Efficacy and safety evaluation of androgen deprivation therapy-based combinations for metastatic castration-sensitive prostate cancer: a systematic review and network meta-analysis.

BACKGROUND: This systematic review and network meta-analysis aimed to assess the comparative effectiveness and safety profiles of current combination therapies based on androgen deprivation therapy (ADT) for the heterogeneous population of individuals with metastatic castration-sensitive prostate cancer (mCSPC). METHODS: We retrieved pertinent literature from PubMed, EMBASE, the Cochrane Library, ClinicalTrials.gov, and international conference databases. The study was registered in the Prospective Register of Systematic Reviews (CRD42023453853) for transparency. RESULTS: Our analysis included 20 RCTs involving 14,995 patients, evaluating 15 ADT-based combinations, including systemic therapies, radiotherapy and surgery. In the overall population, the darolutamide triplet (DARO + docetaxel + ADT) demonstrated comparable overall survival (OS) benefits to prostatectomy/radical local therapy (RLT) plus ADT (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.43-1.57). Additionally, the enzalutamide (ENZ) triplet (ENZ + DOC + ADT) appeared to confer the best progression-free survival (HR, 0.34; 95% CI: 0.27-0.43). Subgroup analysis based on metastatic burden indicated that RLT plus ADT had the best OS performance in patients with low burden, while the DARO triplet was associated with the best OS in patients with high burden. Regarding adverse events (AEs), the addition of certain androgen receptor pathway inhibitor (ARPI) agents to ADT led to an increased incidence of severe AEs, while the addition of DOC to the ARPI doublet did not appear to elevate the exposure-adjusted incidence rates. CONCLUSIONS: Our findings suggest that combined treatments result in better survival outcomes than does ADT alone. In the current landscape of systemic therapy, the significance of local therapy should not be underestimated, and therapeutic decisions should be tailored with meticulous consideration of clinical heterogeneity among patients.

Comprehensive pan-cancer analysis of ZNF337 as a potential diagnostic, immunological, and prognostic biomarker.

BACKGROUND: Zinc Finger Protein 337 (ZNF337) is a novel Zinc Finger (ZNF) protein family member. However, the roles of ZNF337 in human cancers have not yet been investigated. METHODS: In this study, with the aid of TCGA databases, GTEx databases, and online websites, we determined the expression levels of ZNF337 in pan-cancer and its potential value as a diagnostic and prognostic marker for pan-cancer and analyzed the relationship between ZNF337 expression and immune cell infiltration and immune checkpoint genes. We then focused our research on the potential of ZNF337 as a biomarker for diagnostic and prognostic in KIRC (kidney renal clear cell carcinoma) and validated in the E-MTAB-1980 database. Moreover, the expression of ZNF337 was detected through qRT-PCR and Western blotting (WB). CCK-8 experiment, colony formation experiment, and EDU experiment were performed to evaluate cell proliferation ability. Wound healing assay and transwell assay were used to analyze its migration ability. The qRT-PCR and WB were used to detect the expression of ZNF337 in tumor tissues and paracancerous tissues of KIRC patients. RESULTS: The pan-cancer analysis revealed that abnormal ZNF337 expression was found in multiple human cancer types. ZNF337 had a high diagnostic value in pan-cancer and a significant association with the prognosis of certain cancers, indicating that ZNF337 may be a valuable prognostic biomarker for multiple cancers. Further analysis demonstrated that the expression level of ZNF337 displayed significant correlations with cancer-associated fibroblasts, immune cell infiltration, and immune checkpoint genes in many tumors. Additionally, ZNF337 was observed to have a high expression in KIRC. Its expression was significantly associated with poor prognosis [overall survival (OS), disease-specific survival (DSS)], age, TNM stage, histologic grade, and pathologic stage. The high ZNF337 expression was associated with poor prognosis in the E-MTAB-1980 validation cohort. The in vitro experiments suggested that the expression of ZNF337 in KIRC tumor tissues was higher than in adjacent tissues, and ZNF337 knockdown inhibited the proliferation and migration of KIRC cells, whereas overexpression of ZNF337 had the opposite effects. CONCLUSIONS: ZNF337 might be an important prognostic and immunotherapeutic biomarker for pan-cancer, especially in KIRC.

The efficacy of platelet rich plasma in the treatment of erectile dysfunction: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Erectile dysfunction (ED) is a common issue among males, and the use of platelet-rich plasma (PRP) therapy for treating ED has gained increasing attention, but there is still no conclusive evidence regarding its efficacy. AIM: To evaluate the efficacy of PRP therapy for ED. METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Web of Science databases up to November 2023 to identify randomized controlled trials (RCTs) on PRP therapy for ED. We used Review Manager version 5.4 for data analysis and management. RESULT: After applying inclusion and exclusion criteria for screening, a total of 4 studies involving 413 patients were finally included in our meta-analysis. According to our analysis, the PRP group showed significant advantages over the placebo group in terms of MCID at the first month (p = 0.03) and sixth months (p = 0.008), while there was no significant difference between the two groups at the third month (p = 0.19). Additionally, in terms of IIEF, PRP showed significantly better efficacy than placebo at the first, third, and sixth months (p < 0.00001). CONCLUSIONS: PRP shows more effectiveness in treating ED compared to placebo, offering hope as a potential alternative treatment for ED.

The pooled analysis evaluates the therapeutic efficacy of desmopressin combined with anticholinergic drugs in the treatment of pediatric nocturnal enuresis.

OBJECTIVE: This pooled analysis aims to demonstrate the clinical efficacy and safety of combined desmopressin and anticholinergic therapy in the treatment of pediatric nocturnal enuresis (NE). METHODS: A systematic search was conducted through PubMed, MEDLINE, EMBASE, ResearchGate, and Cochrane Library to identify all randomized controlled trials (RCTs) comparing monotherapy with desmopressin versus combined therapy with desmopressin and anticholinergic agents for the treatment of NE. Data analysis was performed using RevMan version 5.4.1. RESULTS: This study included 8 RCTs involving a total of 659 patients. The frequencies of complete response (CR), partial response (PR), and nonresponse (NR) were computed for both short-term treatment (1 month) and long-term treatment (3 months). Additionally, alterations in the mean number of NE episodes, adverse events, and relapse were assessed. Our analysis indicates that, in comparison to the monotherapy group, the combination therapy group plays a pivotal role in augmenting the CR odds and diminishing the NR ratios in both short-term and long-term treatments (1 month CR ratio [risk ratio (RR): 1.84; 95% confidence interval (CI): 1.22-2.76; p = 0.003, I2 = 72%]; 3 months CR ratio [RR: 1.48; 95% CI: 1.25-1.76; p < 0.00001, I2 = 0%]; 1 month NR ratio [RR: 0.67; 95% CI: 0.55-0.82; p = 0.0001, I2 = 0%]; 3 months CR ratio [RR: 0.37; 95% CI: 0.19-0.73; p = 0.004, I2 = 0%]). Furthermore, in both short-term and long-term treatment, the combined therapy group exhibits a greater magnitude of change in the average number of NE episodes compared to patients receiving monotherapy (1 month, mean difference [MD] = -2.97; 95% CI: -4.23 to -1.71, p < 0.0001; 3 months, MD = -4.30; 95% CI: -7.18 to -1.43, p = 0.003). Moreover, the combination therapy group exhibits a significant reduction in the recurrence rate (RR: 0.36; 95% CI: 0.15-0.86; p = 0.02). There is no significant difference in the incidence of adverse events between the two groups (RR: 1.16; 95% CI: 0.58-2.31; p = 0.67). CONCLUSION: Combining desmopressin with anticholinergic medications is more effective for NE than desmopressin alone, with lower recurrence and minimal adverse effects.

Updated recommendations on the therapeutic role of extracorporeal shock wave therapy for peyronie's disease: systematic review and meta-analysis.

BACKGROUND: The therapeutic role of extracorporeal shockwave therapy (ESWT) for Peyronie's disease (PD) has been controversial in a long term. We aimed to further evaluate the therapeutic effect of ESWT for PD on the basis of available high-quality studies. METHODS: The PubMed, CENTRAL and Embase databases were searched for articles published from January 1st, 2000 to December 31, 2022. Only randomized controlled trials (RCTs) using ESWT to treat PD were included. Meta-analysis and forest plots were carried out using Review Manager 5.4.1 software, and outcomes were reviewed by 2 authors independently. Using the Risk of Bias assessment form (ROB-2) by Cochrane Collaboration for quality assessment. PRISMA 2020 guidelines were used in this article to achieve the quantitative and qualitative synthesis of data. RESULTS: A total of four RCTs were included. 151 patients in the ESWT group and 150 patients in the control group. The meta-analysis results showed that ESWT could significantly reduce plaque size (OR 2.59, 95%CI 1.15 to 5.85, P = 0.02) and relieve pain (MD -1.55, 95%CI -2.46 to -0.64, P = 0.0008); but it has no significant effect on reducing the penile curvature (OR 1.93, 95%CI 0.87-4.26, P = 0.11) and improving sexual function (MD 2.6, 95%CI -1.63 to 6.83, P = 0.23), there is also no significant difference in complication rates between groups (OR 2.94, 95%CI 0.66 to 13.03, P = 0.16). The risk of bias of results is low. The limitations of this study are that the number of included studies is too small, some experimental outcomes are missing, and the expression of outcomes is not unified. CONCLUSIONS: For PD, ESWT can be considered as a safe short-term treatment, which can reduce plaque size and relieve pain, but cannot improve penile curvature and sexual function. Its long-term efficacy remains to be discussed. REGISTRATION NUMBER: PROSPERO (ID: CRD42023436744).

Robot-assisted radical cystectomy vs open radical cystectomy in patients with bladder cancer: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Even though there isn't enough clinical evidence to demonstrate that robot-assisted radical cystectomy (RARC) is preferable to open radical cystectomy (ORC), RARC has become a widely used alternative. We performed the present study of RARC vs ORC with a focus on oncologic, pathological, perioperative, and complication-related outcomes and health-related quality of life (QOL). METHODS: We conducted a literature review up to August 2022. The search included PubMed, EMBASE and Cochrane controlled trials register databases. We classified the studies according to version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). The data was assessed by Review Manager 5.4.0. RESULTS: 8 RCTs comparing 1024 patients were analyzed in our study. RARC was related to lower estimated blood loss (weighted mean difference (WMD): -328.2; 95% CI -463.49--192.92; p < 0.00001), lower blood transfusion rates (OR: 0.45; 95% CI 0.32 - 0.65; p < 0.0001) but longer operation time (WMD: 84.21; 95% CI 46.20 -121.72; p < 0.0001). And we found no significant difference in terms of positive surgical margins (P = 0.97), lymph node yield (P = 0.30) and length of stay (P = 0.99). Moreover, no significant difference was found between the two groups in terms of survival outcomes, pathological outcomes, postoperative complication outcomes and health-related QOL. CONCLUSION: Based on the present evidence, we demonstrated that RARC and ORC have similar cancer control results. RARC is related to less blood loss and lower transfusion rate. We found no difference in postoperative complications and health-related QOL between robotic and open approaches. RARC procedures could be used as an alternate treatment for bladder cancer patients. Additional RCTs with long-term follow-up are needed to validate this observation.

The efficacy of CO2 laser in the treatment of genitourinary syndrome of menopause: a systematic review and meta-analysis of randomized controlled trials.

CO2 laser has been proposed as a treatment strategy for genitourinary syndrome of menopause (GSM). In order to assess its efficacy for treating GSM, we conducted a systematic review and meta-analysis. To identify the current state of randomized controlled trials on CO2 laser therapy for GSM, a literature review was conducted. We systematically searched the following databases: PUBMED, EMBASE and the Cochrane Controlled Trials Register. In addition, a review of the references in the retrieved studies was carried out. Of 562 identified studies, 9 were eligible and were included in our analysis, involving 523 patients in total. Based on our analysis, CO2 laser has no statistical difference compared with estrogen in VHI (p = 0.87), FSFI total score (p = 0.19), FSFI-Arousal (p = 0.11), FSFI-Desire (p = 0.72), FSFI-Orgasm (p = 0.45) and FSFI-Satisfaction (p = 0.08). The meta-analysis also showed that CO2 laser significantly improved FSFI-Lubrication scores compared with estrogen therapy (p = 0.0004). Furthermore, compared with the sham group, CO2 laser group had statistically improved VHI scores (p = 0.003) and FSFI scores (p < 0.00001). CO2 laser therapy may be an effective alternative to estrogen therapy for GSM both in cases where estrogen is not applicable because of comorbidities and in cases in which women do not desire to take estrogen.

A systematic review and meta-analysis of efficacy and safety comparing greenlight laser vaporization with transurethral resection of the prostate for benign prostatic hyperplasia with prostate volume less than 80 ml.

We conducted a meta-analysis to evaluate the efficacy and safety of photo selective vaporisation of the prostate (PVP) with the GreenLight Laser versus transurethral resection of the prostate (TURP) for the treatment of small-volume benign prostatic hyperplasia (BPH). As of July 2022, relevant literature in online databases such as Cochrane Library, PubMed, and Embase was searched, including studies published on or before that date, and there were 9 studies in total, including 5 RCTs and 4 non-RCTs. In total 1525 patients were included to compare the efficacy of PVP and TURP in treating BPH. The Cochrane Collaboration criteria were used to evaluate the risk of bias. The software was used for random effect meta-analysis with RevMan 5.3. Data extraction included: clinical baseline characteristics, perioperative parameters, complication rates, International Prostate Symptom Score (IPSS), prostate specific antigen (PSA), post-void residual urine (PVR), maximum flow rate (Qmax), and quality of life (QoL). The pooled analysis showed that PVP was associated with reduced blood loss, blood transfusion, clot retention, catheterization time, definitive catheter removal, and hospital stay, but was associated with longer operative time and more severe dysuria (all p < 0.05). The results of this meta-analysis show that PVP as a technique for the treatment of benign prostatic hyperplasia with a volume of less than 80 cc has similar efficacy to standard TURP in IPSS, PSA, PVR, Qmax and QoL, and is an effective alternative. It outperformed TURP in terms of blood transfusion, catheterization time and hospital stay, while TURP is superior to PVP in terms of operation time.

The application of internal traction technique in retroperitoneal robot-assisted partial nephrectomy for renal ventral tumors.

BACKGROUND: For patients with prior intra-abdominal surgery or multiple arteries, the retroperitoneal robot-assisted partial nephrectomy (rRAPN) is a better choice. The renal ventral tumor poses an additional challenge due to poor tumor exposure. This study is determined to assess the feasibility of an internal traction technique (ITT) in rRAPN for the management of renal ventral tumors. METHODS: From November 2019 to March 2021, a total of 28 patients with renal ventral tumor underwent rRAPN. All patients had prior abdominal surgery or multiple arteries. The ITT group (20 patients), which improved the tumor exposure by traction of the kidney with suture, was compared with the traditional technique group (8 patients) in terms of warm ischemia time, estimated blood loss and postoperative hospital stay, retroperitoneal drainage, R.E.N.A.L. score, and serum creatinine. Differences were considered significant when P < 0.05. RESULTS: All rRAPN surgeries were successful without conversion to radical nephrectomy or open partial nephrectomy. The warm ischemia time was lower in the ITT group (17.10 min vs. 24.63 min; P < 0.05). Estimated blood loss in the traditional technique group was 324.88 ± 79.42 mL, and in the ITT group, it was 117.45±35.25 mL (P < 0.05). No significant differences with regard to postoperative hospital stay, retroperitoneal drainage, R.E.N.A.L. score, and serum creatinine were observed between both groups. Surgical margins were negative and no intraoperative complications occurred in all the patients. After 10 months of follow-up, no recurrence or metastasis occurred in all cases. CONCLUSION: ITT is a feasible, safe, and valid procedure in rRAPN for renal ventral tumors. Application of ITT improved the exposure and reduces warm ischemic time in comparison with the conventional procedure.

Robot-assisted versus conventional laparoscopic partial nephrectomy for renal hilar tumors: Parenchymal preservation and functional recovery.

OBJECTIVE: To determine whether robot-assisted laparoscopic partial nephrectomy (RALPN) can benefit patients in terms of functional recovery in the treatment of renal hilar tumors compared to conventional laparoscopic partial nephrectomy (CLPN). METHODS: Between January 2019 and July 2021, patients with hilar tumors who underwent partial nephrectomy (PN) were acquired at our center and were classified into RALPN and CLPN groups. Ipsilateral parenchymal volume (IPV) and glomerular filtration rate (GFR) were determined independently 3-5 days before and 3 months after PN using contrast-enhanced computed tomography and nuclear renal scans. Pearson correlation was used to determine the link between ipsilateral GFR preservation and IPV preserved. Concurrently, multivariable analysis was employed to determine characteristics associated with functional recovery. RESULTS: A total of 96 patients with hilar tumors were studied, of which 41 received RALPN and 55 received CLPN. Excisional parenchymal volume was 27 and 37 cm3 (p = 0.005) in RALPN and CLPN groups, respectively, and IPV preserved was 77% and 68% (p < 0.001). Furthermore, the ipsilateral GFR preserved was 77.7% and 75.3%, respectively (p = 0.003). On Pearson correlation, ipsilateral GFR preservation was linked with IPV preserved (r = 0.36, p < 0.001). According to a multivariate study, baseline GFR, IPV preserved, and surgical procedures (RALPN vs. CLPN) were significant factors influencing functional recovery. CONCLUSION: Our study suggests that RALPN, rather than CLPN, can achieve better functional recovery in the treatment of hilar tumors due to its ability to win more IPV preserved. RALPN should be recommended as the first-line treatment for hilar tumors, but randomized controlled trials are required to validate our findings.

LINC01410 leads the migration, invasion and EMT of bladder cancer cells by modulating miR-4319 / Snail1.

BACKGROUND: Several previous studies have implied the significance of lncRNA1410 (LINC01410) in gastric cancer, rectal cancer, and cervical cancer. Nevertheless, the potential of LINC01410 in bladder cancer (BC) development has not been addressed. METHODS: The related mechanisms were explored by qRT-PCR analysis, CCK-8 assay, cell transfection assay, Transwell assay, Western Blot analysis, Luciferase reporter assay and RNA pull-down assay. RESULTS: In the following study, LINC01410, characterized as an oncogene, exhibited high levels of expression in BC tissues as compared to normal tissues and its expression leads to a reduced prognosis of BC. Functional characterization of LINC01410 showed that knocking down LINC01410 could markedly reduce the invasion and proliferation capacity of T24 and 5637 cells. Mechanistically, LINC01410 served as a sponge for miR-4319 and the findings were further attested through luciferase reporter assay. Analysis of miR-4319 demonstrated its low expression in BC tissues as compared to normal tissues and knocking down LINC01410 significantly increased miR-4319. Data obtained from rescue assay discovered that silencing of miR-4319 in T24 and 5637 cells restored the proliferation and invasion capacity of LINC01410. CONCLUSIONS: Taken together, this study is the first report on the oncogenic potential of LINC01410 in BC development by upregulating Snail1 protein and downregulating miR-4319. Trial registration Retrospectively registered.

Xanthogranulomatous pyelonephritis infected with the Providencia stuartii: a case report and literature review.

BACKGROUND: Xanthogranulomatous pyelonephritis (XGP) is a rare and severe chronic inflammatory disease of the renal parenchyma, which is most commonly associated with super-infections by bacteria such as E. coli, Proteus mirabilis, and occasionally Pseudomonas species. CASE PRESENTATION: Herein, we present a rare case of a patient with XGP infected with Providencia stuartii. Initially, the patient refused nephrectomy and underwent holmium laser lithotripsy and right ureteral stenting, followed by meropenem treatment of 7 days. Relapse occurred in the third month after discharge from the hospital, due to which she underwent a radical nephrectomy. DISCUSSION: The diagnosis of XGP is confirmed by histopathology. The standard treatment for XGP is antibiotic therapy and radical nephrectomy, but partial nephrectomy may be appropriate in select cases.

Impact of differential ureteral stent diameters on clinical outcomes after ureteroscopy intracorporeal lithotripsy: A systematic review and meta-analysis.

In this meta-analysis we assessed whether the diameter of ureteral stents (4.7-5-Fr, 6-Fr) has an impact on the rate of occurrence of urinary tract symptoms and complications after successful URS and intracorporeal lithotripsy. A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A rigorous search for relevant studies published in MEDLINE, Embase, and the Cochrane Controlled Trials Register was conducted to find informative randomized controlled trials. The reference lists of relevant articles were also manually searched and reviewed. The protocol was prospectively registered at PROSPERO (CRD42020202164). All statistical evaluations were performed using RevMan software version 5.3.0. Seven articles comprising 547 patients were included in the meta-analysis. After placement of ureteral stents with different diameters for approximately 1 week, we found that ureteral stents with smaller diameters (4.7-5-Fr) were associated with significant improvements in the main domain scores on the Ureteral Stent Symptom Questionnaire, such as urinary symptoms (mean difference -4.47, 95% confidence interval -5.87 to -3.08; P < 0.00001) and body pain (mean difference -2.48, 95% confidence interval -4.37 to -0.59; P = 0.01), but poor outcomes in stent migration compared to ureteral stents with a 6-Fr diameter (odds ratio 3.00, 95% confidence interval 1.06-8.51; P = 0.04). However, there were no significant differences in Ureteral Stent Symptom Questionnaire scores with regard to work performance (mean difference -0.56, 95% confidence interval -2.52 to 1.40; P = 0.58), general health (mean difference -2.29, 95% confidence interval -4.95 to 0.37; P = 0.09), additional problems (mean difference -0.43, 95% confidence interval -1.02 to 0.15; P = 0.15), and complications such as fever (odds ratio 0.75, 95% confidence interval 0.24-2.39; P = 0.63). Ureteral stents with a diameter of 4.7-5-Fr have better outcomes than those with a diameter of 6-Fr, based on the Ureteral Stent Symptom Questionnaire pain and urinary tract symptoms scores. However, they are more prone to migration compared to those with a larger diameter.

Importance of PNO1 for growth and survival of urinary bladder carcinoma: Role in core-regulatory circuitry.

PNO1 (partner of Nob1) was known as a RNA-binding protein in humans, and its ortholog PNO1 was reported to participate ribosome and proteasome biogenesis in yeasts. Yet there have been few studies about its functions in mammalian cells, and so far its role in human cells has never been reported, especially in urinary bladder cancer (UBC).We interrogated the cellular functions and clinical significance of PNO1 in, and its molecular mechanism through microarrays and bioinformatics analysis. Our findings support that PNO1 participates in promoting proliferation and colonogenesis, while reducing apoptosis of UBC cells, and is also predicted to be associated with the migration and metastasis of UBC PNO1 knockdown (KD) attenuated the tumorigenesis ability of UBC in mouse. PNO1 KD led to the altered expression of 1543 genes that are involved in a number of signalling pathways, biological functions and regulation networks. CD44, PTGS2, cyclin D1, CDK1, IL-8, FRA1, as well as mTOR, p70 S6 kinase, p38 and Caspase-3 proteins were all down-regulated in PNO1 KD cells, suggesting the involvement of PNO1 in inflammatory responses, cell cycle regulation, chemotaxis, cell growth and proliferation, apoptosis, cell migration and invasiveness. This study will enhance our understanding of the molecular mechanism of UBC and may eventually provide novel targets for individualized cancer therapy.

Bilateral corpus callosum and corona radiata infarction due to cerebral venous sinus thrombosis presenting as headache and acute reversible aphasia: a rare case report.

BACKGROUND: Cerebral venous sinus thrombosis (CVST), a rare cause of cerebral infarction, is often unrecognized at initial presentation. We report the case of a patient with bilateral corpus callosum and corona radiata infarction due to cerebral venous sinus thrombosis presenting as headache and acute reversible aphasia. CASE PRESENTATION: A 30-year-old female patient presented with headache, vomiting, and motor aphasia. She was 20 days post-partum and had a lower than normal food intake following a normal vaginal delivery. Brain magnetic resonance images revealed a bilateral corpus callosum and corona radiata infarction. MR venography (MRV) and digital subtraction angiography (DSA) images showed a signal void in the anterior aspect of the superior sagittal sinus and inferior sagittal sinus, ophthalmic vein expansion, and the reversed direction of venous flow. In addition, images showed non-visualization of the left transverse sinus. The left slender sigmoid sinus and small internal jugular vein were also noted. The diagnosis of cerebral venous thrombosis was considered based on the above findings. The patient was managed with anticoagulation therapy, and recovered substantially after treatment. CONCLUSIONS: Bilateral corpus callosum and corona radiata infarction is very rare. However, for patients who clinically show cranial hypertension and neurological deficits during the puerperium period, the possibility of CVST should be considered. Furthermore, DSA plays an important role in the diagnosis of CVST, and should be routinely checked. Early diagnosis is crucial for the patient suffering from CVST.

Predictive value of single-nucleotide polymorphism signature for recurrence in localised renal cell carcinoma: a retrospective analysis and multicentre validation study.

BACKGROUND: Identification of high-risk localised renal cell carcinoma is key for the selection of patients for adjuvant treatment who are at truly higher risk of reccurrence. We developed a classifier based on single-nucleotide polymorphisms (SNPs) to improve the predictive accuracy for renal cell carcinoma recurrence and investigated whether intratumour heterogeneity affected the precision of the classifier. METHODS: In this retrospective analysis and multicentre validation study, we used paraffin-embedded specimens from the training set of 227 patients from Sun Yat-sen University (Guangzhou, Guangdong, China) with localised clear cell renal cell carcinoma to examine 44 potential recurrence-associated SNPs, which were identified by exploratory bioinformatics analyses of a genome-wide association study from The Cancer Genome Atlas (TCGA) Kidney Renal Clear Cell Carcinoma (KIRC) dataset (n=114, 906 600 SNPs). We developed a six-SNP-based classifier by use of LASSO Cox regression, based on the association between SNP status and patients' recurrence-free survival. Intratumour heterogeneity was investigated from two other regions within the same tumours in the training set. The six-SNP-based classifier was validated in the internal testing set (n=226), the independent validation set (Chinese multicentre study; 428 patients treated between Jan 1, 2004 and Dec 31, 2012, at three hospitals in China), and TCGA set (441 retrospectively identified patients who underwent resection between 1998 and 2010 for localised clear cell renal cell carcinoma in the USA). The main outcome was recurrence-free survival; the secondary outcome was overall survival. FINDINGS: Although intratumour heterogeneity was found in 48 (23%) of 206 cases in the internal testing set with complete SNP information, the predictive accuracy of the six-SNP-based classifier was similar in the three different regions of the training set (areas under the curve [AUC] at 5 years: 0·749 [95% CI 0·660-0·826] in region 1, 0·734 [0·651-0·814] in region 2, and 0·736 [0·649-0·824] in region 3). The six-SNP-based classifier precisely predicted recurrence-free survival of patients in three validation sets (hazard ratio [HR] 5·32 [95% CI 2·81-10·07] in the internal testing set, 5·39 [3·38-8·59] in the independent validation set, and 4·62 [2·48-8·61] in the TCGA set; all p<0·0001), independently of patient age or sex and tumour stage, grade, or necrosis. The classifier and the clinicopathological risk factors (tumour stage, grade, and necrosis) were combined to construct a nomogram, which had a predictive accuracy significantly higher than that of each variable alone (AUC at 5 years 0·811 [95% CI 0·756-0·861]). INTERPRETATION: Our six-SNP-based classifier could be a practical and reliable predictor that can complement the existing staging system for prediction of localised renal cell carcinoma recurrence after surgery, which might enable physicians to make more informed treatment decisions about adjuvant therapy. Intratumour heterogeneity does not seem to hamper the accuracy of the six-SNP-based classifier as a reliable predictor of recurrence. The classifier has the potential to guide treatment decisions for patients at differing risks of recurrence. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Provincial Science and Technology Foundation of China, and Guangzhou Science and Technology Foundation of China.

CTCF regulates the FoxO signaling pathway to affect the progression of prostate cancer.

The present research focuses on the influence of CCCTC-binding factor (CTCF) on prostate cancer (PC) via the regulation of the FoxO signalling pathway. A bioinformatics analysis was conducted to screen out target genes for CTCF in LNCaP cells and to enrich the relevant pathways in LNCaP cells. It was found that the FoxO pathway was enriched according to the ChIP-seq results of CTCF. The expression of CTCF, pFoxO1a, FoxO1a, pFoxO3a and FoxO3a was tested by RT-qPCR and Western blot. Inhibition of CTCF could lead to the up-regulation of the FoxO signalling pathway. The rates of cell proliferation, cell invasion and apoptosis were examined by MTT assay, cell invasion assay and flow cytometry under different interference conditions. Down-regulation of CTCF could suppress cell proliferation, cell invasion and facilitate cell apoptosis. Lastly, the effect of CTCF on tumour growth was determined in nude mice. Inhibition of CTCF regulated the FoxO signalling pathway, which retarded tumour growth in vivo. In conclusion, CTCF regulates the FoxO signalling pathway to affect the progress of PC.

Ketamine induces reactive oxygen species and enhances autophagy in SV-HUC-1 human uroepithelial cells.

This study was aimed at exploring the underlying mechanisms of ketamine in the SV-40 immortalized human ureteral epithelial (SV-HUC-1) cells. The viability and apoptosis of SV-HUC-1 cells treated with 0.01, 0.1, and 1 mM ketamine were respectively detected via cell counting kit-8 (CCK-8) assay and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining. Reactive oxygen species (ROS) level was measured through ROS probe staining. Apoptosis-related proteins (B-cell lymphoma 2 [Bcl-2] and Bax) and autophagy-associated proteins (light chain 3-I [LC3-I] and LC3-II) were determined by western blot or immunofluorescent assay. Additionally, transmission electron microscopy (TEM) was used to evaluate the formation of autophagosomes. After cotreatment of 3-methyladenine (3-MA) or N-acetyl-l-cysteine (NAC), the biological functions of SV-HUC-1 cells were analyzed to determine the association of ROS with cell viability and autophagy. CCK-8 assay and TUNEL staining indicated that ketamine effectively decreased the viability of SV-HUC-1 cells and accelerated apoptosis of SV-HUC-1 cells through regulating the expression level of IKBα (phospho), nuclear factor ÐºB (P65), Bcl-2, and Bax proteins. Enhanced ROS production was also confirmed in ketamine-treated SV-HUC-1 cells treated with ketamine. Ketamine-induced autophagosomes in SV-HUC-1 cells were observed by means of TEM, and increased levels of LC3 II/I ratio and Beclin 1 were examined through western blot and immunofluorescent assay. Furthermore, ketamine exerted effects on SV-HUC-1 cells in a dose-dependent and time-dependent manner. Additionally, cotreatment of NAC with 3-MA significantly attenuated the ROS level and suppressed the cell autophagy. Ketamine promoted SV-HUC-1 cell autophagy and impaired the cell viability of SV-HUC-1 cells by inducing ROS.

Renal Cancer Surgery in Patients without Preexisting Chronic Kidney Disease-Is There a Survival Benefit for Partial Nephrectomy?

PURPOSE: Retrospective studies suggest that partial nephrectomy provides improved survival compared to radical nephrectomy even when performed electively. However, selection bias may contribute. We evaluated factors associated with nonrenal cancer related mortality after partial and radical nephrectomy in patients with a preoperative glomerular filtration rate of 60 ml/minute/1.73 m2 or greater. MATERIALS AND METHODS: We retrospectively evaluated the records of 3,133 patients with a preoperative glomerular filtration rate of 60 ml/minute/1.73 m2 or greater who underwent partial or radical nephrectomy. Nonrenal cancer related mortality was analyzed by the Kaplan-Meier test based on procedure and functional parameters, including the new baseline glomerular filtration rate. We used the Cox proportional hazards model to assess factors associated with nonrenal cancer related mortality among patients with a new baseline rate of 45 ml/minute/1.73 m2 or greater. RESULTS: Overall median age was 59 years and the median preoperative glomerular filtration rate was 85 ml/minute/1.73 m2. The new baseline glomerular filtration rate was 80 and 63 ml/minute/1.73 m2 and 10-year nonrenal cancer related mortality was 11.3% and 17.7% after partial and radical nephrectomy, respectively (each p <0.001). Median followup was 9.3 years. Nonrenal cancer related mortality was similar in all patients with a new baseline glomerular filtration rate of 45 ml/minute/1.73 m2 or greater (p = 0.26). However, it increased 50% or more in the 290 patients with a new baseline below this level (p = 0.001). In patients with a new baseline greater than 45 ml/minute/1.73 m2 10-year nonrenal cancer related mortality was still substantially improved after partial nephrectomy (10.6% vs 16.3%, p <0.001). In this population age, gender and partial vs radical nephrectomy were associated with nonrenal cancer related mortality on multivariable analysis (all p ≤0.001). In contrast, the increased new baseline glomerular filtration rate, as seen for partial nephrectomy, was not associated with reduced nonrenal cancer related mortality. CONCLUSIONS: In patients with a glomerular filtration rate of 60 ml/minute/1.73 m2 or greater who undergo partial or radical nephrectomy our data suggest that treatment should achieve a new baseline of 45 ml/minute/1.73 m2 or greater if feasible. Partial nephrectomy should be prioritized if needed to accomplish this. In patients with a new baseline rate of 45 ml/minute/1.73 m2 or greater partial nephrectomy was associated with improved survival. However, the functional dividend, namely the increased new baseline rate, failed to correlate, suggesting that selection bias may also impact outcomes.

Meta-analysis of efficacy and safety of continuous saline bladder irrigation compared with intravesical chemotherapy after transurethral resection of bladder tumors.

PURPOSE: We performed a meta-analysis to confirm the efficacy and safety of continuous saline bladder irrigation compared with intravesical chemotherapy after transurethral resection for the treatment of non-muscle invasive bladder cancer. METHODS: Randomized controlled trials of continuous saline bladder irrigation compared with intravesical chemotherapy were searched using MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. The data were evaluated and statistically analyzed using RevMan version 5.3.0. RESULTS: Four studies including 861 participants which compared continuous saline bladder irrigation with intravesical chemotherapy were considered. One-year recurrence-free survival [odds ratio (OR) = 0.76, 95% CI = 0.55-1.05, p = 0.09]; 2-year recurrence-free survival (OR = 0.94, 95% CI = 0.71-1.25, p = 0.68); the median period to first recurrence (OR = - 1.01, 95% CI = - 2.96 to 0.94, p = 0.31); the number of tumor progression (OR = 0.80, 95% CI = 0.54-1.17, p = 0.25); and the number of recurrence during follow-up (OR = 1.12, 95% CI = 0.84-1.50, p = 0.43) suggested that two methods of postoperative perfusion had no significant differences. In terms of safety, including macrohematuria, frequency of urination and bladder irritation symptoms, continuous saline bladder irrigation showed better tolerance than intravesical chemotherapy. CONCLUSION: Continuous saline bladder irrigation seems to provide a better balance between prevention of recurrence and local toxicities than intravesical chemotherapy after transurethral resection of bladder tumors.