Efficacy of Mitomycin C Combined with Direct Vision Internal Urethrotomy for Urethral Strictures: A Systematic Review and Meta-Analysis.

BACKGROUND: The high recurrence of a urethral stricture after direct vision internal urethrotomy (DVIU) has been a problem for years. Mitomycin C (MMC) is an excellent antifibrosis antigen that has been used in many fields, but its effect on a urethral stricture remains controversial. The purpose of this review was to investigate the effectiveness of MMC in reducing the recurrence rate of a urethral stricture after the first urethrotomy. METHODS: Common databases were searched for publications prior to November 30, 2020. Randomized controlled and cohort trials were all included. Recurrence and success rates after the first urethrotomy of the posterior urethra were the main outcomes. Revman 5.3 was used for statistical analysis. Two evaluation systems, the Cochrane risk of bias tool and the Newcastle Ottawa Scale, were used to examine the risk of bias for RCTs and all studies. The quality of evidence was assessed by the Grading of Recommendations, Assessment, Development, and Evaluation standard. RESULTS: Sixteen trials were included, the reporting quality of which was generally poor, and the evidence level was very low to moderate. The addition of MMC could significantly reduce the recurrence rate of urethral strictures (risk ratio [RR] = 0.42; 95% confidence interval [CI]: 0.26, 0.67; p = 0.0002; 9 trials; 550 participants). The results of the subgroup analysis suggested that the effect of MMC combined with DVIU was significant in short (≤2 cm) anterior urethral strictures (RR = 0.39; 95% CI: 0.20, 0.78; p = 0.008), >12-month follow-up (RR = 0.45; 95% CI: 0.26, 0.76; p = 0.003). It also increased the success rate of the first urethrotomy procedure for posterior urethral contracture (RR = 0.74; 95% CI: 0.65, 0.84; p < 0.00001; 7 trials; 342 participants). Low-dose local injection of MMC was the most commonly used method. CONCLUSION: MMC combined with DVIU is a promising way to reduce the long-term recurrence rate of a short-segment anterior urethral stricture. It also increases the success rate of the first urethrotomy of the posterior urethra. However, more high-quality randomized controlled trials are needed.

DNA methylation subtypes guiding prognostic assessment and linking to responses the DNA methyltransferase inhibitor SGI-110 in urothelial carcinoma.

BACKGROUND: At present, the extent and clinical relevance of epigenetic differences between upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) remain largely unknown. Here, we conducted a study to describe the global DNA methylation landscape of UTUC and UCB and to address the prognostic value of DNA methylation subtype and responses to the DNA methyltransferase inhibitor SGI-110 in urothelial carcinoma (UC). METHODS: Using whole-genome bisulfite sequencing (n = 49 samples), we analyzed epigenomic features and profiles of UTUC (n = 36) and UCB (n = 9). Next, we characterized potential links between DNA methylation, gene expression (n = 9 samples), and clinical outcomes. Then, we integrated an independent UTUC cohort (Fujii et al., n = 86) and UCB cohort (TCGA, n = 411) to validate the prognostic significance. Furthermore, we performed an integrative analysis of genome-wide DNA methylation and gene expression in two UC cell lines following transient DNA methyltransferase inhibitor SGI-110 treatment to identify potential epigenetic driver events that contribute to drug efficacy. RESULTS: We showed that UTUC and UCB have very similar DNA methylation profiles. Unsupervised DNA methylation classification identified two epi-clusters, Methy-High and Methy-Low, associated with distinct muscle-invasive statuses and patient outcomes. Methy-High samples were hypermethylated, immune-infiltrated, and enriched for exhausted T cells, with poor clinical outcome. SGI-110 inhibited the migration and invasion of Methy-High UC cell lines (UMUC-3 and T24) by upregulating multiple antitumor immune pathways. CONCLUSIONS: DNA methylation subtypes pave the way for predicting patient prognosis in UC. Our results provide mechanistic rationale for evaluating SGI-110 in treating UC patients in the clinic.

Clinical, Pathological, and Prognostic Analysis of Urachal Carcinoma.

OBJECTIVE: The aim of this study was to improve understanding the clinical, pathologic, and prognostic features of urachal carcinoma (UrC), a retrospectively descriptive study was done in 2 clinical centers. METHODS: After excluding the 2 missed patients, the clinical and pathological data of 59 patients with UrC, who were diagnosed or treated at 2 clinical centers between 1986 and 2019, was retrospectively analyzed. SPSS 22.0 (IBM) and GraphPad Prism 8.0.1 were used for statistics and data visualization. Survival data were analyzed by the Kaplan-Meier method and Log-rank tests. Cox proportional hazards regression were performed for find risk factors on predicting the prognosis. RESULTS: Of all 59 patients, 47 were male and 12 were female. The median age at diagnosis was 51.6 years (range: 22-84 years). Gross hematuria was the most common symptom (79.66%). The majority of urachal neoplasms were adenocarcinomas (94.92%). Forty-two patients (72.41%) underwent extended partial cystectomy with en bloc resection of the entire urachus. The mean follow-up was 52 months (3-277 months). Median overall survival was 52.8 months (4-93 months). The 3-year cancer-specific survival (CSS) rate and 5-year CSS rate were 69.1% and 61.2%. There was no significant difference among localized T stage, tumor histologic grade and surgical procedures in determining prognosis by survival analyze. While patients with high-risk TNM stage (local abdominal metastasis, lymph node metastasis, or distant metastasis) (p = 0.003) and positive surgical margin (p < 0.001) had significantly worse prognosis. CONCLUSIONS: The results indicate that high-risk TNM stage and positive surgical margin are risk predictors of prognosis. Localized T stage, histologic grade, and surgical procedure cause no significant effect on patient prognosis. The extended partial cystectomy is the recommended surgical approach for patients with UrC. Active multimodal treatments may improve the survival of patients with recurrent and metastatic disease.

CTRP3 attenuates cardiac dysfunction, inflammation, oxidative stress and cell death in diabetic cardiomyopathy in rats.

AIMS/HYPOTHESIS: Oxidative stress, inflammation and cell death are closely involved in the development of diabetic cardiomyopathy (DCM). C1q/tumour necrosis factor-related protein-3 (CTRP3) has anti-inflammatory properties but its role in DCM remains largely unknown. The aims of this study were to determine whether CTRP3 could attenuate DCM and to clarify the underlying mechanisms. METHODS: Streptozotocin (STZ) was injected intraperitoneally to induce diabetes in Sprague-Dawley rats. Cardiomyocyte-specific CTRP3 overexpression was achieved using an adeno-associated virus system 12 weeks after STZ injection. RESULTS: CTRP3 expression was significantly decreased in diabetic rat hearts. Knockdown of CTRP3 in cardiomyocytes at baseline resulted in increased oxidative injury, inflammation and apoptosis in vitro. Cardiomyocyte-specific overexpression of CTRP3 decreased oxidative stress and inflammation, attenuated myocyte death and improved cardiac function in rats treated with STZ. CTRP3 significantly activated AMP-activated protein kinase α (AMPKα) and Akt (protein kinase B) in H9c2 cells. CTRP3 protected against high-glucose-induced oxidative stress, inflammation and apoptosis in vitro. AMPKα deficiency abolished the protective effects of CTRP3 in vitro and in vivo. Furthermore, we found that CTRP3 activated AMPKα via the cAMP-exchange protein directly activated by cAMP (EPAC)-mitogen-activated protein kinase kinase (MEK) pathway. CONCLUSIONS/INTERPRETATION: CTRP3 protected against DCM via activation of the AMPKα pathway. CTRP3 has therapeutic potential for the treatment of DCM.

Arctiin protects against cardiac hypertrophy through inhibiting MAPKs and AKT signaling pathways.

PURPOSE: The mitogen-activated protein kinases (MAPKs) and protein kinase B (AKT) pathways have emerged as essential intracellular signaling pathways in eukaryotic cells, particularly as regulators of cardiac hypertrophy. Previous studies indicated that arctiin, an active ingredient of biennial dried ripe burdock, could exhibit potent anti-inflammatory and anti-allergic activities via down-regulating the activation of MAPKs and AKT pathways. However, little is known about its effects on cardiac hypertrophy. Therefore, the present study aimed to explore whether arctiin could attenuate cardiac hypertrophy. GENERAL METHODS: Arctiin (80 mg/kg) was administered by oral gavage once daily for 3 weeks from 1 week after surgery. Then, the mice were subjected to either chronic pressure overload generated by aortic banding (AB) or sham surgery (control group). Cardiac function was assessed by echocardiography. FINDINGS: The results indicated that arctiin attenuated cardiac hypertrophy induced by AB, and suppressed cardiac fibrosis and accumulation of collagen in vivo. Arctiin also inhibit the activation of MAPKs and AKT occurs in response to hypertrophic stimuli. Arctiin attenuated phenylephrine-induced hypertrophy of myocytes in vitro. CONCLUSIONS: In conclusion, arctiin can improve cardiac function and prevent the development of cardiac hypertrophy by blocking the MAPKs and AKT signaling pathways.

Prognostic value of tumor-stroma ratio in clear cell renal cell carcinoma after surgery.

Background: Clear cell renal cell carcinoma (ccRCC) is one of the most common urological tumors, and its incidence is increasing year by year. Tumor stroma ratio (TSR) can reflect the amount of stromal component around tumor cells, and can independently predict the prognosis of tumor. This study aims to evaluate the prognostic value of TSR in ccRCC patients. Methods: From January 2010 to December 2015, clinical and histopathological data of patients with ccRCC patients who underwent surgical operation were collected. Using TSR (50%) as the cut-off value, the patients were divided into low-TSR group (<50%) and high-TSR group (≥50%). The clinicopathological characteristics and survival status of patients were compared between the two groups. Univariate and multivariate analyses were used to identify the prognostic factors for overall survival (OS), cancer-specific survival (CSS), metastasis-free survival (MFS). Results: The mean age of 569 patients was 56.84±12.76 years old. There were 401 males and 168 females. According to the TSR, patients were divided into low-TSR group (n=333, 58.5%) and high-TSR group (n=236, 41.5%). The median follow-up time was 67.0 months (interquartile range, 33.0-72.0 months). The 5-year OS, CSS and MFS were 91.2%, 94.6% and 91.0%, respectively. The 5-year OS, CSS and MFS were 84.2%,89.7% and 82.7% in the high-TSR group and 96.1%, 98.0% and 96.0% in the low-TSR group (P<0.05). Multivariate analysis showed that age >60 years [hazard ratio (HR) =2.455, 95% confidence interval (CI): 1.292-4.668, P=0.006), tumor grade (HR =6.580, 95% CI: 3.276-13.216, P<0.001) and TSR (HR =2.611, 95% CI: 1.265-5.387, P=0.009) were independent prognostic factors for OS. Multivariate analysis showed that tumor stage (HR =3.213, 95% CI: 1.437-7.184, P=0.004), tumor grade (HR =6.102, 95% CI: 2.664-13.976, P<0.001) and TSR (HR =2.653, 95% CI: 1.063-6.621, P=0.03) were independent prognostic factors for CSS. Multivariate analysis showed that tumor stage (HR =4.805, 95% CI: 2.677-8.624, P<0.001), tumor grade (HR =6.423, 95% CI: 3.432-12.020, P<0.001), hemorrhage (HR =0.514, 95% CI: 0.265-0.996, P=0.049) and TSR (HR =2.370, 95% CI: 1.264-4.443, P=0.007) were independent prognostic factors for MFS. Conclusions: TSR is a new independent prognostic risk factor for ccRCC patients. The assessment of TSR is simple and cost-effective, and it is a useful supplement added to the pathological evaluation system.

Balloon dilation for the treatment of male urethral strictures: a systematic review and meta-analysis.

OBJECTIVE: The use of minimally invasive endoluminal treatment for urethral strictures has been a subject for debate for several decades. The aim of this study was to review and discuss the safety, efficacy and factors influencing the clinical application of balloon dilation for the treatment of male urethral strictures. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Embase, Medline, Web of Science, Cochrane Library and Scopus were searched for publications published before 17 July 2022. STUDY SELECTION: Two independent researchers screened and assessed the results, and all clinical studies on balloon dilation for the treatment of urethral strictures in men were included. DATA EXTRACTION AND SYNTHESIS: The success rate, rate of adverse events, International Prostate Symptom Scores, maximum uroflow (Qmax) and postvoid residual urine volume were the main outcomes. Stata V.14.0 was used for statistical analysis. RESULTS: Fifteen studies with 715 patients were ultimately included in this systematic review. The pooled results of eight studies showed that the reported success rate of simple balloon dilation for male urethral strictures was 67.07% (95% confidence interval [CI]: 55.92% to 77.36%). The maximum urinary flow rate at 3 months (risk ratio [RR]= 2.6510, 95% CI: 1.0681 to 4.2338, p<0.01) and the maximum urinary flow rate at 1 year (RR= 1.6637, 95% CI: 1.1837 to 2.1437, p<0.05) were significantly different after dilation. There is insufficient evidence to suggest that balloon dilation is superior to optical internal urethrotomy or direct visual internal urethrotomy (DVIU) (RR= 1.4754, 95% CI: 0.7306 to 2.9793, p=0.278). CONCLUSION: Balloon dilation may be an intermediate step before urethroplasty and is a promising alternative therapy to simple dilation and DVIU. The balloon is a promising drug delivery tool, and paclitaxel drug-coated balloon dilation is effective in reducing retreatment rates in patients with recurrent anterior urethral strictures. The aetiology, location, length, previous treatment of urethral stricture may be associated with the efficacy of balloon dilation. PROSPERO REGISTRATION NUMBER: CRD42022334403.

The Regenerative Microenvironment of the Tissue Engineering for Urethral Strictures.

Urethral stricture caused by various reasons has threatened the quality of life of patients for decades. Traditional reconstruction methods, especially for long-segment injuries, have shown poor outcomes in treating urethral strictures. Tissue engineering for urethral regeneration is an emerging concept in which special designed scaffolds and seed cells are used to promote local urethral regeneration. The scaffolds, seed cells, various factors and the host interact with each other and form the regenerative microenvironment. Among the various interactions involved, vascularization and fibrosis are the most important biological processes during urethral regeneration. Mesenchymal stem cells and induced pluripotent stem cells play special roles in stricture repair and facilitate long-segment urethral regeneration, but they may also induce carcinogenesis and genomic instability during reconstruction. Nevertheless, current technologies, such as genetic engineering, molecular imaging, and exosome extraction, provide us with opportunities to manage seed cell-related regenerative risks. In this review, we described the interactions among seed cells, scaffolds, factors and the host within the regenerative microenvironment, which may help in determining the exact molecular mechanisms involved in urethral stricture regeneration and promoting clinical trials and the application of urethral tissue engineering in patients suffering from urethral stricture.

Impact of tumour stroma-immune interactions on survival prognosis and response to neoadjuvant chemotherapy in bladder cancer.

BACKGROUND: The tumour stroma is associated with unfavourable prognosis in diverse solid tumours, but its prognostic and predictive value in bladder cancer (BCa) is unclear. METHODS: In this multicentre, retrospective study, we included 830 patients with BCa from six independent cohorts. Differences in overall survival (OS) and cancer-specific survival (CSS) were investigated between high-tumour stroma ratio (TSR) and low-TSR groups. Multi-omics analyses, including RNA sequencing, immunohistochemistry, and single-cell RNA sequencing, were performed to study stroma-immune interactions. TSR prediction models were developed based on pelvic CT scans, and the best performing model was selected based on receiver operator characteristic analysis. FINDINGS: Compared to low-TSR tumours, high-TSR tumours were significantly associated with worse OS (HR = 1.193, 95% CI: 1.046-1.361, P = 0.008) and CSS (HR = 1.337, 95% CI: 1.139-1.569, P < 0.001), and lower rate of pathological complete response (pCR) to neoadjuvant chemotherapy (NAC). High-TSR tumours exhibited higher infiltration of immunosuppressive cells, including Tregs and tumour-associated neutrophils, while low-TSR tumours exhibited higher infiltration of immune-activating cells such as CD8+ Teff and XCR1+ dendritic cells. The TSR prediction model was developed by combining the intra-tumour and tumour base radiomics features, and showed good performance to predict high-TSR, as indicted by area under the curve of 0.871 (95% CI: 0.821-0.921), 0.821 (95% CI: 0.731-0.911), and 0.801 (95% CI: 0.737-0.865) in the training, internal validation, and external validation cohorts, respectively. In patients with low predicted TSR, 92.3% (12/13) achieved pCR, while only 35.3% (6/17) of patients with high predicted TSR achieved pCR. INTERPRETATION: The tumour stroma was found to be significantly associated with clinical outcomes in patients with BCa as a result of tumour stroma-immune interactions. The radiomics prediction model provided non-invasive evaluation of TSR and was able to predict pCR in patients receiving NAC for BCa. FUNDING: This work was supported by National Natural Science Foundation of China (Grant No. 82373254 and 81961128027), Guangdong Provincial Natural Science Foundation (Grant No. 2023A1515010258), Science and Technology Planning Project of Guangdong Province (Grant No. 2023B1212060013). Science and Technology Program of Guangzhou (SL2022A04J01754), Sun Yat-Sen Memorial Hospital Clinical Research 5010 Program (Grant No. SYS-5010Z-202401).

The effect of music therapy on delirium in patients receiving mechanical ventilatory support in the Intensive Care Unit: A protocol for systematic review and meta-analysis.

BACKGROUND: Delirium is a very common sick syndrome in patients receiving mechanical ventilatory support in the Intensive Care Unit (ICU). Music therapy is a promising non-pharmacological intervention. However, its effect on the duration, incidence and severity of delirium is unknown. So we will perform a systematic review and meta-analysis to evaluate the effect of music therapy on delirium in patients receiving mechanical ventilatory support in the ICU. METHODS: This systematic review was registered in the PROSPERO. We will follow the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocol to accomplish the systematic review protocol. Searches of PubMed, EMbase, the Cochrane library, CBM, CNKI and Wanfang databases will be conducted through computer to collect randomized controlled trials (RCTs) on the effects of music therapy on delirium in patients receiving mechanical ventilatory support in the ICU. The search time will be all from database establishment to April 2023. Two evaluators will independently screen the literature, extract information and evaluate the risk of bias of included studies, then data analysis will be performed using Stata 14.0 software. RESULTS: The results of this systematic review and meta-analysis will be publicly available and published in a peer-reviewed journal. CONCLUSION: This study will provide evidence-based medical evidence for music therapy to control delirium in patients receiving mechanical ventilatory support in the ICU.

Surgical techniques and oncological outcomes of pure transperitoneal laparoscopic radical nephroureterectomy for upper urinary tract urothelial carcinoma.

Background: Open radical nephroureterectomy (RNU) with bladder cuff excision is the standard treatment for upper urinary tract urothelial carcinoma (UTUC). Traditional laparoscopic radical nephroureterectomy (LSRNU) is not minimally invasive enough due to the complex surgical procedure. This study aims to discuss the clinical feasibility and oncological outcomes of pure transperitoneal LSRNU for UTUC. Methods: Between July 2010 and December 2020, 115 patients were admitted to the hospital with the diagnosis of UTUC treated with pure LSRNU by one surgeon. A special laparoscopic bulldog clamp was placed at the bladder cuff before cutting and suturing. The clinical and follow-up data were preoperatively collected and analyzed. Overall survival (OS) and cancer-specific survival (CSS) were estimated by the Kaplan-Meier method. Results: All surgeries were completed uneventfully in this cohort. The mean operative time was 145.69 minutes. The mean estimated blood loss was 56.61 mL. The mean removal time of the drain was 3.46 days. The mean time of having liquid diet was 1.32 days, and the ambulation time was 1.50 days. All surgeries were effectively completed, and no case required open conversion. According to the Clavien-Dindo classification system, postoperative complications occurred in two patients (II, III). The mean length of postoperative hospital stay was 5.78 days. The mean follow-up duration was 54.50 months. Recurrence in the bladder was 16.0% (15/94), compared with 4.6% (4/87) in the contralateral upper tract. The 5-year OS and CSS rates were 78.9% and 81.4%, respectively. Conclusions: Pure transperitoneal LSRNU is a safe and effective minimally invasive technology for the treatment of UTUC.

Totally Intracorporeal Robot-assisted Unilateral or Bilateral Ileal Ureter Replacement for the Treatment of Ureteral Strictures: Technique and Outcomes from a Single Center.

BACKGROUND: Few studies on totally intracorporeal robot-assisted ileal ureter replacement (RA-IUR) have been reported. OBJECTIVE: To report our technique and the outcomes of totally intracorporeal RA-IUR for unilateral or bilateral ureteral reconstruction, involving performing cystoplasty simultaneously. DESIGN, SETTING, AND PARTICIPANTS: Fifteen patients underwent totally intracorporeal RA-IUR from April 2021 to July 2022 at a single center. The perioperative variables were prospectively collected, and the outcomes were assessed. SURGICAL PROCEDURE: The surgical procedure included dissection of the proximal end of the ureteral stricture or renal pelvis, harvesting of the ileal ureter, rebuilding of intestinal continuity, upper anastomosis of the ileum to the renal pelvis or the ureteral end, and lower anastomosis of the ileum to the bladder. All operations were performed intracorporeally. MEASUREMENTS: Patient demographics and perioperative results were prospectively collected and analyzed for perioperative complications and success rates. A descriptive statistical analysis was performed. RESULTS AND LIMITATIONS: All patients successfully underwent totally intracorporeal RA-IUR without open conversion. Seven patients received unilateral RA-IUR and eight received bilateral RA-IUR. The mean (range) length of the harvested ileal segment was 28.3 (15-40) cm, the operative duration was 261.8 (183-381) min, the estimated blood loss was 64.7 (30-100) ml, and the duration of postoperative hospitalization was 10.5 (7-17) d. At a median (range) follow-up of 14 (8-22) mo, the subjective and functional success rates were 100% and 86.7%, respectively. CONCLUSIONS: Our results demonstrate that totally intracorporeal unilateral or bilateral RA-IUR (even with ileocystoplasty) can be performed safely and efficiently with acceptable minor complications and a high success rate. PATIENT SUMMARY: Our study indicates that totally intracorporeal robotic ileal ureter replacement surgery is safe and feasible for ureteral reconstruction, even with ileocystoplasty. The postoperative complications are acceptable. At a median follow-up of 14 (8-22) mo, the subjective and functional success rates were 100% and 86.7%, respectively.

Adipose stem cells in tissue regeneration and repair: From bench to bedside.

ADSCs are a large number of mesenchymal stem cells in Adipose tissue, which can be applied to tissue engineering. ADSCs have the potential of multi-directional differentiation, and can differentiate into bone tissue, cardiac tissue, urothelial cells, skin tissue, etc. Compared with other mesenchymal stem cells, ADSCs have a multitude of promising advantages, such as abundant number, accessibility in cell culture, stable function, and less immune rejection. There are two main methods to use ADSCs for tissue repair and regeneration. One is to implant the "ADSCs-scaffold composite" into the injured site to promote tissue regeneration. The other is cell-free therapy: using ADSC-exos or ADSC-CM alone to release a large number of miRNAs, cytokines and other bioactive substances to promote tissue regeneration. The tissue regeneration potential of ADSCs is regulated by a variety of cytokines, signaling molecules, and external environment. The differentiation of ADSCs into different tissues is also induced by growth factors, ions, hormones, scaffold materials, physical stimulation, and other factors. The specific mechanisms are complex, and most of the signaling pathways need to be further explored. This article reviews and summarizes the mechanism and clinical application of ADSCs in tissue injury repair so far, and puts forward further problems that need to be solved in this field, hoping to provide directions for further research in this field.

Preoperative Prediction of Inferior Vena Cava Wall Invasion of Tumor Thrombus in Renal Cell Carcinoma: Radiomics Models Based on Magnetic Resonance Imaging.

Objective: To develop radiomics models to predict inferior vena cava (IVC) wall invasion by tumor thrombus (TT) in patients with renal cell carcinoma (RCC). Methods: Preoperative MR images were retrospectively collected from 91 patients with RCC who underwent radical nephrectomy (RN) and thrombectomy. The images were randomly allocated into a training (n = 64) and validation (n = 27) cohort. The inter-and intra-rater agreements were organized to compare masks delineated by two radiologists. The masks of TT and IVC were manually annotated on axial fat-suppression T2-weighted images (fsT2WI) by one radiologist. The following models were trained to predict the probability of IVC wall invasion: two radiomics models using radiomics features extracted from the two masks (model 1, radiomics model_IVC; model 2, radiomics model_TT), two combined models using radiomics features and radiological features (model 3, combined model_IVC; model 4, combined model_TT), and one radiological model (model 5) using radiological features. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were applied to validate the discriminatory effect and clinical benefit of the models. Results: Model 1 to model 5 yielded area under the curves (AUCs) of 0.881, 0.857, 0.883, 0.889, and 0.769, respectively, in the validation cohort. No significant differences were found between these models (p = 0.108-0.951). The dicision curve analysis (DCA) showed that the model 3 had a higher overall net benefit than the model 1, model 2, model 4, and model 5. Conclusions: The combined model_IVC (model 3) based on axial fsT2WI exhibited excellent predictive performance in predicting IVC wall invasion status.

Comprehensive genomic profiling of upper tract urothelial carcinoma and urothelial carcinoma of the bladder identifies distinct molecular characterizations with potential implications for targeted therapy & immunotherapy.

Backgrounds: Despite the genomic landscape of urothelial carcinomas (UC) patients, especially those with UC of bladder (UCB), has been comprehensively delineated and associated with pathogenetic mechanisms and treatment preferences, the genomic characterization of upper tract UC (UTUC) has yet to be fully elucidated. Materials and methods: A total of 131 Chinese UTUC (74 renal pelvis & 57 ureter) and 118 UCB patients were enrolled in the present study, and targeted next-generation sequencing (NGS) of 618 cancer-associated genes were conducted to exhibit the profile of somatic and germline alterations. The COSMIC database, including 30 mutational signatures, were utilized to evaluate the mutational spectrums. Moreover, TCGA-UCB, MSKCC-UCB, and MSKCC-UTUC datasets were retrieved for preforming genomic alterations (GAs) comparison analysis between Western and Chinese UC patients. Results: In our cohort, 93.98% and 56.63% of UC patients were identified with oncogenic and actionable somatic alterations, respectively. Meanwhile, 11.24% of Chinese UC patients (of 14.50% and 7.63% of UTUC and UCB cases, respectively) were identified to harbor a total of 32 pathogenic/likely-pathogenic germline variants in 22 genes, with DNA damage repair (DDR)-associated BRCA1 (1.20%) and CHEK2 (1.20%) being the most prevalent. Chinese UTUC and UCB patients possessed distinct somatic genomic characteristics, especially with significantly different prevalence in KMT2D/C/A, GNAQ, ERCC2, RB1, and PPM1D. In addition, we also found notable differences in the prevalence of ELF3, TP53, PMS2, and FAT4 between renal pelvis and ureter carcinomas. Moreover, 22.90% and 33.90% of UTUC and UCB patients, respectively, had at least one deleterious/likely deleterious alteration in DDR related genes/pathways. Subsequently, mutational signature analysis revealed that UC patients with mutational signature 22, irrespective of UTUC or UCB, consistently had the markedly higher level of tumor mutational burden (TMB), which was proved to be positively correlated with the objective complete/partial response rate in the IMvigor210 cohort. By comparison, Chinese and Western UTUC patients also differed regrading GAs in oncogenic-related genes/pathways, especially in TP53, RTK/RAS, and PI3K pathways; besides, more alterations in WNT pathway but less TP53, RTK/RAS, HIPPO, and PI3K pathways were identified in Chinese UCB. Discussions: The in-depth analysis of genomic mutational landscapes revealed distinct pathogenetic mechanisms between Chinese UTUC and UCB, and specific genomic characterizations could identify high risk population of UTUC/UCB and provided information regarding the selection of alternative therapeutic regimens.

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.

Comprehensive bioinformatics analyses of APOBECs family and identification of APOBEC3D as the unfavorable prognostic biomarker in clear cell renal cell carcinoma.

Purpose: At present, how early screening for ccRCC is still a thorny issue for urologists. Probing the mechanisms underlying the development of ccRCC and finding relevant prognostic biomarkers remains crucial. Therefore, we systematically analyzed the APOBEC family in this study and identified APOBEC3D as a prognostic biomarker. Methods: In this study, based on the TCGA database, we systematically assessed the expression and prognosis of the APOBEC family and analyzed potential bioinformatic pathways. We then constructed nomograms to predict the prognosis of ccRCC patients better. Afterward, we further focused on APOBEC3D in our data on ccRCC specimens. The APOBEC3D should be extensively studied in ccRCC in the future. Results: The results showed that the APOBEC family showed the most significant changes in expression in ccRCC. The pathway enrichment analysis showed that APOBEC3 family members mainly regulated cytidine and cytosine-related processes. Subsequently, the Cox regression was used to construct prognostic signature, and validated in ICGC and GEO databases. Next, a nomogram was created integrating clinical parameters showing good predictive performance. Finally, we screened for APOBEC3D and found in our clinical sample that patients with high expression of APOBEC3D had a worse prognosis. Conclusion: Based on these results, APOBEC family members play important roles in the development of ccRCC, and APOBEC3D could serve as the biomarker for predicting patient prognosis.

Robotic ureteral reimplantation for the management of ureterovaginal fistula: four cases at a single center.

BACKGROUND: To describe our initial experience with robotic ureteral reimplantation for the management of ureterovaginal fistulas. METHODS: Between January 2018 and January 2020, four patients received robotic ureteral reimplantation for ureterovaginal fistulas. All patients were diagnosed based on anterograde urography and computed tomography urography (CTU). Follow-up was performed with magnetic resonance urography and renal ultrasound as well as the clinical assessment of symptoms. RESULTS: The mean age of all patients was 50.3 (range, 37-65) years. The cause of the ureterovaginal fistula in four patients was due to a previous hysterectomy. The mean time from fistula diagnosis to robotic repair surgery was 14.5 (range, 3-36) months. All robotic procedures were successfully performed without intraoperative complications or open conversion. The mean operative time was 137 (range, 116-171) minutes, and the mean estimated blood loss was 25 (range, 10-50) mL. No postoperative complications that were high grade (grade III and IV) occurred within one month of surgery. Patients had the double-J (D-J) stents removed 2 months after surgery and the nephrostomy tubes removed 3 months after the operation. There was a 100% success rate without serious complications, such as the leakage of urine and side progressive hydronephrosis, during the 6 to 24 months of follow-up. CONCLUSIONS: Our initial results and experience showed that robotic ureteral reimplantation for the management of ureterovaginal fistula is safe and feasible.

Initial experiences with preoperative three-dimensional image reconstruction technology in laparoscopic pyeloplasty for ureteropelvic junction obstruction.

BACKGROUND: To explore the clinical value of three-dimensional image reconstruction technology (3DIT) on preoperative surgical planning and perioperative outcomes in laparoscopic pyeloplasty (LP). METHODS: Data of 25 patients with ureteropelvic junction obstruction (UPJO) admitted to our hospital from January 2018 to January 2019 was analyzed retrospectively. All patients underwent preoperative enhanced computed tomography (CT) scanning. In the 12 cases in the 3DIT group, preoperative planning involved the use of virtual operation and morphometry based on reconstruction of the CT data into three-dimensional (3D) images. Surgery in the other 13 cases was performed with traditional CT examination. Demographic, surgical outcome, and postoperative parameters were compared between these two groups. RESULTS: Reconstructed 3D images clearly showed the spatial structural relationships between the UPJO and surrounding blood vessels. In all 25 cases surgery was completed with no conversion to open surgery. Preoperative 3DIT analyses resulted in significant improvements to mean operation time (107.76 vs. 141.58 min, P=0.024), mean time of dissociating ureteropelvic junction (UPJ) (11.26 vs. 19.40 min, P=0.020), and mean estimated blood loss volume (23.84 vs. 49.16 mL, P=0.028). There were no statistically significant differences in perioperative complications, postoperative hospital stays or postoperative drainage time. CONCLUSIONS: 3DIT based on enhanced CT scans is of clinical value in the treatment of UPJO, as it can provide accurate anatomical information and reliable guidance for preoperative operation planning, and it facilitates image-guided LP.

Prognostic Value and Potential Biological Functions of CLDN8 in Patients with Clear Cell Renal Cell Carcinoma.

PURPOSE: Clear cell renal cell carcinoma (ccRCC) is among the most common malignant tumors worldwide, with a high incidence rate and poor prognosis. Currently, there are no biomarkers that can accurately guide prognostic evaluation and therapeutic strategy for ccRCC. The prognostic value and potential biological function of claudin-8 (CLDN8), a critical component of tight junctions in ccRCC, remain unclear. METHODS: Sequencing data were obtained from The Cancer Genome Atlas, International Cancer Genome Consortium, and Gene Expression Omnibus databases. R packages were used to explore CLDN8 mRNA expression levels and analyze differentially expressed genes. Results were validated in clinical specimens and cell lines, and bioinformatics analyses were conducted to explore the potential biological functions of CLDN8. Finally, functional analyses were carried out using 786-O ccRCC cell line. RESULTS: Both CLDN8 mRNA and protein expression levels were significantly lower in ccRCC compared with the normal control tissues. Kaplan-Meier analyses showed that low CLDN8 expression levels were associated with the poor overall survival, while univariate and multivariate Cox regression indicated that CLDN8 could serve as an independent prognostic factor in patient with ccRCC. Bioinformatic and Western blot analyses showed that CLDN8 suppressed proliferation, migration, and invasion of 786-O ccRCC cells through the epithelial-mesenchymal transition and AKT pathways. CONCLUSION: CLDN8 could serve as an independent prognostic factor in ccRCC, in which it suppresses 786-O proliferation, migration, and invasion through EMT and AKT pathways.