Applications of CRISPR technology in cellular immunotherapy.

CRISPR technology has transformed multiple fields, including cancer and immunology. CRISPR-based gene editing and screening empowers direct genomic manipulation of immune cells, opening doors to unbiased functional genetic screens. These screens aid in the discovery of novel factors that regulate and reprogram immune responses, offering novel drug targets. The engineering of immune cells using CRISPR has sparked a transformation in the cellular immunotherapy field, resulting in a multitude of ongoing clinical trials. In this review, we discuss the development and applications of CRISPR and related gene editing technologies in immune cells, focusing on functional genomics screening, gene editing-based cell therapies, as well as future directions in this rapidly advancing field.

Thiazolidinedione enhances the efficacy of anti-PD-1 monoclonal antibody in murine melanoma.

Several clinical studies observed a surprising beneficial effect of obesity on enhancing immunotherapy responsiveness in patients with melanoma, highlighting an as-yet insufficiently understood relationship between metabolism and immunogenicity. Here, we demonstrate that the thiazolidinedione (TZD) rosiglitazone, a drug commonly used to treat diabetes by sequestering fatty acids in metabolically inert subcutaneous adipose tissue, improved sensitivity to anti-programmed cell death protein 1 (PD-1) treatment in YUMMER1.7 tumor-bearing mice, an initially immunotherapy-sensitive murine melanoma model. We observed a transition from high to intermediate PD-1 expression in tumor-infiltrating CD8+ T cells. Moreover, TZD inhibited PD-1 expression in mouse and human T cells treated in vitro. In addition to its direct impact on immune cells, TZD also decreased circulating insulin concentrations, while insulin induced T cell exhaustion in culture. In TZD-treated mice, we observed higher fatty acid concentrations in the tumor microenvironment, with fatty acids protecting against exhaustion in culture. Together, these data are consistent with an indirect mechanism of TZD inhibiting T cell exhaustion. Finally, we analyzed imaging data from patients with melanoma before and after anti-PD-1 treatment, confirming the beneficial effect of increased subcutaneous fat on anti-PD-1 responsiveness in patients. We also found that the expression of peroxisome proliferator-activated receptor gamma (PPARγ), the canonical activator of lipid uptake and adipogenesis activated by TZD, correlated with overall survival time. Taken together, these data identify a new adjuvant to enhance immunotherapy efficacy in YUMMER1.7 melanoma mice, and discover a new metabolism-based prognostic marker in human melanoma.NEW & NOTEWORTHY Zhang et al. demonstrate that the diabetes drug rosiglitazone improves the efficacy of immunotherapy in mouse melanoma. This effect is both direct and indirect: TZD directly reduces PD-1 expression in CD8+ T cells (i.e., reduces exhaustion), and indirectly reduces exhaustion by lowering insulin levels and increasing local fat. Finally, they demonstrate that hallmarks of TZD action (such as PPARγ expression and subcutaneous fat content) correlate with improved immunotherapy efficacy in humans with melanoma.

Modified Ileal Conduit for Pelvic Lipomatosis: Technique Description and Outcome.

INTRODUCTION: To present the surgical technique and clinical outcomes of modified ileal conduit for pelvic lipomatosis (PL). METHODS: From 2020 to 2022, we prospectively enrolled 9 patients with PL undergoing modified ileal conduit. The patient characteristics, perioperative variables, and follow-up outcomes as well as the description of surgical technique were reported. RESULTS: All 9 patients successfully completed the operation. Two patients had perioperative complications of Clavien-Dindo grade I. The mean operation time and bleeding volumes were 253±51.4 min and 238.9±196.9 ml, with a mean postoperative follow-up time of 13.0±5.6 months. The postoperative 3-month and 1-year creatinine values were significantly decreased versus the preoperative (P=0.006 and P=0.024). The postoperative 3-month and 1-year eGFR values were significantly increased comapred with those before operation (P=0.0002 and P=0.018). The separation value of left renal pelvis collection system after operation were significantly reduced compared with preoperative evaluation (P=0.023 at 3 month and P=0.042 at 1 year) and so was the right side (P=0.019 and P=0.023). CONCLUSION: Modified ileal conduit is safe and feasible for PL. A large sample cohort with long-term follow-up is needed to evaluate the clinical outcomes of PL.

The DDD score outperforms the RENAL score in predicting high-grade renal cell carcinoma.

OBJECTIVES: To explore the relationship between Fuhrman grade of renal cell carcinoma (RCC) and the DDD score. METHODS: We reviewed the records of 527 nonmetastatic RCC patients. Demographic, clinical, and pathologic characteristics were reviewed. Binary logistic regression was used to explore the independent risk factors for high-grade RCC (HGRCC). RESULTS: Sex, BMI (Body Mass Index), RNS, and DDD score were significantly correlated with HGRCC. Based on these independent risk factors, we constructed two predictive models integrating the RNS and DDD scores with sex and BMI to predict tumor grade. The calibration curves of the predictive model showed good agreement between the observations and predictions. The concordance indexes (C-indexes) of the predictive models were 0.768 (95% CI, 0.713-0.824), and 0.809 (95% CI, 0.759-0.859). Receiver operating characteristic (ROC) curves were performed to compare the predictive power of the nomograms, and the prediction model including the DDD score had better prognostic ability (p = 0.01). CONCLUSIONS: This study found that RNS, DDD score, BMI, and sex were independent predictors of HGRCC. We developed effective nomograms integrating the above risk factors to predict HGRCC. Of note, the nomogram including the DDD score achieves better prediction ability for HGRCC.

Minimally invasive ureteroplasty with lingual mucosal graft for complex ureteral stricture: analysis of surgical and patient-reported outcomes.

OBJECTIVE: To evaluate objective treatment efficacy and safety, and subjective patient-reported outcomes in patients with complex ureteral strictures (US) undergoing minimally invasive lingual mucosal graft ureteroplasty (LMGU). MATERIALS AND METHODS: We prospectively enrolled patients underwent robotic or laparoscopic LMGU between May 2020 and July 2022. Clinical success was defined as symptom-free and no radiographic evidence of re-obstruction. Patient-reported outcomes, including health-related quality of life (HRQoL), mental health status and oral health-related quality of life (OHRQoL), were longitudinally evaluated before surgery, 6 and 12 months postoperatively. RESULTS: Overall, 41 consecutive patients were included. All procedures were performed successfully with 32 patients in robotic approach and 9 in laparoscopic. Forty (97.56%) patients achieved clinical success during the median follow-up of 29 (range 15-41) months. Although patients with complex US experienced poor baseline HRQoL, there was a remarkable improvement following LMGU. Specifically, the 6-month and 12-month postoperative scores were significantly improved compared to the baseline (p < 0.05) in most domains. Twenty-eight (68.3%) and 31 (75.6%) patients had anxiety and depression symptoms before surgery, respectively. However, no significant decrease in the incidence of these symptoms was observed postoperatively. Moreover, there was no significant deterioration of OHRQoL at 6 months and 12 months postoperatively when compared to the baseline. CONCLUSIONS: LMGU is a safe and efficient procedure for complex ureteral reconstruction that significantly improves patient-reported HRQoL without compromising OHRQoL. Assessing patients' quality of life enables us to monitor postoperative recovery and progress, which should be considered as one of the criteria for surgical success.

The tumour-associated stroma correlates with poor clinical outcomes and immunoevasive contexture in patients with upper tract urothelial carcinoma: results from a multicenter real-world study (TSU-01 Study).

BACKGROUND: In this real-world study, we aimed to elucidate the predictive value of tumour-associated stroma for clinical prognostic and therapeutic response in upper tract urothelial carcinoma (UTUC) by reviewing the clinicopathologic characteristics of 1015 UTUC patients through a nationwide multicenter analysis. METHODS: The tumour-stroma ratio (TSR) was assessed based on tissue sections stained for hematoxylin and eosin (H&E), and patients were further stratified into stroma-high (>50% stroma) and stroma-low group (≤50% stroma). Kaplan-Meier curve and Cox regression hazard analysis were conducted to assess the survival outcomes of UTUC patients. Bioinformatics analysis and immunostaining analysis were applied to portray the tumour microenvironment (TME). RESULTS: Stroma-high UTUC was significantly associated with poorer survival outcomes and inferior chemotherapeutic responsiveness. Our established nomogram achieved a high prognostic accuracy in predicting overall survival and cancer-specific survival in both of the discovery cohort (area under the curve [AUC] 0.663 and 0.712) and the validation cohort (AUC 0.741 and 0.747). Moreover, stroma-high UTUC was correlated with immunoevasive TME accompanied by increased cancer-associated fibroblasts, tumour-associated macrophages and, conspicuously a cluster of highly exhausted CD8+ T cells. CONCLUSION: Our results showed stroma-high UTUC was associated with an inferior prognosis and an immunoevasive TME with exhausted CD8+ T cells in UTUC patients. Our TSR-based nomogram could be used to refine prognosis and inform treatment decisions of patients with UTUC.

Health-related quality of life (HRQoL), anxiety and depression in patients with ureteral stricture: a multi-institutional study.

PURPOSE: To evaluate health-related quality of life (HRQoL), anxiety and depression levels in patients with ureteral stricture (US) and to further investigate factors independently affecting this. METHODS: We prospectively recruited a cohort of 275 consecutive patients with US between June 2020 and April 2021. The participants were required to provide complete sociodemographic, clinical and pathologic information. All patients were administered questionnaires to evaluate HRQoL, anxiety and depression. Multivariate linear regression analyses were performed to assess the contribution of covariates on HRQoL, anxiety and depression. RESULTS: Patients with US, particularly iatrogenic US, scored significantly lower than the Chinese general population in all domains of the SF-36 (all p < 0.001), except SF. Increased age, female and high education attainment were independently associated with poor HRQoL. Interestingly, iatrogenic US, nephrostomy tube placement, urinary symptoms, high anxiety and depression level independently predicted poor HRQoL. Furthermore, the percentages of anxiety and depression cases in patients with US were 31.3% and 20.7%, respectively. Iatrogenic US and urinary symptoms, specifically waist discomfort, were the strongest predictors of increased levels of anxiety and depression. CONCLUSION: Patients with US exhibited poor quality of life and emotional status. Various factors independently predicted worse HRQoL and emotion, which provide potential targets for medical, lifestyle-related, psychological interventions.

Comparison of minimally invasive versus open pelvic organ-preserving radical cystectomy in female patients with bladder cancer: a multicenter propensity score matching analysis.

PURPOSE: To compare the perioperative and oncologic outcomes between minimally invasive pelvic organ-preserving radical cystectomy (MIPOPRC) and open pelvic organ-preserving radical cystectomy (open POPRC) among female patients with bladder cancer (BCa). METHODS: We identified female patients who underwent POPRC for BCa at three centers between January 2006 and April 2018. Female patients who underwent open POPRC were matched with those who underwent MIPOPRC using 1:1 propensity score (PS) matching. The patient demographics and perioperative and oncologic outcomes were evaluated for the comparison between MIPOPRC and open POPRC. RESULTS: Among the 158 patients enrolled, 83 patients underwent MIPOPRC, and 75 underwent open POPRC. A total of 60 MIPOPRC and 60 open POPRC patients were matched successfully. The cancer-specific survival (CSS) and recurrence-free survival (RFS) did not differ significantly in the propensity score-weighted cohort (p = 0.297 and p = 0.600, respectively). Subgroup analysis by age and pathologic stage in the matched cohort revealed that CSS and RFS were with no differences among all subgroups. Moreover, multivariable Cox regression analyses showed that the surgical approach (MIPOPRC vs open POPRC) was not a predictor of CSS (p = 0.250). CONCLUSION: MIPOPRC was non-inferior to open POPRC in terms of oncologic outcomes among female patients. MIPOPRC could be technically feasible in selected female patients with BCa.

A three-dimensional renal tumor anatomy and intrarenal relationship nephrometry (ADDD) for robot-assisted partial nephrectomy : 3D-CT based nephrometry for RAPN.

OBJECTIVE: To develop a 3D scoring system of tumor anatomy and intrarenal relationship for assessing surgical complexity and outcomes of robot-assisted partial nephrectomy (RAPN). METHODS: We prospectively enrolled patients with a renal tumor who had a 3D model and underwent RAPN between Mar 2019 and Mar 2022. The ADDD nephrometry consisted of the contact surface area between tumor and parenchyma (A), the depth of tumor invasion into the renal parenchyma (D1), the distance from tumor to the main intrarenal artery (D2), and to the collecting system (D3). The primary outcomes included perioperative complication rate and trifecta outcome (WIT ≤ 25 min, negative surgical margins, and no major complications). RESULTS: We enrolled a total of 301 patients. The mean tumor size was 2.93 ± 1.44 cm. There were 104 (34.6%) patients, 119 (39.5%) patients, and 78 (25.9%) patients in the low-, intermediate-, and high-risk groups, respectively. Each point increase in the ADDD score increased the risk of complications [hazard ratio (HR) 1.501]. A lower grade indicated a lower risk of failed trifecta (HR low group 15.103, intermediate group 9.258) and renal function damage (HR low risk 8.320, intermediate risk 3.165) compared to the high-risk group. The AUC of ADDD score and grade were 0.738 and 0.645 for predicting major complications, 0.766 and 0.714 for predicting trifecta outcome, and 0.746 and 0.730 for predicting postoperative renal function reservation. CONCLUSION: The 3D-ADDD scoring system shows the tumor anatomy and its intraparenchymal relationships and has better efficacy in predicting surgical outcomes of RAPN.

Robotic ureteral reconstruction for benign ureteral strictures: a systematic review of surgical techniques, complications and outcomes : Robotic Ureteral Reconstruction for Ureteral Strictures.

INTRODUCTION: Robotic ureteral reconstruction (RUR) has been widely used to treat ureteral diseases. To summarize the surgical techniques, complications, and outcomes following RUR, as well as to compare data on RUR with open and laparoscopic ureteral reconstruction. METHODS: Our systematic review was registered on the PROSPERO (CRD42022309364) database. The PubMed, Cochrane and Embase databases were searched for publications in English on 06-Feb-2022. Randomised-controlled trials (RCTs) or non-randomised cohort studies with sample size ≥ 10 cases were included. RESULTS: A total of 23 studies were included involving 996 patients and 1004 ureters from 13 non-comparative, and 10 retrospective comparative studies. No RCT study of RUR was reported. The success rate was reported ≥ 90% in 15 studies. Four studies reported 85-90% success rate. Meta-analyses for comparative studies showed that RUR had significantly lower estimated blood loss (EBL) (P = 0.006) and shorter length of stay (LOS) (P < 0.001) than the open approach. RUR had shorter operative time than laparoscopic surgery (P < 0.001). CONCLUSIONS: RUR is associated with lower EBL and shorter LOS than the open approach, and shorter operative time than the laparoscopic approach for the treatment of benign ureteral strictures. However, further studies and more evidence are needed to determine whether RUR is more superior.

NFE2L3 promotes tumor progression and predicts a poor prognosis of bladder cancer.

The high incidence and vulnerability to recurrence of bladder cancer (BLCA) is a challenge in the clinical. Recent studies have revealed that NFE2L3 plays a vital role in the carcinogenesis and progression of different human tumors. However, the role of NFE2L3 in BLCA has not been elucidated. In this study, NFE2L3 expression was significantly increased in BLCA samples. Its high expression was associated with advanced clinicopathological characteristics and was an independent prognostic factor for overall survival and metastasis-free survival in 106 patients with BLCA. In vitro and in vivo experiments demonstrated that NFE2L3 knockdown inhibited BLCA cells proliferation by inducing the cell cycle arrest and cell apoptosis. Meanwhile, NFE2L3 overexpression promotes BLCA cell migration and invasion in vitro cell lines and in vivo xenografts. Moreover, we identified many genes and pathway alterations associated with tumor progression and metastasis by performing RNA-Seq analysis and functional enrichment of NFE2L3 overexpressing BLCA cells. Mechanistic investigation reveals that overexpression of NFE2L3 promoted epithelial-mesenchymal transition in BLCA cells with decreased expression of gap junction-associated protein ZO-1 and epithelial marker E-cadherin with the elevation of transcription factors Snail1 and Snail2. Finally, we performed a comprehensive proteomics analysis to explore more potential molecular mechanisms. Our findings revealed that NFE2L3 might serve as a valuable clinical prognostic biomarker and therapeutic target in BLCA.

Identification of an IDO1-based immune classifier for survival prediction of upper tract urothelial carcinoma.

The limited response rate of immunotherapy in upper tract urothelial carcinoma (UTUC) might be attributed to additional immunosuppressive mechanisms in vivo. As a promising immune checkpoint target, the expression and prognostic role of indoleamine 2,3-dioxygenase 1 (IDO1) in UTUC remains unknown. In this study, the expression and prognostic value of IDO1 was analyzed in 251 patients from 3 independent cohorts. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to construct an IDO1-based immune classifier and external validation was performed to further validate the classifier. RNA sequencing and immunofluorescence were used to explore the immune contexture of different risk groups stratified by classifier. We found that high IDO1 expression on tumor cells (TC) indicated a poorer overall survival and disease-free survival in all cohorts. Patients with high expression of IDO1 TC possessed increased infiltration of CD4+ , CD8+ and Foxp3+ T cells. An immune classifier based on intratumoral CD8+ lymphocytes, IDO1 TC, and stromal PD-L1 expression status was developed, with its area under the curves (AUCs) values for overall survival at 5 y being 0.79 (95% confidence interval [CI] 0.65-0.93) in the discovery cohort, 0.75 (95% CI 0.58-0.92) and 0.78 (95% CI 0.65-0.92) in the internal and external validation cohorts, respectively. The high-risk group stratified by the immune classifier was associated with immunosuppressive contexture, accompanied by enhanced CD8+ T cells exhaustion patterns. Our IDO1-based immune classifier can provide a superior accuracy for survival prediction and lead to individual stratification of UTUC immune subtypes.

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.

Robot-Assisted Radical Prostatectomy Using the KangDuo Surgical Robot-01 System: A Prospective, Single-Center, Single-Arm Clinical Study.

PURPOSE: Our goal was to evaluate the feasibility, safety and effectiveness of the KangDuo Surgical Robot-01 (KD-SR-01) system for robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: This prospective, single-center, single-arm clinical study was conducted from May 2021 to August 2021. Sixteen RARP procedures with the KD-SR-01 system were performed by 1 surgeon. The perioperative and followup data were prospectively recorded. Early oncologic outcomes were assessed according to surgical margin status and continence was defined as no more than 1 pad daily or urine leakage of ≤20 gm by the 24-hour pad weight test. Ergonomics were assessed with the NASA-TLX (National Aeronautics and Space Administration Task Load Index). RESULTS: All cases were completed successfully without conversion to traditional RARP, laparoscopic surgery or open surgery. The median docking time, console time and urethrovesical anastomosis time were 5.9 (range, 2.5-11.5), 87 (range, 70-120) and 14.4 minutes (range, 12.0-25.7), respectively. The median estimated blood loss was 50 ml (range, 10-200). None of patients required intraoperative transfusion. The median postoperative hospital stay was 5 days (range, 4-10). Overall, a positive surgical margin occurred in 4 (25%) patients. No biochemical recurrence occurred within 1 month after surgery. The continence rate was 87.5% (14/16) at 1 month after catheter removal. No severe intraoperative or postoperative complications (Clavien-Dindo grade ≥3) occurred. The surgeon reported a high comfort level with a NASA-TLX global score of 22.7±3.2. CONCLUSIONS: The KD-SR-01 system is feasible, safe and effective for management of localized prostate cancer.

Construction and validation of a ferroptosis-related long noncoding RNA signature in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is characterized by the accumulation of lipid-reactive oxygen species. Ferroptosis, due to the lipid peroxidation, has been reported to be strongly correlated with tumorigenesis and progression. However, the functions of the ferroptosis process in ccRCC remain unclear. METHODS: After sample cleaning, data integration, and batch effect removal, we used the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases to screen out the expression and prognostic value of ferroptosis-related lncRNAs and then performed the molecular subtyping using the K-means method. Then, the functional pathway enrichment and immune microenvironment infiltration between the different clusters were carried out. The results showed a significant difference in immune cell infiltration between the two clusters and the associated marker responded to individualized differences in treatment. Then, least absolute shrinkage and selection operator (LASSO) Cox regression was used to establish a prognostic signature based on 5 lncRNAs. This signature could accurately predicted patient prognosis and served as an independent clinical risk factor. We then combined significant clinical parameters in multivariate Cox regression and the prognostic signature to construct a clinical predictive nomogram, which provides appropriate guidance for predicting the overall survival of ccRCC patients. RESULTS: The prognostic differentially expressed ferroptosis-related LncRNAs (DEFRlncRNAs) were found, and 5 lncRNAs were finally used to establish the prognostic signature in the TCGA cohort, with subsequently validation in the internal and external cohorts. Moreover, we conducted the molecular subtyping and divided the patients in the TCGA cohort into two clusters showing differences in Hallmark pathways, immune infiltration, immune target expression, and drug therapies. Differences between clusters contributed to individualizing treatment. Furthermore, a nomogram was established to better predict the clinical outcomes of the ccRCC patients. CONCLUSIONS: Our study conducted molecular subtyping and established a novel predictive signature based on the ferroptosis-related lncRNAs, which contributed to the prognostic prediction and individualizing treatment of ccRCC patients.

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.

Ileal ureteral replacement for the management of ureteral avulsion during ureteroscopic lithotripsy: a case series.

INTRODUCTION: To describe our initial experience with ileal ureteral replacement (IUR) for the management of ureteral avulsion (UA) during ureteroscopic lithotripsy. METHODS: Between September 2010 and April 2021, ten patients received ileal ureteral replacement for ureteral avulsion during ureteroscopic lithotripsy. Anterograde urography and computed tomography urography (CTU) were applied to evaluate the lesion. Follow-up was performed with magnetic resonance urography and renal ultrasound as well as clinical assessment of symptoms. We retrospectively analysed the clinical data of ten patients treated with ileal ureteral replacement for the treatment of ureteral avulsion. RESULTS: Four patients underwent open ileal ureteral replacement, two underwent laparoscopic ileal ureteral replacement, and four underwent robotic-assisted ileal ureteral replacement. The mean operative time (OT) was 310 min (range 191-530). The mean estimated blood loss (EBL) was 193 mL (range 10-1000). The mean length of the ileal graft was 21 cm (range 12-25). The median postoperative hospital time was 13 days (range 7-19). All surgeries were effectively completed, and no case required open conversion in laparoscopic and robotic-assisted surgeries. There was no obvious hydronephrosis according to contrast-enhanced computed tomography 3-dimensional reconstruction images without serious complications or progressive hydronephrosis during a median follow-up duration of 51 months (range 5-131), and the success rate was 100%. CONCLUSIONS: Our initial results and experience showed that ileal ureteral replacement for the management of ureteral avulsion during ureteroscopic lithotripsy is safe and feasible.

Robot-assisted laparoscopic ileal ureter replacement with extracorporeal ileal segment preparation for long ureteral strictures: a case series.

BACKGROUND: Complete intracorporal robotic ileal ureteric replacement is challenging. We aimed to present the surgical technique of robotic ileal ureter replacement with extracorporeal ileal segment preparation for long ureteral strictures. METHODS: From March 2019 to March 2021, 18 patients underwent robotic ileal ureter replacement with extracorporeal ileal segment preparation by one experienced surgeon. The demographic, perioperative, and follow-up data were recorded. Success was defined as the resolution of the presenting symptom, a stable estimated glomerular filtration rate and unobstructive drainage on imaging examination. RESULTS: All 18 surgeries were successfully completed without conversion. The median length of the intestinal tube used was 20 (12-30) cm. The median operative time was 248 (170-450) min, the median estimated blood loss was 50 (10-200) ml, and the median postoperative hospital stay was 7 (5-27) days. At a median follow-up of 16 (13-28) months, all patients were symptom-free. No or mild hydronephrosis was confirmed in 17 patients; 1 patient had moderate hydronephrosis without peristalsis of the ileal ureter. The renal function was stable in all patients. The overall success rate was 100%. Postoperative complications, including 4 cases of urinary infections (Grade I), 1 case of an incision hernia (Grade I), 4 cases of kidney stone formation (Grade I), 6 cases of metabolic acidosis (Grade I), 4 cases of incomplete ileus (Grade II), and 1 case of an incision infection (Grade IIIb). CONCLUSIONS: Robot-assisted laparoscopic ileal ureter replacement with extracorporeal ileal segment preparation is safe, feasible, and effective for the treatment of long ureteral strictures, especially in high-volume tertiary referral centers with extensive robotic surgery experience capable of managing severe peri-operative complications.

Clinical Application of the Computed-Tomography-Based Three-Dimensional Models in the Surgical Planning and Intraoperative Navigation of Ureteropelvic Junction Obstruction Complicated with Renal Calculi.

Background and Objectives: To clinically validate the computed tomography (CT)-based three-dimension (3D) model for treatment planning and intraoperative navigation of ureteropelvic junction obstruction (UPJO) complicated with renal calculi. Materials and Methods: We retrospectively collected the data of 26 patients with UPJO and renal calculi who were surgically treated in our institution from January 2019 to December 2021. Before surgery, 3D models based on preoperative CT scans were constructed in all patients. Additionally, the patients were divided into three groups according to the results of 3D models, distinguished by different treatment of renal calculi, that is, left untreated (1), pyelolithotomy (2), and endoscopic lithotomy (3). The quantitative analysis of renal calculi parameters, and perioperative and follow-up data were compared. Results: The mean number of involved renal calyces (p = 0.041), and the mean maximum cross-sectional area (p = 0.036) of renal stones were statistically different among the three groups. There were no significant differences among the three groups in the mean operative time, mean estimated blood loss, mean pararenal draining time, and mean hospital stay. The intraoperative stone clearance rates were 100% (11/11) and 77.8% (7/9) in group 2 and group 3, respectively. The trends of increased estimated glomerular filtration rate and decreased creatinine on the average levels after surgery were observed, although these changes were not statistically significant. At a mean follow-up of 19.4 ± 6.4 months, the overall surgical success rate of the UPJO was 96.2% (25/26), and the overall success rate of renal calculi removal was 80.8% (21/26). Renal stones in 66.7% (4/6) of patients in group 1 spontaneously passed out. Conclusions: Preoperative 3D CT models have exact clinical value in the surgical planning and intraoperative navigation of UPJO patients complicated with renal calculi.

Let-7d inhibits intratumoral macrophage M2 polarization and subsequent tumor angiogenesis by targeting IL-13 and IL-10.

The microRNA let-7d has been reported to be a tumor suppressor in renal cell carcinoma (RCC). Tumor-associated macrophages (TAM) are M2-polarized macrophages that can enhance tumor growth and angiogenesis in many human cancers. However, the role of let-7d in TAM-associated RCC progression remains elusive. First, we observed a strongly inverse correlation between let-7d expression and microvessel density in RCC tissues. Furthermore, the proliferation, migration, and tube formation of HUVECs were significantly inhibited by conditioned medium from a coculture system of the phorbol myristate acetate pretreated human THP-1 macrophages and let-7d-overexpressing RCC cells. Moreover, the proportion of M2 macrophages was significantly lower in the group that was cocultured with let-7d-overexpressing RCC cells. Subcutaneous xenografts formed by the injection of let-7d-overexpressing RCC cells together with THP-1 cells resulted in a significant decrease in the M2 macrophage ratio and microvessel density compared with those formed by the injection of control RCC cells with THP-1 cells. In silico and experimental analysis revealed interleukin-10 (IL-10) and IL-13 as let-7d target genes. Importantly, the addition of IL-10 and IL-13 counteracted the inhibitory effects of the conditioned medium from the coculture system with let-7d-overexpressing RCC cells in vitro. Additionally, overexpression of IL-10 and IL-13 reversed the effects of let-7d on macrophage M2 polarization and tumor angiogenesis in vivo. Finally, the expression of IL-10 and IL-13 were inversely correlated with the expression of let-7d in RCC clinical specimens. These results suggest that let-7d may inhibit intratumoral macrophage M2 polarization and subsequent tumor angiogenesis by targeting IL-10 and IL-13.