Clinical, Prognosis, and Treatment Effect Features Analysis of Metachronous and Synchronous UTUC and BUC.

OBJECTIVE: To provide a comprehensive understanding of the clinical features of patients with synchronous and metachronous upper tract urothelial carcinoma (UTUC) and bladder urothelial carcinoma (BUC) and inform surgical and postoperative adjuvant treatment planning. PATIENTS AND METHOD: A total of 292 consecutive patients with synchronous and metachronous UTUC-BUC were retrospectively enrolled and were categorized into three groups: (1) UTUC metachronous BUC (N = 185, UTUC-mBUC), (2) BUC-metachronous UTUC (N = 43, BUC-mUTUC), (3) synchronous UTUC-BUC (N = 64, sUTUC-BUC). We compared pathological characteristics and survival data among groups with Wilcoxon's rank sum tests, Pearson's chi-squared, and the Kaplan-Meier method. RESULTS: In the sUTUC-BUC group, a higher proportion of patients exhibited UTUC tumors with grade G3 (56%, P = .001) and stage T4 (6%, P < .001) than group UTUC-mBUC (G3 = 16%, T4 = 0%). The proportion of patients with variant histology subtype in group sUTUC-BUC was higher than that of metachronous UTUC-BUC, involving squamous (P = .003), adenoid (P = .012), and sarcomatoid (P < .001) differentiation. It was also observed that the maximum diameter of the UTUC tumor of group sUTUC-BUC (median = 3.5) was significantly larger than group UTUC-mBUC (median = 2.5, P = .002) and group BUC-mUTUC (median = 2.2, P < .001). Notably, sUTUC-BUC has an increased risk of cancer-specific death compared with UTUC-mBUC (P < .001) and BUC-mUTUC (P < .001). On multivariable Cox regression, synchronous UTUC-BUC was an independent predictor of both RFS (P < .001; vs. UTUC-mBUC: HR 0.555, P = .004; vs. BUC-mUTUC: HR 0.279, P < .001) and CSS (P < .001, HR 29.737). Moreover, sUTUC-BUC showed a better response to intravesical therapy and chemotherapy with higher cancer-specific survival (P < .001) and recurrence-free survival (P = .034). CONCLUSIONS: The prognosis and pathological characteristics among different metachronous and synchronous UTUC and BUC were diverse. The synchronous UTUC-BUC group showed variant histology subtype, high-grade tumors, advanced tumors, multifocal UTUC, worse cancer-specific survival, but better response to intravesical therapy and chemotherapy.

Conventional ultrasonography enabled with augmented reality needle guidance for percutaneous kidney access: An innovative methodologies randomized controlled trial.

IMPORTANCE: Successful needle puncture of the renal collecting system is a critical but difficult procedure in percutaneous nephrolithotomy (PCNL). Although fluoroscopy and ultrasound are the standard imaging techniques to guide puncture during PCNL, both have known limitations. OBJECTIVE: To assess the feasibility and safety of a new navigation system for needle puncture in ultrasound-guided PCNL. DESIGN: This study employed a single-center randomized controlled trial (RCT) design to assess the feasibility and safety of a new navigation system for needle puncture in ultrasound-guided PCNL. Conducted between May 2021 and November 2021, the trial utilized computer-generated random numbers for participant allocation to control for selection bias. SETTING: The trial was executed at the *********, which serves as an academic medical center. PARTICIPANTS: All patients who met the inclusion criteria were randomly divided into two groups, with 29 patients in each group. One group underwent PCNL procedures using the new navigation system, while the control group underwent standard ultrasound-guided PCNL procedures. Included patients had renal pelvis or caliceal calculi larger than 2.0 cm in diameter or had multiple or staghorn stones. The puncture procedure was performed with the support of real-time ultrasound imaging and visual guidance displayed on the screen. MAIN OUTCOMES AND MEASURES: The primary outcome was system feasibility and puncture success rate. Secondary outcomes included puncture time, total surgical time, number of attempts, post-procedure complications, and one-year and three-year stone recurrence rates. Stone clearance was defined by postoperative CT. Descriptive statistics summarized patient demographics, stone size, and location. Independent samples t-tests analyzed puncture time and total surgical time. Chi-square or Fisher's exact tests compared stone clearance, complications, socioeconomic status, renal hydronephrosis, stone location, race, and medical history. Linear regression examined the correlation between BMI and puncture time. Significance was set at P<0.05. RESULTS: For all 58 patients undergoing PCNL, needle punctures of the renal collecting system were completed with a success rate of 100%. The average time from planning the puncture protocol to successful puncture was significantly shorter in the AcuSee guidance system group (3.12 min, range 0.2-6.88 min) compared to the standard ultrasound-guided group (7.58 min, range 5.41-10.68 min), representing a reduction of approximately 59%. The total surgical time was also shorter in the AcuSee group for patients with no and mild hydronephrosis (P<0.05). Complication rates were lower in the AcuSee group, with no major complications observed. However, 3 patients in the standard ultrasound-guided group have adverse effects after the PCNL procedure. The one-year stone recurrence rate was significantly lower in the AcuSee group (3.4%) compared to the standard group (24.1%), and the three-year recurrence rate was also lower (6.9% vs. 41.4%). Patient-specific factors such as BMI, renal morphology, and prior surgical history did not significantly affect the performance of the AcuSee system. CONCLUSIONS AND RELEVANCE: We report the first clinical application of a new navigation system for needle puncture in ultrasound-guided PCNL. It has been demonstrated that it is feasible and safe compared to the standard ultrasound-guided group in percutaneous renal puncture. This technology provides intuitive and easy-to-use visual guidance, which may facilitate safe, accurate and fast needle puncture of the kidney.

Risk Factors for Unfavorable Pathological Types of Intravesical Recurrence in Patients With Upper Urinary Tract Urothelial Carcinoma Following Radical Nephroureterectomy.

Background: Numerous studies have investigated the risk factors of intravesical recurrence (IVR) after radical nephroureterectomy (RNU) in patients with upper urinary tract urothelial carcinoma (UTUC). However, few studies explore the predictors for unfavorable pathological types of IVR following RNU. Methods: We retrospectively reviewed 155 patients diagnosed with bladder cancer (BC) following RNU. Binary logistic regression was used for the univariable and multivariable analyses. Nomograms were developed based on the multivariable analysis. The concordance index (C-index) was used to assess the performance of the nomograms. We performed internal validation by generating calibration plots. Results: Muscle-invasive BC (MIBC) was significantly correlated with operation interval (p = 0.004) and UTUC T-stage (p = 0.016). Operation interval (p = 0.002) and UTUC T-stage (p = 0.028) were also risk factors for BC > 3 cm. UTUC grade (p = 0.015), operation interval (p = 0.003), and hydronephrosis (p = 0.049) were independent predictors for high-grade BC (HGBC). MIBC (p = 0.018) and surgical approach (p = 0.003) were associated with multifocal IVR. Besides, MIBC and HGBC were associated with UTUC grade (p = 0.009), operation interval (p = 0.001), and hydronephrosis (p = 0.023). Moreover, only operation interval (p = 0.036) was a predictor for BC with at least one unfavorable pathological type. We developed nomograms for MIBC, HGBC, BC > 3 cm, and MIBC and/or HGBC. The calibration curves of the nomograms showed good agreement between the observation and prediction cases. The C-indexes of the nomograms were 0.820 (95% CI, 0.747-0.894), 0.728 (95% CI, 0.649-0.809), 0.770 (95% CI, 0.679-0.861), and 0.749 (95% CI, 0.671-0.827), respectively. Conclusions: The current study found that operation interval, UTUC T-stage, UTUC grade, surgical approach, and hydronephrosis are independent predictors for unfavorable pathological types of IVR following RNU. Nomograms based on these predictors were developed and internally validated to assess the risk of developing unfavorable pathological types of IVR. Furthermore, patients at high risk of developing unfavorable pathological types BC may benefit from more active follow-up 1 year after RNU by early detection of IVR.

The Evolution of Clinicopathological Diagnostic Features of Upper Tract Urothelial Carcinoma in China: A Summary of 2561 Cases in the Last 20 Years.

Objectives: To summarize the clinicopathological diagnostic features and evolutionary trends of upper tract urothelial carcinoma (UTUC) in China over the past 20 years. Methods: All patients diagnosed with upper tract urothelial carcinoma in the Peking University First Hospital from 2001 to 2020 were retrospectively collected. Data were divided into two groups (2001-2010 and 2011-2020) according to the date of diagnosis. Statistical analysis was done with the SPSS V22.0. Chi-square analysis and t-test were adopted to analyze depending on the data type. Subgroup analysis based on 5 years was used for visualization to present trends. Both Kaplan-Meier curve and Cox regression were used for univariate and multivariate survival analysis. Results: The study included 2561 cases diagnosed with upper tract urothelial carcinoma in total. Compared with the first decade (2001-2010), patients of the second decades (2011-2020) had elder mean age (66.65 versus 67.59, years, p=0.025), higher male proportion (43.5% versus 49.0%, p=0.034), lower incidence of renal pelvic tumors (53.4% versus 45.8%, p<0.001) and multifocality (18.6% versus 12.0%, p<0.001), higher incidence of ureteral tumors (52.2% versus 60.9%, p<0.001).In recent ten years, the incidence of muscle-invasive urothelial carcinoma (pT2+) decreased significantly (64.4% versus 54.9%, p<0.001),and the mean size of renal pelvic tumors increased(3.46 versus 3.73, cm, p=0.043). The size of the ureteral tumor, the histopathologic grade showed no significant change. The prognostic analysis based on 709 patients regularly followed at our center revealed that the male gender and G3 histopathological grade were independent risk factors for poorer prognosis in patients with UTUC. Conclusion: In the past 20 years, the clinicopathological diagnostic features of upper tract urothelial carcinoma in the Chinese population has changed significantly, suggesting an increased risk of a poorer prognosis for UTUC. This trend may be related to updating diagnostic techniques and self-monitoring awareness. However, we need more high-grade, multicenter trials to verify it in the future.

Patient-Derived Upper Tract Urothelial Carcinoma Organoids as a Platform for Drug Screening.

Upper tract urothelial carcinomas (UTUCs) are rare entities that are usually diagnosed at advanced stages. Research on UTUC pathobiology and clinical management has been hampered by the lack of models accurately reflecting disease nature and diversity. In this study, a modified organoid culture system is used to generate a library of 25 patient-derived UTUC organoid lines retaining the histological architectures, marker gene expressions, genomic landscapes, and gene expression profiles of their parental tumors. The study demonstrates that the responses of UTUC organoids to anticancer drugs can be identified and the model supports the exploration of novel treatment strategies. This work proposes a modified protocol for generating patient-derived UTUC organoid lines that may help elucidate UTUC pathophysiology and assess the responses of these diseases to various drug therapies in personalized medicine.

Should ureteroscopy be performed for patients after ureteral reconstruction with autologous onlay flap/graft?

BACKGROUND: To analyze the safety and clinical significance of performing ureteroscopy after ureteral reconstruction with autologous onlay/graft. To describe the ureteroscopic appearances of the appendiceal onlay flap and lingual mucosa graft. METHODS: Beginning in August 2018, we conducted a prospective cohort study of autologous onlay/graft techniques to repair ureteral strictures. The perioperative data of 42 patients who had undergone surgery more than 6 months prior were collected prospectively. During the postoperative follow-up, ureteroscopy was performed in 27 patients (64.3%) after surgery (group A), and ureteroscopy was not performed in the other 15 patients (35.7%) (group B). We carried out a comparative study of these two groups of patients. Analyses were conducted mainly on complications related to ureteroscopy and the success rate of ureteral reconstruction surgery. RESULTS: There were no significant differences in patient demographic data or the length of ureteral reconstruction between the two groups (P>0.05). For the ureteroscopy group, the median time from repair surgery to ureteroscopy was 3 (range, 2-7) months, there was no poor healing of the anastomosis, and the ureteral lumen of all patients was unobstructed. Some expected observations can be found in the ureteral lumen, such as mucosa edema, stones, follicles and granulation tissue. Among the 27 patients, one patient (3.7%) developed bleeding intraoperatively and 7 patients (25.9%) were found to have low-grade (Clavien-Dindo I and II) postoperative complications, including 5 cases of fever and 2 cases of bleeding. The mean follow-up times of patients in group A and group B were 16.7±6.4 and 19.0±10.1 months, respectively. The objective success (imaging showed hydronephrosis ease) rate of the two groups was 100%. The subjective success (symptom relief) rates of group A and group B were 96.3% and 100%, respectively. CONCLUSIONS: Patients after autologous onlay flap/graft ureteroplasty do not need to undergo routine ureteroscopy unless there is aggravation of hydronephrosis or other indications for ureteroscopy, such as stones.

Management of tuberculous-contracted bladder with bilateral duplex collecting system: a case report with modified robotic urinary tract reconstructive surgery.

Tuberculous bladder contracture with a bilateral duplicated collecting system is rare. According to anatomic variation, the surgical treatment strategy is highly individualized. We illustrate our robotic technique of urinary tract reconstruction. A 19-year-old girl with a history of pulmonary tuberculosis (TB) as a young child presented with a complaint of increasing frequency of micturition, nocturia, urgency, and urge incontinence starting at the age of 17. Clinical and imaging examinations demonstrated tuberculous contracted bladder with a bilateral duplex collecting system. The patient underwent a robot-assisted Institute of Urology Peking University (IUPU) orthotopic ileal neobladder reconstruction. This is a modified urinary tract reconstructive method, including resection of the end of the duplex ureters and diseased contracted bladder with preservation of the proximal urethra and bladder neck, ileal harvesting and IUPU strategy to reconstruct an ileal neobladder, uretero-ileal anastomosis and neobladder-bladder neck anastomosis. The patient remained symptom-free without recurrence of TB and had improved renal function during the one-year follow-up after surgery. Thus, our robot-assisted IUPU orthotopic ileal neobladder reconstruction method is an effective approach for this benign case. It can effectively increase bladder capacity, reduce intravesical pressure, and improve symptoms such as urination frequency and urgency.

Modified Takazawa anatomical classification of renal pelvicalyceal system based on three-dimensional virtual reconstruction models.

BACKGROUND: Previous classification of renal pelvicalyceal anatomical structure may be difficult to intuitively understand and unpractical for endourological surgery. We aim to put forward a modified Takazawa anatomical classification of renal pelvicalyceal system based on three-dimensional (3D) virtual reconstruction models for endourological surgery. METHODS: We retrospectively collected data on 225 patients (320 kidneys) in total between Apr. 2017 and Dec. 2020, spatial anatomical structure of renal pelvis and calyces were modeled and corresponding morphological parameters were measured after 3D virtual reconstruction of computed tomography urography (CTU). The modified Takazawa renal pelvicalyceal anatomical classification was advanced based on the renal pelvicalyceal morphological parameters [bifurcated branches of renal pelvis, cross sectional area of renal pelvis and ureteropelvic junction (UPJ), infundibuloureteral angle (IUA), lower pole infundibular calyceal length (IL)] by 3D virtual reconstruction models, and comparison of renal pelvicalyceal system morphological parameters were performed to evaluate the differences in various classification types of renal pelvis and calyces. RESULTS: Anatomical structure of renal pelvis and calyces were divided into two main types (Type A and Type B) according to renal pelvic branch patterns. A single pelvis without bifurcated branch was regarded as Type A (62%) and subclassified into three subtypes: Type A1 (22%), Type A2 (27%) and Type A3 (13%), the slimline pelvis was classified as Type A1, the typical pelvis as Type A2 and the broad pelvis as Type A3. A divided pelvis with bifurcated branches was seen as Type B (38%) and subclassified into two subtypes: Type B1 (15%) with the wide and flat lower calyx branch, Type B2 (23%) with the narrow and steep lower calyx branch. CONCLUSIONS: Previous studies have reported that the visualization and classification of renal pelvicalyceal anatomical structure by endocast, autopsy, ultrasonography and excretory urography, the modified Takazawa classification system based on 3D virtual reconstruction models enables to standardized different anatomical morphology of renal pelvicalyceal system and provide intuitive and concise information on anatomy, thus leading to the improvement in treatment modality.

Fluoroscopy-free minimally invasive ureteral stricture balloon dilatation: a retrospective safety and efficacy cohort study.

BACKGROUND: Traditional ureteral stricture balloon dilation was performed with fluoroscopic assistance. The use of a C-arm X-ray machine delivered hazardous radiation to both surgeons and patients. In attempt to eliminate the radiation hazard, we developed a F4.5/6.5 ureteroscope assisted intraoperative X-ray free balloon dilation surgical approach to treat ureteral stricture and to verify its safety and efficacy. Specifically, this method had not been previously reported in the literature. METHODS: We demonstrated an intraoperative X-ray free balloon dilation with detailed step-by-step procedures description and video illustration. Clinical data of patients undergoing minimally invasive endourological treatment for ureteral stricture between February 2015 and November 2019 were retrospectively analyzed. All steps of X-ray free balloon dilation were carried out under direct vision of a ureteroscope, and two indwelling F7 ureteral stents were used for 3 months postoperatively. Preoperative, intraoperative, and postoperative clinical data were evaluated, and follow-up results were reported. Successful outcome was defined as disappearance of preoperative symptoms, relief of hydronephrosis and stable of renal function. Univariate and multivariate prognostic analyses were performed. RESULTS: We identified 109 patients who received endourological treatment for ureteral stricture in our hospital's medical database. After excluding patients undergone simple catheter dilation, endoureterotomy and other treatment method, 76 patients received balloon dilation without intraoperative fluoroscopic guidance were included in our study. 4/76 patients report a grade II complication (urinary tract infections, UTIs) according to Clavien Dindo classification. In the 22.5 months median follow-up time, the one-year cumulative success rate and two-year cumulative success rate were 85.9% and 80.2% (61/76), respectively, and the majority (13/15, 86.7%) recurrence of ureteral stricture or hydronephrosis deterioration were found within two years after surgery. The longer stenotic lesion length (>5 mm) or multiple ureter stenosis and compromised blood supply of ureter were significantly associated with postoperative stenosis recurrence. CONCLUSIONS: X-ray free endoscopic balloon dilation is a safe and effective procedure that could be performed on patients with ureteral stenosis.

Minimally invasive ileal ureter replacement: Comparative analysis of robot-assisted laparoscopic versus conventional laparoscopic surgery.

BACKGROUND: This study is an initial comparative analysis of perioperative and intermediate-term functional outcomes between patients who underwent robot-assisted laparoscopic (RALS) or conventional laparoscopic surgery (LS). MATERIALS AND METHODS: A total of 25 patients who underwent ileal ureter replacement (10 RALS and 15 LS) were followed by functional cine magnetic resonance urography (MRU) combined with a modified Whitaker test. Also, the characteristics, perioperative data and functional outcomes of the patients were compared. RESULTS: The estimated blood loss, postoperative hospital stay and time to oral intake were significantly lower in the RALS group. At the median 14-month follow-up, all the patients showed improved renal function and were symptom-free, with no signs of leakage or stenosis observed by cine MRU combined with a modified Whitaker test. CONCLUSIONS: RALS with an extracorporeal bowel resection is feasible and appears to be safe, with quick postoperative recovery and encouraging outcomes.

Comparison of KD-SR-01 robotic partial nephrectomy and 3D-laparoscopic partial nephrectomy from an operative and ergonomic perspective: A prospective randomized controlled study in porcine models.

BACKGROUND: To investigate the feasibility, validity and security of a new robot platform called KD-SR-01 and compare relative merits of KD-SR-01 robotic partial nephrectomy (KD-RPN) and 3D-Laparoscopic Partial Nephrectomy (3D-LPN). METHODS: Twelve porcine models were randomly and equally divided for KD-RPN and 3D-LPN. The perioperative outcomes, physical and mental workload of the surgeon were compared. Physical workload was evaluated with surface electromyography. Mental workload was evaluated with National Aeronautics and Space Administration Task Load Index (NASA-TLX). RESULTS: All surgeries were performed successfully. The average docking time of KD-RPN was 6 min. The estimated blood loss was lower in KD-RPN (p < 0.05). There were no differences in all the other operative variables (p > 0.05). KD-RPN showed advantages in physical workload and was significantly superior in mental workload (p < 0.05). CONCLUSIONS: KD-RPN is technically feasible, valid and safe in porcine models. It's comparable from operative perspective while KD-RPN had advantages over 3D-LPN from ergonomic perspective.

The Significance of Preoperative Serum Sodium and Hemoglobin in Outcomes of Upper Tract Urothelial Carcinoma: Multi-Center Analysis Between China and the United States.

PURPOSE: To analyze the effect of preoperative serum sodium and hemoglobin on oncologic outcomes in upper tract urothelial carcinoma (UTUC) based on a multi-center cohort from China and the United States (U.S.). METHODS: We retrospectively reviewed the records of 775 patients with UTUC treated surgically at tertiary care medical facilities in China or the US from 1998 to 2015. We analyzed associations of preoperative serum sodium and hemoglobin with clinicopathological characteristics, overall survival (OS), cancer-specific survival (CSS) and intravesical recurrence free survival (IVRFS). RESULTS: The US patients had comparatively lower serum sodium and similar hemoglobin at baseline. Preoperative low serum sodium value was associated with tumor multifocality, lymph node metastasis (LNM) and lymphovascular invasion (LVI); preoperative anemia was associated with advanced age, tumor multifocality, high tumor grade and LVI. Preoperative low serum sodium was an independent predictor of worse OS in the entire cohort; preoperative anemia was an independent predictor of worse OS and CSS in the US cohort alone, Chinese cohort alone and the combined cohort. We developed a predictive nomogram for OS which exhibited better prognostic value when it included the values of sodium and anemia, and successfully validated it in different cohorts. CONCLUSION: Preoperative low serum sodium and anemia could be informative in predicting worse pathologic and survival outcomes in different UTUC patient ethnic groups.

High Preoperative Controlling Nutritional Status Score Predicts a Poor Prognosis in Patients with Localized Upper Tract Urothelial Cancer: A Propensity Score Matching Study in a Large Chinese Center.

PURPOSE: The aim of this study was to elucidate the prognostic value of the preoperative controlling nutritional status (CONUT) score, a new index based on the total lymphocyte count, serum albumin concentration and total cholesterol concentration, in patients with localized upper tract urothelial cancer (UTUC) after radical nephroureterectomy (RNU) using propensity score matching (PSM) analysis. METHODS: We retrospectively reviewed 908 consecutive patients with localized UTUC who underwent RNU between 1999 and 2015. Patients were divided into two groups according to the optimal cutoff value of the preoperative CONUT score. Relationships between the CONUT score with clinicopathological characteristics, overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) were analyzed before and after 1:1 PSM. RESULTS: A high preoperative CONUT score was significantly correlated with older age, low body mass index (BMI), poor American Statistical Association (ASA) score, advanced pathological T stage, and tumor squamous or glandular differentiation (all p<0.05). Kaplan-Meier curves showed poor OS, CSS, and DFS for patients with a high CONUT score before and after PSM (all p<0.001). Furthermore, multivariate analyses revealed that a high preoperative CONUT score was an independent risk factor for poor DFS (hazard ratio [HR] 1.418, 95% confidence interval [CI] 1.132-1.776, p=0.002) before PSM and an independent risk factor for poor DFS (HR 1.333, 95% CI 1.010-1.760, p=0.042) and OS (HR 1.459, 95% CI 1.010-2.107, p=0.044) after PSM. CONCLUSION: A high preoperative CONUT score is an independent prognostic factor for poor outcomes in patients with localized UTUC after RNU.

Prognostic Significance of Murine Double Minute 2 Expression in Tumor Cells in Upper Tract Urothelial Carcinoma: An Analysis of 341 Cases in a Large Chinese Center.

Aims: The prognostic significance of murine double minute 2 (MDM2) expression remains unknown in patients with upper tract urothelial carcinoma (UTUC). This study was designed to evaluate MDM2 expression and its association with clinicopathological characteristics and tumor outcomes in UTUC patients. Materials and Methods: Expression levels of MDM2 and p53 were determined by immunohistochemistry in a cohort of 341 UTUC patients. Associations of MDM2 and p53 expression levels with clinicopathological characteristics, disease-free survival (DFS), cancer-specific survival (CSS), and intravesical recurrence-free survival (IVRFS) were analyzed. Results: Nuclear expression of MDM2 and p53 were detected in the tumor cells of 129 (37.8%) and 203 (59.5%) patients, respectively. Decreased p53 expression was associated with positive MDM2 staining in tumor cells (p = 0.002). MDM2 expression was correlated with the exposure to aristolochic acids (p = 0.020), better preoperative renal function (p = 0.016), ureter location (p = 0.002), higher pathological T stage (p = 0.006), high tumor grade (p < 0.001), presence of glandular differentiation (p = 0.036), and sarcoma differentiation (p = 0.020). Kaplan-Meier analysis showed that positive MDM2 staining was associated with shorter CSS (p < 0.001), DFS (p < 0.001), and IVRFS (p = 0.020); MDM2+/p53- was associated with shorter CSS (p < 0.001) and DFS (p < 0.001), but not IVRFS (p = 0.145); while CSS, DFS, and IVRFS did not differ significantly between the p53+ and p53- patients (p = 0.307, 0.089, and 0.198, respectively). Multivariate analyses revealed that MDM2 expression in tumor cells independently predicted shorter CSS (p < 0.001; hazard ratio [HR] = 2.600; 95% confidence interval [CI]: 1.625-4.161) and DFS (p < 0.001; HR = 1.863; 95% CI: 1.314-2.641), excepting IVRFS (p = 0.092; HR = 1.590; 95% CI: 0.928-2.726). Conclusions: UTUC patients with elevated MDM2 expression may exhibit more aggressive biological features of the tumor and tend to have shorter CSS and DFS.

Prognostic performance of the 1973 and 2004 WHO grading classification in upper tract urothelial carcinoma.

BACKGROUND: Grading of upper tract urothelial carcinoma (UTUC) is routinely used in clinical practice; however, reports concerning prognostic performance of different grading systems are contradictory. We aim to assess the clinical reliability of the 1973 and 2004 World Health Organization (WHO) grading classification systems in UTUC. PATIENTS AND METHODS: We retrospectively evaluated 458 consecutive patients with UTUC from 2008 to 2013. The postoperative tumor grades were evaluated by a single uropathologist using the 1973 and 2004 WHO grade classification systems. The Kaplan-Meier method was used to estimate cancer-specific survival (CSS) and overall survival (OS). Univariate and multivariate analyses were used to test the association between clinical variables and the CSS and OS rates. RESULTS: There were 133 (29.0%) low-grade patients and 325 (71.0%) high-grade patients. The 3-year CSS rates were 87.0% and 76.0% for G2 and G3 disease and 89.0% and 80.0% for low- and high-grade disease according to the 2004 system, respectively. For all UTUC patients, there were significant differences in the CSS and OS rates between G2 and G3 cases, as well as between the low- and high-grade groups. The CSS and OS rates were significantly different between the G2 and G3 cases for the overall high-grade population (CSS: P = 0.003; OS: P = 0.009), while no significant difference emerged between low- and high-grade tumors in G2 UTUC patients (CSS: P = 0.717; OS: P = 0.280). In the subgroup of high-grade non-muscle-invasive tumors, the 1973 WHO grading system was an independent predictor of CSS (P = 0.045). CONCLUSIONS: The results support the hypothesis that the 1973 WHO system is superior to the 2004 system for predicting clinical outcomes in patients with non-muscle-invasive UTUC.

The role of tumor size, ultrasonographic findings, and serum tumor markers in predicting the likelihood of malignant testicular histology.

The clinical predictive factors for malignant testicular histology remain unclear because of the low prevalence. Therefore, the aim of this study was to investigate predictors of malignant histology for testicular masses and decide more testis-sparing surgeries before surgery. This retrospective study enrolled 325 consecutive testicular mass patients who underwent radical orchiectomy (310/325) or testicular preserving surgery (15/325) from January 2001 to June 2016. The clinicopathological factors, including tumor diameter, cryptorchidism history, ultrasound findings, serum alpha-fetoprotein, and human chorionic gonadotropin (HCG) levels, were collected retrospectively for statistical analysis. A predictive nomogram was also generated to evaluate the quantitative probability. Among all patients, 247 (76.0%) were diagnosed with a malignant testicular tumor and 78 (24.0%) with benign histology. Larger tumor diameter (per cm increased, hazard ratio [HR] = 1.284, P = 0.036), lower ultrasound echo (HR = 3.191, P = 0.001), higher ultrasound blood flow (HR = 3.320, P < 0.001), and abnormal blood HCG (HR = 10.550, P < 0.001) were significant predictive factors for malignant disease in all testicular mass patients. The nomogram generated was well calibrated for all predictions of malignant probability, and the accuracy of the model nomogram measured by Harrell's C statistic (C-index) was 0.92. According to our data, the proportion of patients who underwent radical orchiectomy for benign tumors (24.0%) was much larger than generally believed (10.0%). Our results indicated that the diameter, ultrasonic echo, ultrasonic blood flow, and serum HCG levels could predict the malignancy in testicular mass patients.

Segmental ureterectomy can be performed safely in patients with urothelial carcinoma of distal ureter.

INTRODUCTION: We aimed to compare oncological outcomes by surgery type (segmental ureterectomy [SU] vs. radical nephroureterectomy [RNU]) in a large cohort of patients with upper tract urothelial carcinoma (UTUC) of the distal ureter. METHODS: We performed a retrospective analysis of 219 patients with UTUC of the distal ureter among 931 patients with UTUC who underwent SU and RNU. Clinicopathological outcomes were evaluated. Cancer-specific survival (CSS), overall survival (OS), local recurrence-free survival (RFS), intravesical recurrence-free survival (IVRFS), contralateral recurrence-free survival, and distal metastasis-free survival were assessed by the Kaplan-Meier method and Cox regression, estimating hazard ratios (HR) and 95% confidence intervals (CIs). RESULTS: A total of 179 (81.7%) patients underwent RNU and 40 (18.3%) underwent SU: 85 males (47.5%) with RNU and 17 (42.5%) with SU (p=0.568). The median age with RNU and SU was 71 years (range 31-86) and 70 years (range 46-90), respectively (p=0.499). The T stage of the two groups did not differ (p=0.122), nor did mean tumour length (3.35±2.62 vs. 3.25±2.14; p=0.953), grade (p=0.075), tumour necrosis (p=0.634), or followup time (months) (58.1±8.1 vs. 63.7±3.4; p=0.462). The two groups did not differ in CSS (p=0.358) or OS (p=0.206), and surgery type did not predict CSS (HR 0.862; 95% CI 0.469-1.585; p=0.633) or OS (HR 0.764; 95% CI 0.419-1.392; p=0.379). Local RFS was higher with RNU than SU (96.2% vs. 86.0%; p=0.02), but the groups did not differ in IVRFS (p=0.661), contralateral RFS (p=0.183), or distant metastasis-free survival (p=0.078). On multivariate analysis, SU was associated with local RFS (HR 5.069; 95% CI 1.029-24.968; p=0.046) and distant metastasis-free survival (HR 6.497; 95% CI 1.196-35.283; p=0.03). Local RFS was lower with SU than RNU for patients with pT3-4 stage (p=0.006). CONCLUSIONS: Long-term oncological outcomes were equivalent with SU and RNU in patients with UTUC of the distal ureter. SU affected local recurrence survival, especially with advanced tumour stage, and distant metastasis survival.

Prevalence, clinicopathological features, and prognosis in upper tract urinary carcinoma patients with severe preoperative chronic kidney disease.

BACKGROUND: Studies regarding the prevalence and factors associated with severe pre-operative chronic kidney disease (CKD) in upper tract urinary carcinoma (UTUC) patients were rare due to the low prevalence of UTUC. We conducted the present study to investigate the prevalence, clinicopathological features, and prognosis in UTUC patients with severe preoperative CKD. METHODS: The study included 731 patients with UTUC treated with radical nephroureterectomy (RNU) in a large Chinese center. Estimated glomerular filtration rate (eGFR) was calculated by re-expressed Modification of Diet in Renal Disease (MDRD) formulas for the Chinese population. Severe preoperative CKD was defined as CKD stage 4-5 (eGFR <30 mL/min). Relationships of CKD stage 4-5 with clinicopathological characteristics, overall survival (OS), cancer-specific survival (CSS), contralateral recurrence-free survival and intravesical recurrence (IVR)-free survival were analyzed. RESULTS: A total of 73 (10.0%) patients presented severe preoperative CKD in this cohort. Multivariate logistic analysis indicated that female gender (OR =1.791; 95% CI: 1.018-3.150; P=0.043), lower BMI (OR =0.452; 95% CI: 0.262-0.778; P=0.004), concomitant bladder tumor (OR =2.944; 95% CI: 1.360-6.373; P=0.006), lower pathological T stage (OR =0.578; 95% CI: 0.339-0.984; P=0.043), tumor necrosis (OR =2.764; 95% CI: 1.411-5.416; P=0.003), and exposure of aristolochic acid (AA) (OR =3.115; 95% CI: 1.536-6.316; P=0.002) were significantly related to severe CKD. Multivariate Cox's regression analysis showed that severe preoperative CKD was significantly associated with worse OS (HR =1.840; 95% CI: 1.150-2.944; P=0.011) and worse contralateral recurrence-free survival (HR =3.269; 95% CI: 1.607-6.650; P=0.001), while no statistical difference in terms of CSS or IVR-free survival were noticed. CONCLUSIONS: Female gender, lower BMI, concomitant bladder tumor, lower pathological T stage, exposure of AA, and tumor necrosis were independently associated with severe preoperative CKD in UTUC patients. UTUC patients with severe preoperative CKD possess worse OS and higher possibility of contralateral upper urinary tract recurrence.

Aristolochic acid containing herbs induce gender-related oncological differences in upper tract urothelial carcinoma patients.

BACKGROUND: In China, upper tract urothelial carcinoma (UTUC) is less prevalent but more malignant in males. This study investigates the prognostic factors and causes of gender-based differences in Chinese populations. METHODS: Between 1999 and 2011, 687 UTUC patients who underwent surgery were utilized for this study. We evaluated the differences in oncological characteristics, epigenetic biomarkers, cancer-specific survival (CSS), bladder recurrence (BR) rate, and contralateral upper tract recurrence (CUTR) rate. Smoking history, benzene exposure history, and the history of using aristolochic acid (AA) containing herbs were analyzed in detail. RESULTS: Compared with male patients, female patients showed poorer renal function, lower proportions of tumor stage III/IV, and smaller tumor diameters. The CSS in male patients was lower than that in female patients. Significant gender-related differences were observed concerning various prognostic factors. In female patients, poorer survival rates were attributed to the primary tumor location in the ureter, large diameter primary tumors, severe chronic kidney disease, papillary tumor architecture, high tumor stages, positive N status, and methylated ABCC6 promoters. In male patients, older age, ipsilateral hydronephrosis, large tumor diameters, sessile tumor architecture, high tumor stages, and methylated TMEFF2 promoters were associated with higher cancer-specific mortality. AA might be the main cause of these gender-based differences. The AA-induced UTUC patients presented smaller tumor diameters, lower tumor stages, fewer positive N statuses, more multifocal tumors, lower methylation indices, and poorer renal function. Although AA-induced UTUC patients exhibited better survival rates, BR and CUTR rates were significantly worse. CONCLUSION: In China, there exist significant AA-induced differences between male and female UTUC patients. The bladders and contralateral upper urinary tracts of AA-induced UTUC patients should be carefully monitored after surgery.