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Purpose: Fumarate hydratase–deficient renal cell carcinoma (FH-deficient RCC) is a rare but lethal subtype of RCC. Little is known about the genomic profile of FH-deficient RCC, and the therapeutic options for advanced disease are limited. To this end, we performed a comprehensive genomics study to characterize the genomic and epigenomic features of FH-deficient RCC. Experimental Design: Integrated genomic, epigenomic, and molecular analyses were performed on 25 untreated primary FH-deficient RCCs. Complete clinicopathologic and follow-up data of these patients were recorded. Results: We identified that FH-deficient RCC manifested low somatic mutation burden (median 0.58 mutations per megabase), but with frequent somatic copy-number alterations. The majority of FH-deficient RCCs were characterized by a CpG sites island methylator phenotype, displaying concerted hypermethylation at numerous CpG sites in genes of transcription factors, tumor suppressors, and tumor hallmark pathways. However, a few cases (20%) with low metastatic potential showed relatively low DNA methylation levels, indicating the heterogeneity of methylation pattern in FH-deficient RCC. Moreover, FH-deficient RCC is potentially highly immunogenic, characterized by increased tumor T-cell infiltration but high expression of immune checkpoint molecules in tumors. Clinical data further demonstrated that patients receiving immune checkpoint blockade–based treatment achieved improved progression-free survival over those treated with antiangiogenic monotherapy (median, 13.3 vs. 5.1 months; P = 0.03). Conclusions: These results reveal the genomic features and provide new insight into potential therapeutic strategies for FH-deficient RCC.

Benign prostatic hyperplasia (BPH) occurs most commonly among older men, often accompanied by chronic tissue inflammation. Although its aetiology remains unclear, autoimmune dysregulation may contribute to BPH. Regulatory T cells (Tregs) prevent autoimmune responses and maintain immune homeostasis. In this study, we aimed to investigate Tregs frequency, phenotype, and function in BPH patients and to evaluate adoptive transfer Tregs for immunotherapy in mice with BPH via CD39. Prostate specimens and peripheral blood from BPH patients were used to investigate Treg subsets, phenotype and Treg‐associated cytokine production. Sorted CD39+/− Tregs from healthy mice were adoptively transferred into mice before or after testosterone propionate administration. The Tregs percentage in peripheral blood from BPH patients was attenuated, exhibiting low Foxp3 and CD39 expression with low levels of serum IL‐10, IL‐35 and TGF‐β. Immunohistochemistry revealed Foxp3+ cells were significantly diminished in BPH prostate with severe inflammatory. Although the Tregs subset was comprised of more effector/memory Tregs, CD39 was still down‐regulated on effector/memory Tregs in BPH patients. Before or after testosterone propionate administration, no alterations of BPH symptoms were observed due to CD39‐ Tregs in mice, however, CD39+Tregs existed more potency than Tregs to regulate prostatic hyperplasia and inhibit inflammation by decreasing IL‐1β and PSA secretion, and increasing IL‐10 and TGF‐β secretion. Furthermore, adoptive transfer with functional Tregs not only improved prostate hyperplasia but also regulated muscle cell proliferation in bladder. Adoptive transfer with Tregs may provide a novel method for the prevention and treatment of BPH clinically.

The discovery of novel non-invasive biomarkers for discriminating between prostate carcinoma (PCa) patients and benign prostatic hyperplasia (BPH) patients is necessary to reduce the burden of biopsies, avoid overdiagnosis and improve quality of life. Previous studies suggest that abnormal glycosylation of immunoglobulin gamma molecules (IgGs) is strongly associated with immunological diseases and prostate diseases. Hence, characterizing N-linked intact glycopeptides of IgGs that correspond to the N-glycan structure with specific site information might enable a better understanding of the molecular pathogenesis and discovery of novel signatures in preoperative discrimination of BPH from PCa. In this study, we profiled N-linked intact glycopeptides of purified IgGs from 51 PCa patients and 45 BPH patients by our developed N-glycoproteomic method using hydrophilic interaction liquid chromatography enrichment coupled with high resolution LC-MS/MS. The quantitative analysis of the N-linked intact glycopeptides using pGlyco 2.0 and MaxQuant software provided quantitative information on plasma IgG subclass-specific and site-specific N-glycosylation. As a result, we found four aberrantly expressed N-linked intact glycopeptides across different IgG subclasses. In particular, the N-glycopeptide IgG2-GP09 (EEQFNSTFR (H5N5S1)) was dramatically elevated in plasma from PCa patients, compared with that in BPH patients (PCa/BPH ratio = 5.74, p = 0.001). Additionally, the variations in these N-linked intact glycopeptide abundances were not caused by the changes in the IgG concentrations. Furthermore, IgG2-GP09 displayed a more powerful prediction capability (auROC = 0.702) for distinguishing PCa from BPH than the clinical index t-PSA (auROC = 0.681) when used alone or in combination with other indicators (auROC = 0.853). In conclusion, these abnormally expressed N-linked intact glycopeptides have potential for non-invasive monitoring and pre-stratification of prostate diseases.

Objective: To compare these managements focusing on the efficacy and safety to treat overactive bladder (OAB) in children through network meta-analysis (NMA). Methods: We searched PubMed, Embase, the Cochrane Library Central Register of Controlled Trials (CENTRAL) and the reference lists up to May 1st, 2017. Data from eligible randomized controlled trails (RCT) studies including three different treatment options were extracted. The primary outcome was maximal voiding volume (MVV). We performed pairwise meta-analyses by random effects model and NMA by Bayesian model. We used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework to assess the quality of evidence contributing to each network estimate. Results: Six RCTs (462 patients) comparing three different interventions fulfilled the inclusion criteria. A low risk of bias was shown for the majority of the study items. The results of NMA showed that compared with antimuscarinic drugs, Parasacral transcutaneous electrical nerve stimulation was associated with significant improvement in the MVV (mean difference [MD] = 58.50, 95% confidential interval [CI]: 45.95–69.52), followed by urotherapy group (MD = 21.03, 95% CI: 11.85–29.97). When it comes to the constipation, antimuscarinic drugs exerted significant benefit than PTENS (odds ratio [OR]: 0.22, 95% CI: 0.01–0.46). No significant difference was found between other treatments. Conclusion: Compared with antimuscarinic drugs, PTENS was associated with significant better efficacy considering MVV, but more constipation events in de novo OAB children. Antimuscarinic drugs showed remarkably better efficacy considering MVV and comparable safety profile compared with urotherapy. Clinicians should take all known safety and compliance of patients into account when choosing an optimal strategy. Keywords: Overactive bladder, Meta-analysis, Anticholinergics, Parasacral transcutaneous electrical nerve stimulation

Objective: Administration of drugs targeting anti-cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) is often associated with serious immune-related adverse events (irAEs). Here, we performed a comprehensive analysis of organ-specific irAEs and treatment-related hematologic abnormalities and musculoskeletal disorders resulting from anti-CTLA-4 treatment. Materials and methods: PubMed, the Cochrane library, Web of Science, and ClinicalTrials.gov were searched for studies between January 1990 and March 2018 reporting AEs associated with anti-CTLA-4 therapies. Results: A total of 11 clinical trials with 7,088 patients were included; of these, data were accessible for 10 on ClinicalTrials.gov. Compared with control therapies (placebo, chemotherapy, radiation therapy, or vaccine), anti-CTLA-4 therapies (ipilimumab and tremelimumab) were associated with an increased risk of serious irAEs, predominantly dermatologic (rash: odds ratio [OR] 3.39, P

This study aimed to further validate the prognostic role of fibrinogen in upper tract urothelial carcinoma (UTUC) in a large Chinese cohort. A total of 703 patients who underwent radical nephroureterectomy were retrospectively identified. Fibrinogen levels of ≥4.025 g l-1 were defined as elevated. Logistic regression analysis was performed to determine the association between fibrinogen and adverse pathological features. Kaplan-Meier analysis and Cox regression models were used to assess the associations of fibrinogen with cancer-specific survival (CSS), disease recurrence-free survival (RFS), and overall survival (OS). Harrell c-index and decision curve analysis were used to assess the clinical utility of multivariate models. The median follow-up duration was 42 (range: 1-168) months. Logistic regression analysis revealed that elevated fibrinogen was associated with higher tumor stage and grade, lymph node involvement, lymphovascular invasion, sessile carcinoma, concomitant variant histology, and positive surgical margins (all P < 0.05). Multivariate Cox regression analysis demonstrated that elevated fibrinogen was independently associated with decreased CSS (hazard ratio [HR]: 2.33; P < 0.001), RFS (HR: 2.09; P < 0.001), and OS (HR: 2.09; P < 0.001). The predictive accuracies of the multivariate models were improved by 3.2%, 2.0%, and 2.8% for CSS, RFS, and OS, respectively, when fibrinogen was added. Decision curve analysis showed an added benefit for CSS prediction when fibrinogen was added to the model. Preoperative fibrinogen may be a strong independent predictor of worse oncologic outcomes in UTUC; therefore, it may be valuable to apply this marker to the current risk stratification in UTUC.

Background To investigate the expression of estrogen receptor (ER) in prostate tissues of benign prostatic hyperplasia (BPH) individuals, and the effects of estrogen regulating the proliferation and inflammatory expressions of primary prostate stromal cells in BPH. Methods A total of 44 human BPH prostate tissues were collected to explore the expression of ER by immunohistochemistry (IHC). Cell proliferation, mRNA and protein expressions were analyzed in primary prostate stromal cells treated with estrogen or estrogen plus fulvestrant through cell count kit-8 (CCK-8) assay, quantitative real-time polymerase chain reaction (qPCR), IHC and western blot, respectively. Results Firstly, ERβ was positive, and ERα was negative in the transition zone of prostate among all the 44 individuals with BPH. Secondly, the effects could be partially inhibited by fulvestrant, of estrogen promoting the proliferation of primary prostate stromal cells cultured in dulbecco's modified eagle medium (DMEM) supplemented with 2% fetal bovine serum (FBS). Thirdly, estrogen up-regulates the mRNA levels of C-C chemokine receptor type 3 (CCR3), CD40 ligand (CD 40L), C-X-C motif chemokine ligand 9 (CXCL9) and interleukin 10 (IL10), and down-regulates the mRNA levels of C-C chemokine receptor type 4 (CCR4) and interleukin 17C (IL17C). Then, the protein expressions of CCR3, CCR4, CD40L, IL10 and IL17C are positive, and CXCL9 is negative in the third-generation primary prostate stromal cells. Finally, the effects could be partially inhibited by fulvestrant, of estrogen up-regulating the protein levels of CD40L and IL10. Conclusions The expressions of ER in human BPH prostate tissues are zone-dependent. Estrogen promoting the proliferation of primary prostate stromal cells cultured in DMEM supplemented with 2% FBS. The expressions of CCR3, CCR4, CD 40L, IL17C, CXCL9 and IL10 are regulated by estrogen in primary prostate stromal cells.

Introduction Prebiopsy multiparametric magnetic resonance imaging (mpMRI) has been increasingly utilized for patients of suspicious prostate cancer (PCa). However, the optimal core number and site for MRI-targeted biopsy have not been clearly elucidated. Evidence acquisition A systematic search in Pubmed, Embase and Ovid up to June 2019 was conducted and we identified studies reporting detection details of every MRI-targeted core. The incremental diagnostic value of performing additional cores was pooled on per-lesion analysis. Our secondary outcome concentrated on detection accuracy for cores of different site within one lesion. Evidence synthesis Five studies comprising 2291 patients were identified to elucidate the association between targeted core number and cancer detection rates. Adding the second core to the first one resulted in 19.8% (range: 13.6-26.7%) increase in the detection rate of clinically significant lesions, and adding the third one to the first two resulted in 11.5% (range: 7.8-14.3%) increase. The incremental value of adding the fourth or the fifth core was 6.0% (4.7%, 6.9%) and 4.1% respectively. Four studies arranging MRI-targeted biopsy of more than two cores in well-determined sequences indicated more positive cores with higher cancer grade through center of the lesions. Conclusions Increasing the number of samples per target from one to two, or two to three resulted in a nonnegligible incremental detection rate of clinically significant lesions, while obtaining more than 3 cores per target provided a diminished incremental value. And performing targeted cores accurately through center of the lesions may help improve diagnostic accuracy.

BackgroundTo retrospectively investigate the clinical characteristics, initial treatment, relapse, therapy outcome, and prognosis of Chinese patients with primary testicular lymphoma (PTL) through analysis of the cases of our institute.MethodsFrom December 2008 to July 2018, all patients with PTL were included in this study. Kaplan-Meier method was used to estimate PFS and OS. The Cox proportional hazards model was used to compare the survival times for groups of patients differing in terms of clinical and laboratory parameters.ResultsAll 28 PTL patients (24 DLBCL, three NK/T lymphomas, and one Burkkit’s lymphoma) with a median age of 65.5 years were included in this study. Six patients were observed recurrence among all the 22 individuals evaluated. Following orchiectomy and systemic chemotherapy, with or without intrathecal prophylaxis, complete response was achieved in 15 (68%) patients. For DLBCL patients, the median progression-free survival (PFS) was 44.63 months (95% CI 17.71–71.56 months), and the median overall survival (OS) was 77.02 months (95% CI, 57.35–96.69 months). For all the DLBCL patients, the 5-year PFS and 5-year OS were 35.4% (95%CI, 14.8–56.0%) and 53.4% (95%CI, 30.1–76.7%). Without further chemotherapy following orchiectomy (HR = 3.4,P = 0.03) were associated with inferior PFS of DLBCL patients. Advanced Ann Arbor stage (HR =5.9,P = 0.009) and high (international prognostic index, IPI) score: 3–5 (HR =3.9,P = 0.04) were correlated with shorter OS of DLBCL patients.ConclusionThis study confirms that PTL is an aggressive malignant with a poor prognosis. Limited Ann Arbor stage, further chemotherapy following orchiectomy, and low IPI score (less than 2) are correlated with superior survival for DLBCL patients.

Introduction Our aim is to compare feasibility and safety of open radical cystectomy (ORC), laparoscopic radical cystectomy (LRC) and robot-assisted radical cystectomy (RARC) for the treatment of bladder cancer through network meta-analysis. Evidence acquisition Eligible articles were identified from electronic databases including PubMed/Medline, Embase, the Cochrane Library and Web of Science up to August 2019 with no language limitations. Studies selection, quality assessment, data extraction and analysis were accomplished by two independent reviewers (DCF and AL) using Cochrane Collaboration's tools. Evidence synthesis After screening 2528 articles, 27 studies were included in the final meta-analysis. In the network meta-analysis, both RARC (MD:83.09, 95% CI: 61.06 to 105.11) and LRC (MD: 49.68, 95% CI: 21.75 to 77.62) showed a longer operative time compared with ORC. Besides, RARC had a longer operative time than LRC (MD: 33.40, 95% CI: 1.35 to 65.45). RARC (MD:-591.86, 95% CI: -879.46 to -304.27) and LRC (MD: -435.28, 95% CI: -854.98 to -15.58) showed a less estimated blood loss (EBL) than ORC; however, the difference in EBL for RARC versus LRC was not significant. RARC (OR: 0.26, 95% CI: 0.14 to 0.50) and LRC (OR: 0.23, 95% CI: 0.13 to 0.43) had a higher blood transfusion rate than ORC; however, the OR between RARC and LRC was not significant. RARC (MD: -1.34, 95% CI: -2.55 to -0.12) and LRC (MD: -1.35, 95% CI: -2.38 to -0.32) took a shorter time to regular diet compared with ORC; however, there was no significant difference between RARC and LRC. Compared with ORC, RARC (MD: -2.37, 95% CI: -3.57 to -1.17) and LRC (MD: -2.22, 95% CI: -4.04 to -0.40) showed a shorter length of stay (LOS); however, the difference in LOS for RARC versus LRC was not significant. RARC, LRC and ORC were comparable with regard to minor complications, major complications, positive surgical margin and lymph node yields. Conclusions Current evidence indicates that minimally invasive approaches could be considered as a feasible and safe alternative to ORC when performed by experienced surgeons in selected patients. Notably, RARC may be more suitable for RC with extracorporeal urinary diversion. Larger well-designed trials are still needed to confirm these findings due to the observational nature of most studies.

Background Pretreatment controlling nutritional status (CONUT) score is a novel index which was used to predict outcomes in cancer patients. We aim to explore the prognostic significance of CONUT score in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). Patients and methods A total of 662 UTUC patients between 2004 and 2016 were retrospectively analyzed. Patients were categorized into three groups based on CONUT score (Normal: 0‐1; Light: 2‐4; Moderate/severe: 5‐12). Associations of CONUT score with oncological outcomes were analyzed using Logistic and Cox regression analysis. Harrell concordance index was used to assess the predictive accuracy of the multivariate models. Subgroup analyses were conducted according to tumor grade and stage. Results The median follow‐up duration was 41 months. Multivariate Logistic analysis showed that high CONUT score was independently associated with high‐grade disease, high pT stage, lymphovascular invasion, sessile carcinoma, variant histology, and positive surgical margins (each P

To identify the impact of albumin-globulin ratio (AGR) on pathologic and survival outcomes in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU).We retrospectively reviewed medical records of 620 patients treated with RNU for UTUC at our institution. Logistic regression analysis was used to evaluate the relation between low AGR (1.45) and adverse pathologic features. Kaplan-Meier curves were used to estimate recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) probabilities between 2 groups. Univariable and multivariable Cox regression models were performed to address prognostic factors related to RFS, CSS, and OS.Of the 620 patients, 323 (52.1%) had AGR 1.45. During a median follow-up of 50.0 months (interquartile range, 28-78 months), 277 (44.7%) experienced disease recurrence and 194 (31.3%) died of disease. The results showed that low AGR was significantly associated with adverse pathologic features (all P .05). Kaplan-Meier analysis showed that compared to those with high AGR (≥1.45), patients with low AGR had poorer RFS, CSS, and OS (P .001). After adjusting for the confounding clinicopathologic factors, multivariate analyses showed that AGR 1.45 independently predicted poor RFS (hazard ratio [HR] = 1.321, P = .029), CSS (HR = 1.503, P = .010) and OS (HR = 1.403, P = .015).Low preoperative AGR is an independent predictor of worse pathologic and oncologic outcomes in patients with UTUC after RNU. The application of AGR as an easily assessed blood-based biomarker in predicting the prognosis of patients with UTUC is promising.

Urothelial carcinoma (UC) is the most common type of cancer of the bladder and upper urinary tract, and is characterized by a high risk of recurrence and progression. Urine fluorescence in situ hybridization (FISH) is a technique that detects genetic aberrations in exfoliated cells in the urine, with specific probes for chromosomes 3, 7 and 17 and the p16 gene. To evaluate the diagnostic value of FISH in UC, 119 patients from November 2010 to June 2012 with suspected UC were recruited into a prospective, cross-sectional study and were followed up for 12-30 months. These patients received voided urine cytology and FISH tests, and underwent cystoscopy and/or ureteroscopy as a reference standard. The final diagnoses confirmed 73 patients with UC, located in the bladder, upper urinary tracts or the two. The sensitivity of FISH for detecting UC was superior to cytology, irrespective of tumor grade and stage: Overall, 80.8 vs. 32.9% (P

The tumor microenvironment is associated with various tumor progressions, including cancer metastasis, immunosuppression, and tumor sustained growth. Tumor‐associated macrophages (TAMs) are considered an indispensable component of the tumor microenvironment, participating in the progression of tumor microenvironment remodeling and creating various compounds to regulate tumor activities. This study aims to observe enriched TAMs in tumor tissues during bladder cancer development, which markedly facilitated the proliferation of bladder cancer cells and promoted tumor growth in vivo. We determined that TAMs regulate tumor sustained growth by secreting type I collagen, which can activate the prosurvival integrin α2β1/PI3K/AKT signaling pathway. Furthermore, traditional chemotherapeutic drugs combined with integrin α2β1 inhibitor showed intensive anticancer effects, revealing an innovative approach in clinical bladder cancer treatment.

INTRODUCTION Both oxidative stress and inflammation play important roles in prostate cancer cell apoptosis or proliferation; however, the mechanisms underlying these processes remain unclear. Thus, we selected interleukin-8 (IL-8) as the bridge between inflammation and cancer cell oxidative stress-induced death and aimed to confirm its connection with mTOR and Glycogen synthase kinase-3 beta (GSK-3β). METHODS We overexpressed GSK-3β and observed its effect on reactive oxygen species (ROS) and oxidative stress-induced cell death. IL-8 was then upregulated or downregulated to determine its impact on preventing cell damage due to GSK-3β-induced oxidative stress. In addition, we overexpressed or knocked down mTOR to confirm its role in this process. Real-time PCR, Western blotting, transcription, Cell Counting Kit 8 (CCK-8), and flow cytometry analyses were performed in addition to the use of other techniques. RESULTS IL-8 promotes prostate cancer cell proliferation and decreases apoptosis, whereas GSK-3β activates the caspase-3 signaling pathway by increasing ROS and thereby induces oxidative stress-mediated cell death. In addition, mTOR can also decrease activation of the caspase-3 signaling pathway by inhibiting GSK-3 and thus decreasing ROS production. Moreover, the inhibitory effect of IL-8 on GSK-3β occurs through the regulation of mTOR. CONCLUSION The results of this study highlight the importance of GSK-3β, which increases the production of ROS and thereby induces oxidative stress in tumor cells, whereas IL-8 and mTOR attenuate oxidative stress to protect prostate cancer cells through inhibition of GSK-3β.

The majority of clear cell renal cell carcinomas (ccRCCs) are caused by an accumulation of hypoxia-inducible factor (HIF) and the overexpression of downstream genes in response to the von Hippel-Lindau (VHL) gene becoming inactivated. In the present study, our hypothesis was that BNIP3, a gene positioned downstream of HIF, would be expressed at a higher level in ccRCC; however, instead, lower levels of BNIP3 expression were identified in RCC tumor tissues compared with adjacent non-tumor tissues. These changes were associated with lower levels of VHL, and higher levels of HIF and vascular endothelial growth factor. BNIP3 was also undetectable in three investigated RCC cell lines (786-O, ACHN, A498) and GRC-1-1 cells. Methylation of the BNIP3 promoter was not detected, and neither did treatment with a methylation inhibitor cause cell proliferation. However, treatment with a histone deacetylation inhibitor, trichostatin A (TSA), inhibited cultured RCC cell proliferation, promoted apoptosis and restored BNIP3 expression. Furthermore, histone deacetylation of the BNIP3 promoter was identified in ACHN and 786-O cells, and the acetylation status was restored following TSA treatment. Taken together, the results of the present study suggest that histone deacetylation, but not methylation, is most likely to cause BNIP3 inactivation in RCC. The data also indicated that restoration of BNIP3 expression by a histone deacetylation inhibitor led to growth inhibition and apoptotic promotion in RCC.

Background: To evaluate the effectiveness and safety of neoadjuvant chemotherapy (NAC) for locally advance prostate patients undergoing radical prostatectomy. Methods: PubMed/Medline, EMBASE, Web of Science, Ovid, Web of Knowledge, and Cochrane Library will be searched for studies related to the topic. The identification, inclusion and exclusion flow charts will be conducted according to PRISMA guidelines. The identified reports will be critically appraised using GRADE approach. Bias and heterogeneity of included studies will be assessed, and outcome measurements from individual studies will be combined with 95% confidence interval using a fixed- or random-effects model if qualified. Results: This study will provide evidence and data on the tolerance and efficacy of NAC followed by radical prostatectomy (RP). Conclusion: The application of taxanes-based chemotherapy has been widened to metastatic hormone sensitive prostate cancer in recent years. To be more vigorous, whether neoadjuvant administration of these cytotoxic agents can improve the outcome of RP in locally advance prostate cancer patients has been explored. This study aims to synthesis data regarding the adverse effect, response rate, recurrence, and survival from multiple trials, and to guide the healthcare practitioners using an evidence-based approach.

Metabolic syndrome (MetS) has been reported to be associated with adverse outcomes in cancer patients. However, the relationship between MetS and upper tract urothelial carcinoma (UTUC) has yet to be explored.To investigate the prognostic value of MetS in UTUC after radical nephroureterectomy.A total of 644 patients with UTUC after radical nephroureterectomy were identified at West China Hospital from May 2003 to December 2016. MetS was defined as the co-existence of 3 or more of 5 components (obesity, hypertension, elevated fasting glucose, decreased high-density lipoprotein-cholesterol, and hypertriglyceridemia). Logistic and Cox regression analyses were performed to evaluate the associations of MetS with pathological features and survival outcomes. Decision curve analysis and Harrell concordance index were used to determine the clinical utility of the prediction models.Of 644 patients, 157 (24.4%) had MetS. Over a median follow-up of 39 months, 269 (41.8%) experienced disease recurrence, 233 (36.2%) died, and 185 (28.7%) died of UTUC. MetS was independently associated with high-grade disease, advanced pT stage (≥pT3), and lymphovascular invasion (each P0.05). Multivariate Cox regression analysis showed that MetS was an independent factor for decreased cancer-specific survival (hazard ratio [HR]: 1.38, 95% confidence intervals [CI]: 1.01-1.89, P = 0.042) but not for recurrence-free survival (HR: 1.27, 95% CI: 0.97-1.67, P = 0.078), and overall survival (HR: 1.24, 95% CI: 0.95-1.62, P = 0.121). The estimated c-index of the multivariate models for cancer-specific survival was 0.763 compared with 0.769 when MetS added.MetS is a negative prognostic factor in UTUC. Further studies of MetS in UTUC are demanded.

Background:To evaluate the diagnostic effectiveness and predictive value of fluorescence in situ hybridization (FISH) in the surveillance of non-muscle invasive bladder cancer (NMIBC).Methods:PubMed/Medline, EMBASE, Web of Science, Ovid, Web of Knowledge, and Cochrane Library will be searche

Objective: To compare the relative effectiveness of fluorescence in situ hybridization (FISH) and cytology in diagnosing upper urinary tract urothelial carcinoma (UUT-UC) and to evaluate the advantages and potential deficiencies of FISH analysis. Methods: We performed a complete systematic review based on studies from PubMed/Medline, Embase, Web of Science, Ovid, Web of Knowledge, and Cochrane Library. We identified 2031 patients with strict criteria in 14 individual studies between January 2005 to November 2017 in accordance to preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines, we summarized the test performance using bivariate random effects models. Results: FISH was superior to cytology in terms of pooled sensitivities (84.0%, 95% confidence interval [CI] 74.4–90.5% vs 40.0%, 95% CI 33.6–46.7%). FISH and cytology were similar to each other in terms of pooled specificities, which were 89.5% (95% CI 85.3–92.6%) for FISH and 95.9% (95% CI 91.2–98.1%) for cytology. Conclusion: We confirm the superiority of FISH over cytology in terms of sensitivity and find similar diagnostic outcomes between them based on systematic analysis. Therefore, we demonstrate that FISH is extremely sensitive while still very reliable with a relatively low error rate for diagnosing UUT-UC.