HG and LG components. HRAS mutation was associated with the lower grade on preoperative abdominal CT and intratumoral tumor grade heterogeneity (p=0.045 and p < 0.001, respectively), whereas FGFR3 mutation was correlated to the absence of carcinoma in situ (p < 0.001). CONCLUSION: According to our comprehensive analysis, HG noninvasive UTUC can be preoperatively suspected based on distinct preoperative radiologic, cytologic, histologic, and molecular features. Noninvasive HG UTUC shows excellent prognosis and thus should be treated less aggressively.

Glutathione dynamics is a potential predictive and therapeutic trait for neoadjuvant chemotherapy response in bladder cancer.

Radical cystectomy with preoperative cisplatin-based neoadjuvant chemotherapy (NAC) is the standard care for muscle-invasive bladder cancers (MIBCs). However, the complete response rate to this modality remains relatively low, and current clinicopathologic and molecular classifications are inadequate to predict NAC response in patients with MIBC. Here, we demonstrate that dysregulation of the glutathione (GSH) pathway is fundamental for MIBC NAC resistance. Comprehensive analysis of the multicohort transcriptomes reveals that GSH metabolism and immune-response genes are enriched in NAC-resistant and NAC-sensitive MIBCs, respectively. A machine-learning-based tumor/stroma classifier is applied for high-throughput digitalized immunohistochemistry analysis, finding that GSH dynamics proteins, including glutaminase-1, are associated with NAC resistance. GSH dynamics is activated in cisplatin-resistant MIBC cells, and combination treatment with a GSH dynamics modulator and cisplatin significantly suppresses tumor growth in an orthotopic xenograft animal model. Collectively, these findings demonstrate the predictive and therapeutic values of GSH dynamics in determining the NAC response in MIBCs.

Kidney sparing surgery in upper tract urothelial carcinoma: paradigm change in surgical treatment for ureter cancer.

PURPOSE: To extend the indications of kidney-sparing surgery (KSS) for ureter cancer by comparing the oncological outcomes between patients with upper tract urothelial carcinoma (UTUC) who underwent radical nephroureterectomy (RNU) or KSS. METHODS: We retrospectively reviewed 708 patients with UTUC who underwent RNU (N = 646) or KSS (N = 62) between 2011 and 2019 to analyze the oncologic outcomes and prognostic factors. Subgroup analyses were performed for patients with unifocal ureteral urothelial carcinoma (UC). RESULTS: No significant difference was observed in the overall survival (OS) or cancer-specific survival (CSS) between RNU and KSS (distal ureterectomy with reimplantation (N = 33), ureterectomy with ileal ureter (N = 14), ureteroscopic tumor resection (N = 10), and ureterectomy with ureteroureterostomy (N = 5)). Among 269 (38.0%) patients with unifocal ureteral UC, 219 and 50 patients underwent RNU and KSS, respectively. OS and CSS were not significantly different between these two groups. Pathologic stage was a significant risk factor in multivariate analysis (hazard ratio = 2.621; p = 0.000). Among 646 RNU patients, 219 (33.9%) had unifocal ureteral UC, 40 (18.3%) with low-grade tumors. Among these, 13 (5.9%) patients with unifocal, low-grade and small (< 2 cm) tumors received nephroureterectomy. CONCLUSION: Kidney-sparing surgery should be regarded as an important alternative to RNU for patients with unifocal ureteral UC thought to have noninvasive disease to preserve renal function and reduce overtreatment.

Effect of decreased renal function on poor oncological outcome after radical cystectomy.

PURPOSE: To evaluate the impact of preoperative renal impairment on the oncological outcomes of patients with urothelial carcinoma who underwent radical cystectomy. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients with urothelial carcinoma who underwent radical cystectomy from 2004 to 2017. All patients who underwent preoperative 99mTc-diethylenetriaminepentaacetic acid renal scintigraphy (DTPA) were identified. We divided the patients into two groups according to their glomerular filtration rates (GFRs): GFR group 1, GFR≥90 mL/min/1.73 m²; GFR group 2, 60≤GFR<90 mL/min/1.73 m². We included 89 patients in GFR group 1 and 246 patients in GFR group 2 and compared the clinicopathological characteristics and oncological outcomes between the two groups. RESULTS: The mean time required for recurrence was 125.5±8.0 months in GFR group 1 and 85.7±7.4 months in GFR group 2 (p=0.030). The mean cancer-specific survival was 131.7±7.8 months in GFR group 1 and 95.5±6.9 months in GFR group 2 (p=0.051). The mean overall survival was 123.3±8.1 months in GFR group 1 and 79.5±6.6 months in GFR group 2 (p=0.004). CONCLUSIONS: Preoperative GFR values in the range of 60≤GFR<90 mL/min/1.73 m² are independent prognostic factors for poor recurrence-free survival, cancer-specific survival, and overall survival in patients after radical cystectomy compared with GFR values of ≥90 mL/min/1.73 m².

Efficacy and Safety of Human Bone Marrow-Derived Mesenchymal Stem Cells according to Injection Route and Dose in a Chronic Kidney Disease Rat Model.

Background and Objectives: We compared the efficacy and safety of human bone marrow-derived mesenchymal stem cells (hBMSC), delivered at different doses and via different injection routes in an animal model of chronic kidney disease. Methods and Results: A total of ninety 12-week-old rats underwent 5/6 nephrectomy and randomized among nine groups: sham, renal artery control (RA-C), tail vein control (TV-C), renal artery low dose (RA-LD) (0.5×106 cells), renal artery moderate dose (RA-MD) (1.0×106 cells), renal artery high dose (RA-HD) (2.0×106 cells), tail vein low dose (TV-LD) (0.5×106 cells), tail vein moderate dose (TV-MD) (1.0×106 cells), and tail vein high dose (TV-HD) (2.0×106 cells). Renal function and mortality of rats were evaluated after hBMSC injection. Serum blood urea nitrogen was significantly lower in the TV-HD group at 2 weeks (p<0.01), 16 weeks (p<0.05), and 24 weeks (p<0.01) than in the TV-C group, as determined by one-way ANOVA. Serum creatinine was significantly lower in the TV-HD group at 24 weeks (p<0.05). At 8 weeks, creatinine clearance was significantly higher in the TV-MD and TV-HD groups (p<0.01, p<0.05) than in the TV-C group. In the safety evaluation, we observed no significant difference among the groups. Conclusions: Our findings confirm the efficacy and safety of high dose (2×106 cells) injection of hBMSC via the tail vein.

No difference in follow-up estimated glomerular filtration rate between hypertensive and matched nonhypertensive kidney donors.

BACKGROUND: According to current guidelines, kidney donor candidates with controlled hypertension using 1 or 2 antihypertensive drugs may be considered as donor. However, this recommendation is based on the study that antihypertensive drug was initiated in mainly "after donor registration" and this may be white-coat hypertension because of donation-related anxiety. We compared the follow-up eGFR between kidney donors with preexisting hypertension and matched nonhypertensive donors. METHODS: This single-center retrospective study classified 97 living hypertensive donors previously receiving antihypertensive drugs into two groups: 1 drug group (61 donors) and 2 drugs group (36 donors). We compared the follow-up eGFR between each donor previously receiving antihypertensive drugs and three matched nonhypertensive donors in terms of age, sex, and follow-up duration. RESULTS: At a mean (range) of 51 months (12-214) in the 1 drug group, and 54 months (12-175) in the 2 drugs group after donation, there was no significant difference in follow-up eGFR between hypertensive donors previously receiving antihypertensive drugs and matched controls in each group and in total donors. There was no difference in the incidence of the patients with follow-up eGFR<45mL/min/m2 in each group and their matched controls. Multiple linear regression analysis showed that baseline eGFR was the only independent predictor for the final follow-up eGFR in the total donors. CONCLUSION: Our results support the current guidelines that donor candidates with controlled hypertension using 1 or 2 antihypertensive drugs may be considered as donors, and may increase the strength of this recommendation.

Clinical Implication of Preoperative Renal Function on Oncological Outcomes in Patients with Upper Tract Urothelial Carcinoma after Radical Nephroureterectomy.

This study aims to evaluate the impact of preoperative renal function on oncological outcomes in patients with upper tract urothelial carcinoma (UTUC) who underwent radical nephroureterectomy (RNU). We performed a retrospective analysis of patients who underwent RNU between 2000 and 2012 at six academic centers. The patients were stratified into two groups based on preoperative renal function: eGFR < 60 mL/min/1.73 m2 (chronic kidney disease; CKD) and eGFR ≥ 60 mL/min/1.73 m2 (non-CKD). We investigated oncological outcomes, including overall survival, cancer-specific survival, and progression-free survival dichotomized by preoperative renal function. Multivariable Cox proportional hazards regression was used to determine if preoperative CKD was associated with oncological outcomes. In total, 1733 patients were eligible for the present study (CKD = 707 and non-CKD = 1026). Significant differences were noted in the clinical and pathologic features among the two groups, including age, sex, tumor localization, pathological T stage, tumor grade, and number of patients who received adjuvant chemotherapy. The estimated five-year overall survival (79.4 vs. 67.5%, log-rank p < 0.001), cancer-specific survival (83.5 vs. 73.6%, log-rank p < 0.001), and progression-free survival (74.6 vs. 61.5%, log-rank p < 0.001) were significantly different between the two groups, longer in the non-CKD group. Upon multivariable analysis, preoperative CKD status was associated with increased risk of overall mortality, cancer-specific mortality, and progression (p = 0.010, p = 0.016, and p = 0.008, respectively). UTUC patients with preoperative CKD had a higher risk of poor overall survival, cancer-specific survival, and progression-free survival after RNU than those without CKD.

The CDK1/TFCP2L1/ID2 cascade offers a novel combination therapy strategy in a preclinical model of bladder cancer.

Aberrant activation of embryogenesis-related molecular programs in urothelial bladder cancer (BC) is associated with stemness features related to oncogenic dedifferentiation and tumor metastasis. Recently, we reported that overexpression of transcription factor CP2-like protein-1 (TFCP2L1) and its phosphorylation at Thr177 by cyclin-dependent kinase-1 (CDK1) play key roles in regulating bladder carcinogenesis. However, the clinical relevance and therapeutic potential of this novel CDK1-TFCP2L1 molecular network remain elusive. Here, we demonstrated that inhibitor of DNA binding-2 (ID2) functions as a crucial mediator by acting as a direct repressive target of TFCP2L1 to modulate the stemness features and survival of BC cells. Low ID2 and high CDK1 expression were significantly associated with unfavorable clinical characteristics. TFCP2L1 downregulated ID2 by directly binding to its promoter region. Consistent with these findings, ectopic expression of ID2 or treatment with apigenin, a chemical activator of ID2, triggered apoptosis and impaired the proliferation, suppressed the stemness features, and reduced the invasive capacity of BC cells. Combination treatment with the specific CDK1 inhibitor RO-3306 and apigenin significantly suppressed tumor growth in an orthotopic BC xenograft animal model. This study demonstrates the biological role and clinical utility of ID2 as a direct target of the CDK1-TFCP2L1 pathway for modulating the stemness features of BC cells.

Solo-surgeon pure laparoscopic donor nephrectomy using passive camera holder: IDEAL stage 2a study.

BACKGROUND: Solo-surgery can be defined as a practice of a surgeon operating alone using a camera holder, without other surgical members except for a scrub nurse. This study was designed to evaluate the feasibility and safety of solo-surgeon pure laparoscopic donor nephrectomy. METHODS: The study protocol was approved by the Institutional Review Board of Asan Medical Center, Seoul, Korea. The brief study protocol was registered on the Clinical Research Information Service site of the Korea Centers for Disease Control and Prevention. Candidates fulfilling all inclusion and exclusion criteria were enrolled in the clinical trial and underwent solo-surgeon pure laparoscopic donor nephrectomy. The feasibility was assessed by the proportion of subjects who could undergo solo-surgeon pure laparoscopic donor nephrectomy without difficulty. The perioperative complications were identified to assess the safety of solo-surgeon pure laparoscopic donor nephrectomy. RESULTS: Of the 47 potential candidates from November 2018 to August 2019, 40 were enrolled in the clinical trial and seven excluded due to declining participation. The feasibility of solo-surgeon pure laparoscopic donor nephrectomy was 100%, without an occasion of any difficulty requiring conversion to the human assisted pure laparoscopic donor nephrectomy. Fourteen intraoperative complications occurred in 10 patients. The most common intraoperative complication was spleen injury. Two of three cases classified as the Satava classification grade II were due to the incomplete stapling of endoscopic stapler. Seventy-eight postoperative complications occurred in 34 patients. The most common postoperative complication was nausea/vomiting and followed by aspartate aminotransferase/alanine aminotransferase elevation. Most postoperative complication was independent of the solo-surgery itself. CONCLUSIONS: Solo-surgeon pure laparoscopic donor nephrectomy using passive camera holder is technically feasible. In terms of safety, it is necessary to adjust the scope of surgery performed alone. Trial Registration CRIS, KCT0003458. Registered 30/01/2019, Retrospectively registered, https://cris.nih.go.kr/cris/search/detailSearch.do/15868 .

Clinical features and oncological outcomes of primary female urethral cancer.

PURPOSE: Investigation of the clinical features and treatment outcomes of primary female urethral cancer (FUC) at a single institution. MATERIALS AND METHODS: We retrospectively reviewed 32 FUC patients during 1997-2017. We investigated preoperative risk factors predicting overall (overall survival [OS]) and recurrence-free survival (RFS) and reviewed clinical features, treatment modality, and oncologic outcomes according to pathology. The median follow-up duration and age was 56 months (range: 4-229) and 61 years (range: 15-82), respectively. RESULTS: The median OS and RFS were 70 and 16 months, respectively. A total of 19 (59.4%) patients received systemic chemotherapy, including 14 (43.8%) who received radiation therapy. Further, 22 patients (68.8%) underwent surgery. On univariate analysis, >T2, N+, and tumor size ≥3 cm were associated with poorer OS. There were 15 cases of distant metastasis and five local recurrences. Outcomes were poorest in adenocarcinoma (AC), moderate in clear cell carcinoma and transitional cell carcinoma, and best in squamous cell carcinoma (SCC). CONCLUSION: Female urethral lesions should be carefully examined to exclude FUC. Distal urethral SCC was responsive to surgical excision, but proximal urethral AC had poor oncological outcome even after extensive treatment. Due to the heterogeneity and poor prognosis of FUC, multimodal treatment is mandatory.

The Prognosis and the Role of Adjuvant Chemotherapy for Node-Positive Bladder Cancer Treated with Neoadjuvant Chemotherapy Followed by Surgery.

PURPOSE: This study aims to evaluate the prognosis of pathologically node-positive bladder cancer after neoadjuvant chemotherapy, the role of adjuvant chemotherapy in these patients, and the value of preoperative clinical evaluation for lymph node metastases. MATERIALS AND METHODS: Patients who received neoadjuvant chemotherapy followed by partial/radical cystectomy and had pathologically confirmed lymph node metastases between January 2007 and December 2019 were identified and analyzed. RESULTS: A total of 53 patients were included in the study. The median age was 61 years (range, 34 to 81 years) with males comprising 86.8%. Among the 52 patients with post-neoadjuvant/pre-operative computed tomography results, only 33 patients (63.5%) were considered positive for lymph node metastasis. Sixteen patients (30.2%) received adjuvant chemotherapy (AC group), and 37 patients did not (no AC group). With the median follow-up duration of 67.7 months, the median recurrence-free survival (RFS) and the median overall survival (OS) was 8.5 months and 16.2 months, respectively. The 2-year RFS and OS rates were 23.3% and 34.6%, respectively. RFS and OS did not differ between the AC group and no AC group (median RFS, 8.8 months vs. 6.8 months, p=0.772; median OS, 16.1 months vs. 16.3 months, p=0.479). Thirty-eight patients (71.7%) experienced recurrence. Distant metastases were the dominant pattern of failure in both the AC group (91.7%) and no AC group (76.9%). CONCLUSION: Patients with lymph node-positive disease after neoadjuvant chemotherapy followed by surgery showed high recurrence rates with limited survival outcomes. Little benefit was observed with the addition of adjuvant chemotherapy.

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.

Impact of preoperative chemotherapy on pathologic nodal status in muscle-invasive bladder cancer: optimal lymphadenectomy in the preoperative chemotherapy era.

PURPOSE: To investigate the impact of preoperative chemotherapy (pCTX) on pathologic nodal (pN) status and evaluate the optimal lymphadenectomy method according to clinical nodal (cN) status in patients with muscle-invasive bladder cancer who received pCTX. MATERIALS AND METHODS: We retrospectively reviewed 449 patients with muscle-invasive bladder cancer who underwent radical cystectomy. Among them, 139 (31.0%) received pCTX. We analyzed overall survival among three groups (cN-pCTX-, cN-pCTX+, and cN+pCTX+); the impact of lymphadenectomy extent according to the history of pCTX in cN- patients (n = 393); and the pN status which includes number of positive lymph nodes, and lymph node density in cN- patients who underwent extended lymphadenectomy (n = 222). RESULTS: Overall survival was significantly dependent on cN status, and pCTX had no survival advantage although it decreased the percentage of pN+ patients and the number of positive lymph nodes in cN- patients. Lymph node density showed a significant prognostic effect on overall survival in Cox regression analysis both in cN- and cN+ patients. In cN- patients, there was no significant survival difference according to lymphadenectomy extent regardless of receiving pCTX. CONCLUSIONS: pCTX can control micrometastases but not overt metastases, despite decreasing the number of positive lymph nodes in patients with muscle-invasive bladder cancer. Although extended lymphadenectomy is a reasonable diagnostic strategy in the pCTX era, standard dissection is as therapeutic as extended dissection in patients with cN- disease.

A retrospective multicenter comparison of conditional cancer-specific survival between laparoscopic and open radical nephroureterectomy in locally advanced upper tract urothelial carcinoma.

BACKGROUND: Upper urinary tract urothelial carcinomas are relatively rare and have a cancer-specific survival rate of 20%-30%. The current gold standard treatment for nonmetastatic high-grade urinary tract urothelial carcinoma is radical nephroureterectomy with bladder cuff resection. OBJECTIVE: This study aimed to compare conditional cancer-specific survival between open radical nephroureterectomy and laparoscopic radical nephroureterectomy in patients with nonmetastatic stage pT3-4 or TxN(+) locally advanced urinary tract urothelial carcinoma from five tertiary centers. METHODS: The medical records of 723 patients were retrospectively reviewed. The patients had locally advanced and nodal staged tumors and had undergone open radical nephroureterectomy (n = 388) or laparoscopic radical nephroureterectomy (n = 260) at five tertiary Korean institutions from January 2000 and December 2012. To control for heterogenic baseline differences between the two modalities, propensity score matching and subgroup analysis were conducted. Conditional survival analysis was also conducted to determine survival outcome and to overcome differences in follow-up duration between the groups. RESULTS: During the median 50.8-month follow up, 255 deaths occurred. In univariate analysis, significant factors affecting cancer-specific survival (e.g., age, history of bladder cancer, American Society of Anesthesiologists score, pathological N stage, and presence of lymphovascular invasion and carcinoma in situ) differed in each subsequent year. The cancer-specific survival between patients treated with open radical nephroureterectomy and laparoscopic radical nephroureterectomy was not different between patients with and without a history of bladder cancer. After adjusting baseline differences between the two groups by using propensity score matching, both groups still had no significant differences in cancer-specific survival. CONCLUSION: The two surgical modalities showed no significant differences in the 5-year cancer-specific survival in patients with locally advanced urinary tract urothelial carcinoma.

Technical Notes on Fluoroscopy-Guided Removal of Metallic Ureteral Stents.

This report describes various techniques for fluoroscopy-guided removal of metallic ureteral stents. Fifteen patients underwent 17 fluoroscopy-guided removal procedures of 22 metallic ureteral stents. The simple or modified snare or retrieval hook technique was primarily used for antegrade access, whereas the loop snare technique was primarily used for retrograde access. Overall, 64.7% of the stents were removed using the initial retrieval technique, and 82.4% of the stents were removed using an adjunct technique. Procedure-related complications included hematuria in 41.2% of cases and resolved spontaneously in all patients. Fluoroscopy-guided removal of metallic ureteral stents is safe and effective.