Effects of the T-786C,G894T,and Intron 4 VNTR (4a/b) polymorphisms of the endothelial nitric oxide synthase gene on the risk of prostate cancer

Several studies have shown that nitric oxide (NO) and nitric oxide synthase (NOS) system plays an important role in carcinogenesis. Endothelial nitric oxide synthase (eNOS) gene polymorphisms significantly affects serum NO concentrations. Studies addressing the relationship between eNOS gene polymorphisms and prostate cancer (CaP) are very scarce. We examined the association between the 3 eNOS gene polymorphisms (T-786C, G894T, and 4a/b) with risk and clinical features of CaP. One hundred seventy patients with CaP (mean age 63.6 ± 12.4 years) and 340 age-matched healthy controls (mean age 64.9 ± 12.9 years) were recruited in this case-control study. Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique. For T-786C polymorphism, we found that CC genotype was associated to CaP risk [odds ratio (OR) = 3.62, 95% confidence interval (CI): 1.89–7.74, P = 0.002), high grade tumor (OR = 2.46, 95% CI:1.78–4.72; P = 0.006), and advanced disease (OR = 4.67, 95% CI: 2.64?8.61; P = 0.002). Neither the CaP risk nor clinical features of CaP were associated with the G894T polymorphism. It was found that, compared with 4a/b bb genotype, the 4a/b “a” variant genotypes were associated with an increased risk of CaP in an allele dose dependent manner (OR = 2.12, 95% CI: 1.68–3.44; P = 0.031 for 4a/b ab genotype, and OR = 4.32, 95% CI: 2.21–6.08; P = 0.001 for 4a/b aa genotype). In addition, genotypes with the “a” allele of the eNOS 4a/b polymorphism predispose the patients to high grade (OR = 4.76, 95% CI: 2.74–8.62; P = 0.001) and advanced CaP (OR = 5.28, 95% CI: 3.64–8.72; P = 0.001). Furthermore, the T-Asp-b and C-Asp-b haplotypes were associated with a significantly decreased risk of CaP (OR = 0.44, 95% CI: 0.33–0.77; P = 0.004, and OR = 0.39, 95% CI: 0.26–0.61; P = 0.001, respectively). We found significant differences in genotype distribution and allelic frequencies between CaP patients and controls for the T-786C, and 4a/b eNOS polymorphisms.     

A replication study examining association of rs6983267, rs10090154, and rs1447295 common single nucleotide polymorphisms in 8q24 region with prostate cancer in Siberians

IntroductionMultiple genetic studies have confirmed association of 8q24 variants with susceptibility to prostate cancer (CaP). However, the risk conferred in men living in Russia is unknown.Materials and methodsIn this work we studied the association of rs6983267, rs10090154, and rs1447295 single nucleotide polymorphisms (SNPs) with a risk of CaP development in men of Caucasoid descent living in the Siberian region of Russia. Three 8q24 SNPs were genotyped by real-time polymerase chain reaction in histologically confirmed CaP “cases” (n = 392) and clinically evaluated “controls” (n = 344). To evaluate the SNP effects on CaP susceptibility, odds ratio (OR) and confidence interval (CI) 95% were calculated. Allele and genotype frequencies in the groups were compared using logistic regression; differences were considered statistically significant if P<0.05.ResultsWe showed statistically significant association of the A allele of rs1447295 (OR [CI 95%] = 1.96 [1.37–2.81], P<0.0001) and the T allele of rs10090154 (OR [CI 95%] = 2.14 [1.41–3.26], P<0.0001) with CaP. The T-A rs10090154 to rs1447295 haplotype was also associated with CaP (OR [CI 95%] = 2.47 [1.59–3.85], P<0.0001). There was no significant association with the T allele of rs6983267: OR [CI 95%] = 0.9 [0.73–1.11], P> 0.05.ConclusionThus, our investigation confirms the role of chromosomal region 8q24 in the development of CaP in the Russian population.     

Abdominal obesity as risk factor for prostate cancer diagnosis and high grade disease: A prospective multicenter Italian cohort study

ObjectiveTo evaluate the association between abdominal obesity and prostate cancer (CaP) diagnosis and grade in patients undergoing prostate biopsy.Materials and methodsBetween 2008 and 2011, we prospectively enrolled patients referred to 3 clinics in Italy who were scheduled for transrectal ultrasound (TRUS) guided prostate biopsy. Before biopsy, digital rectal examination (DRE), prostate specific antigen (PSA), body mass index (BMI), and waist circumference (WC) were measured. Men were categorized in 4 groups of body habitus, according to BMI and waist circumference values. Crude and adjusted logistic regressions were performed to assess the association of BMI (continuous), waist circumference (continuous), body habitus (categorical), and CaP diagnosis and grade.ResultsSix hundred sixty-eight patients were enrolled. CaP was detected in 246 patients (38%), of whom 136 had low-grade (Gleason score ≤ 6) and 110 high-grade cancer (Gleason score ≥ 7). Logistic regression multivariate analysis showed that BMI (OR 1.05 per unit, CI 95% 1.00–1.10 P = 0.033) and waist circumference (OR 1.02 per cm, CI 95% 1.00–1.04 P = 0.026) were significant predictors of CaP diagnosis. BMI (OR 1.11 95% CI 1.04–1.18 P = 0.001) and WC (OR 1.04 95% CI 1.02–1.06 P = 0.001) were also associated with high-grade CaP. Furthermore, obesity with central adiposity (BMI ≥ 30kg/m² and WC ≥ 102 cm) was significantly associated with CaP diagnosis (OR 1.66, CI 95% 1.05–2.63, P = 0.03) and high-grade disease (OR 2.56, CI 95% 1.38–4.76, P = 0.003).ConclusionsObesity defined by BMI and WC seems to be associated with CaP and, more specifically, with high-grade disease at the time of biopsy. The relationship between obesity and CaP is complex and remains to be further addressed.     

8q24 and 17q Prostate cancer susceptibility loci in a multiethnic Asian cohort

ObjectivesRecently, several genome-wide association studies have demonstrated a cumulative association of 5 polymorphic variants in chromosomes 8q24 and 17q with prostate cancer (CaP) risk in Caucasians, particularly those harboring aggressive clinicopathologic characteristics. The purpose of this study was to evaluate the influence of these variants on CaP susceptibility in Singaporean Asian men.Materials and methodsWe performed a case-control study in 289 Chinese CaP patients and 412 healthy subjects (144 Chinese, 134 Malays, and 134 Indians), and examined the association of the 5 single nucleotide polymorphisms (SNPs) with CaP.ResultsIn the healthy subjects, rs16901979 A-allele frequency was highest amongst Chinese (0.32) compared with Malays (0.13; P < 0.0001) or Indians (0.09; P < 0.0001); rs6983267 G-allele was highest in Indians (0.51) compared with Chinese (0.42; P = 0.041) or Malays (0.43; P = 0.077); whereas rs1859962 G-allele frequency was highest amongst Indians (0.56) compared with Chinese (0.40; P = 0.0002) or Malays (0.38; P < 0.0001). Individuals with the rs4430796 TT genotype were at increased CaP risk in the Chinese via a recessive model (odds ratios (OR) = 1.56, 95% CI = 1.04–2.33). Significant associations were observed for rs4430796 TT with Gleason scores of ≥7 (OR = 1.76, 95% CI = 1.14–2.73) and prostate-specific antigen (PSA) levels of ≥10 ng/ml at diagnosis (OR = 1.63, 95% CI = 1.01–2.63), as well as for rs6983267 GG with stage 3–4 CaPs (OR = 1.91, 95% CI = 1.01–3.61). A cumulative gene interaction influence on disease risk, which approximately doubled for individuals with at least 2 susceptibility genotypes, was also identified (OR = 2.18, 95% CI = 1.10–4.32).ConclusionsThis exploratory analysis suggests that the 5 genetic variants previously described may contribute to prostate cancer risk in Singaporean men.     

Multicenter analysis of clinical and MRI characteristics associated with detecting clinically significant prostate cancer in PI-RADS (v2.0) category 3 lesions

ObjectivesWe sought to identify clinical and magnetic resonance imaging (MRI) characteristics in men with the Prostate Imaging - Reporting and Data System (PI-RADS) category 3 index lesions that predict clinically significant prostate cancer (CaP) on MRI targeted biopsy.Materials and MethodsMulticenter study of prospectively collected data for biopsy-naive men (n = 247) who underwent MRI-targeted and systematic biopsies for PI-RADS 3 index lesions. The primary endpoint was diagnosis of clinically significant CaP (Grade Group ≥2). Multivariable logistic regression models assessed for factors associated with clinically significant CaP. The probability distributions of clinically significant CaP based on different levels of predictors of multivariable models were plotted in a heatmap.ResultsMen with clinically significant CaP had smaller prostate volume (39.20 vs. 55.10 ml, P < 0.001) and lower apparent diffusion coefficient (ADC) values (973 vs. 1068 μm²/s, P = 0.013), but higher prostate-specific antigen (PSA) density (0.21 vs. 0.13 ng/ml², P = 0.027). On multivariable analyses, lower prostate volume (odds ratio [OR]: 0.95, 95% confidence interval [CI]: 0.92–0.97), lower ADC value (OR: 0.99, 95% CI: 0.99–1.00), and Prostate-specific antigen density >0.15 ng/ml² (OR: 3.51, 95% CI 1.61–7.68) were independently associated with significant CaP.ConclusionHigher PSA density, lower prostate volume and ADC values are associated with clinically significant CaP in biopsy-naïve men with PI-RADS 3 lesions. We present regression-derived probabilities of detecting clinically significant CaP based on various clinical and imaging values that can be used in decision-making. Our findings demonstrate an opportunity for MRI refinement or biomarker discovery to improve risk stratification for PI-RADS 3 lesions.     

Incidence,risk factors and outcomes of urethral recurrence after radical cystectomy for bladder cancer: A systematic review and meta-analysis

We aimed to conduct a systematic review and meta-analysis assessing the incidence and risk factors of urethral recurrence (UR) as well as summarizing data on survival outcomes in patients with UR after radical cystectomy (RC) for bladder cancer. The MEDLINE and EMBASE databases were searched in February 2021 for studies of patients with UR after RC. Incidence and risk factors of UR were the primary endpoints. The secondary endpoint was survival outcomes in patients who experienced UR. Twenty-one studies, comprising 9,435 patients, were included in the quantitative synthesis. Orthotopic neobladder (ONB) diversion was associated with a decreased probability of UR compared to non-ONB (pooled OR: 0.44, 95% CI: 0.31–0.61, P < 0.001) and male patients had a significantly higher risk of UR compared to female patients (pooled OR: 3.16, 95% CI: 1.83–5.47, P < 0.001). Among risk factors, prostatic urethral or prostatic stromal involvement (pooled HR: 5.44, 95% CI: 3.58–8.26, P < 0.001; pooled HR: 5.90, 95% CI: 1.82–19.17, P = 0.003, respectively) and tumor multifocality (pooled HR: 2.97, 95% CI: 2.05–4.29, P < 0.001) were associated with worse urethral recurrence-free survival. Neither tumor stage (P = 0.63) nor CIS (P = 0.72) were associated with worse urethral recurrence-free survival. Patients with UR had a 5-year CSS that varied from 47% to 63% and an OS - from 40% to 74%; UR did not appear to be related to worse survival outcomes. Male patients treated with non-ONB diversion as well as patients with prostatic involvement and tumor multifocality seem to be at the highest risk of UR after RC. Risk-adjusted standardized surveillance protocols should be developed into clinical practice after RC.     

Serum levels of chromogranin A are not predictive of high-grade,poorly differentiated prostate cancer: Results from an Italian biopsy cohort

ObjectivesTo explore the association of chromogranin A (CgA) levels and the risk of poorly differentiated prostate cancer (CaP) in men undergoing prostate biopsy.Materials and methodsBetween 2006 and 2012, we prospectively enrolled 1,018 men with no history of CaP undergoing prostate biopsy. The risk of detecting poorly differentiated CaP as a function of CgA concentration was evaluated using crude and adjusted logistic regressions. Further analyses were performed to determine whether CgA was a significant predictor of high-grade CaP in men with low PSA (<10 ng/ml).ResultsWe found a significantly higher level of CgA in men with poorly differentiated CaP. CgA was however co-linear with age, and serum CgA levels were not significantly associated with the overall risk of CaP, and the specific risk of poorly differentiated CaP (OR 1.001 95% CI 0.99–1.01, P = 0.74). Moreover, in men with low PSA levels (<10 ng/ml), CgA was not a significant predictor of high grade-disease on univariate (OR 1.00; 95% CI 0.99–1.01; P = 0.66) and multivariate analysis (P = 0.85).ConclusionsIn our cohort of patients, the serum level of CgA is not a significant predictor of poorly differentiated CaP on initial prostate biopsy, even in men with low PSA levels (<10 ng/ml). According to our experience, CgA should not be considered a reliable marker to predict poorly differentiate cancer in the setting of initial prostate biopsy.     

Radical prostatectomy then and now: Surgical overtreatment of prostate cancer is declining from 2009 to 2016 at a tertiary referral center

Background

In the era of increasing scrutiny of delivery of quality care, efforts to decrease surgical overtreatment of insignificant prostate cancer (iCaP) continue.

Pharmacological and nonpharmacological prevention of fentanyl-induced cough: a meta-analysis

Fentanyl-induced cough (FIC) is often observed after intravenous bolus administration of fentanyl during anesthesia induction. This meta-analysis assessed the efficacy of pharmacological and nonpharmacological interventions to reduce the incidence of FIC. We searched for randomized controlled trials comparing pharmacological or nonpharmacological interventions with controls to prevent FIC; we included 28 studies retrieved from PubMed, Embase, and Cochrane Library. Overall incidence of FIC was approximately 31 %. Lidocaine [odds ratio (OR)  = 0.29, 95 % confidence interval (CI) 0.21–0.39], N-methyl-D-aspartate (NMDA) receptor antagonists (OR 0.09, 95 % CI 0.02–0.42), propofol (OR 0.07, 95 % CI 0.01–0.36), α₂ agonists (OR 0.32, 95 % CI 0.21–0.48), β₂ agonists (OR 0.10, 95 % CI 0.03–0.30), fentanyl priming (OR 0.33, 95 % CI 0.19–0.56), and slow injection of fentanyl (OR 0.25, 95 % CI 0.11–0.58)] were effective in decreasing the incidence of FIC, whereas atropine (OR 1.10, 95 % CI 0.58–2.11) and benzodiazepines (OR 2.04, 95 % CI 1.33–3.13) were not effective. This meta-analysis found that lidocaine, NMDA receptor antagonists, propofol, α₂ agonists, β₂ agonists, and priming dose of fentanyl were effective in preventing FIC, but atropine and benzodiazepines were not. Slow injection of fentanyl was effective in preventing FIC, but results depend on the speed of administration.     

Prognostic role of Ki-67 score in localized prostate cancer: A systematic review and meta-analysis

Background

Ki-67 for quantifying tumor proliferation is widely used. In localized prostate cancer (PCa), despite a suggested predictive role of Ki-67 for outcomes after therapies, it has not been incorporated into clinical practice. Herein, we conduct a systematic review and meta-analysis of the literature reporting the association of Ki-67 and disease outcomes in PCa treated radically.

雌激素受体β与结直肠癌临床病理特征及预后关系的Meta分析

目的通过Meta分析来评价雌激素受体β表达与结直肠癌临床病理特征及预后的关系,为雌激素受体β在结直肠癌诊断和治疗中的作用提供循证医学证据。 方法检索中国知网、万方、Cochrane Library、PubMed、SpringerLink、EBSCO、MEDLINE等数据库,检索建库开始至2019年12月所有研究雌激素受体β与结直肠癌的文献,提取相关临床资料和数据,根据纳入和排除标准,并根据Cochrane文献质量评估手册评估文献质量,最后采用RevMan 5.3进行Meta分析。 结果最终8篇文献2 149例患者纳入分析。雌激素受体β表达阳性患者预后更好,差异有统计学意义（HR=0.74,95% CI：0.63~0.86,P=0.000 1）。雌激素受体β表达与肿瘤的浸润程度有关,差异有统计学意义（OR=1.44,95% CI：1.15~1.80,P=0.002）,而与性别（OR=1.17,95% CI：0.97~1.40,P=0.10）、肿瘤的分化程度（OR=0.96,95% CI：0.78~1.20,P=0.74）、淋巴结转移（OR=0.90,95% CI：0.74~1.11,P=0.33）、远处转移（OR=0.91,95% CI：0.67~1.23,P=0.55）等无关,差异无统计学意义。 结论雌激素受体β是结直肠癌的独立预后因子,在结直肠癌预后评估和治疗靶点方面具有重要作用。     

Getting back to equal: The influence of insurance status on racial disparities in the treatment of African American men with high-risk prostate cancer

ObjectivesTreating high-risk prostate cancer (CaP) with definitive therapy improves survival. We evaluated whether having health insurance reduces racial disparities in the use of definitive therapy for high-risk CaP.Materials and methodsThe Surveillance, Epidemiology, and End Results Program was used to identify 70,006 men with localized high-risk CaP (prostate-specific antigen level >20 ng/ml or Gleason score 8–10 or stage>cT3a) diagnosed from 2007 to 2010. We used multivariable logistic regression to analyze the 64,277 patients with complete data to determine the factors associated with receipt of definitive therapy.ResultsCompared with white men, African American (AA) men were significantly less likely to receive definitive treatment (adjusted odds ratio [AOR] = 0.60; 95% CI: 0.56–0.64; P<0.001) after adjusting for sociodemographics and known CaP prognostic factors. There was a significant interaction between race and insurance status (P_interaction = 0.01) such that insurance coverage was associated with a reduction in racial disparity between AA and white patients regarding receipt of definitive therapy. Specifically, the AOR for definitive treatment for AA vs. white was 0.38 (95% CI: 0.27–0.54, P<0.001) among uninsured men, whereas the AOR was 0.62 (95% CI: 0.57–0.66, P<0.001) among insured men.ConclusionsAA men with high-risk CaP were significantly less likely to receive potentially life-saving definitive treatment when compared with white men. Having health insurance was associated with a reduction in this racial treatment disparity, suggesting that expansion of health insurance coverage may help reduce racial disparities in the management of aggressive cancers.     

Effect of obesity on the prognosis and recurrence of prostate cancer after radical prostatectomy: a meta-analysis

BackgroundObesity has been found to be closely related to the increased risk of fatal prostate cancer (PCa), however there remains no evidence that further clarifies the relationship between obesity and the postoperative recurrence and poor prognosis of PCa. In this study, a systematic review and meta-analysis were performed to systematically evaluate the effect of obesity on the prognosis and recurrence of PCa after radical prostatectomy (RP).MethodsA literature search of the PubMed, Web of Science, and Embase databases was performed covering articles published between January 2013 and January 2020. Articles regarding the correlation between body mass index (BMI) and the prognosis and recurrence of PCa following RP were included in the meta-analysis. Two investigators independently screened the literature and extracted relevant data including publication information, key results, number of cancer cases, and multivariable-adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Meta-analysis was performed using RevMan 5.3 and Stata 16.0 software, and forest plots, funnel plots, and sensitivity analysis were also conducted.ResultsA total of 14 articles were included, all of which were analyzed for clinicopathological characteristics. Eight articles reported the biochemical recurrence (BCR) with prostate-specific antigen (PSA) as the predictor, and six articles reported the positive surgical margins (PSM). The meta-analysis showed that obese PCa patients had more postoperative recurrence and poor prognosis compared with the normal weight PCa patients, and the difference was statistically significant (OR =1.25, 95% CI: 1.10, 1.43). BCR exhibited no significant difference between obese and non-obese PCa patients after surgery (OR =1.2, 95% CI: 0.96, 1.46), and there were also no notable differences in PSM between the groups (OR =1.16, 95% CI: 0.99, 1.36). Subgroup analysis showed that obese PCa patients in the Americas (95% CI: 1.11, 1.37) and Europe (95% CI: 1.11, 1.78) were more likely to have surgical recurrence and poor prognosis (OR =1.40). Obese patients in the Americas were also more likely to have BCR after surgery (95% CI: 1.07, 1.36).ConclusionsObesity easily leads to poor prognosis and recurrence of PCa after RP.     

长链非编码RNA TUG1在骨肉瘤中的发生机制—系统回顾和荟萃分析

目的本研究旨在系统回顾长链非编码RNA TUG1（lncRNA TUG1）在骨肉瘤发生、发展中的机制,以及探讨TUG1在评估骨肉瘤患者预后中的价值。 方法系统检索PubMed、Embase、Web of Science、CochraneLibrary、中国知网（CNKI）和万方医学数据库,收集TUG1与骨肉瘤发生及预后的相关文献。系统回顾TUG1在骨肉瘤发生、发展中的机制,并采用Stata12软件（Stata公司,美国）对TUG1与骨肉瘤患者预后的相关性进行meta分析。 结果目前的研究表明,TUG1主要通过发挥竞争性内源RNA（competing endogenous RNA）效应调控骨肉瘤细胞增殖、凋亡和侵袭等过程,涉及通路包括AKT信号通路和Wnt/β-catenin信号通路。本研究共纳入4篇文献进行meta分析,共244例骨肉瘤患者。TUG1表达升高的骨肉瘤患者总体生存率低于TUG1表达降低的骨肉瘤患者（OR=1.921,95% CI：1.361,2.712,P=0.000）。不仅如此,骨肉瘤患者组织中TUG1表达升高往往提示肿瘤具有更大的体积（OR=4.084,95% CI：2.313,7.211,P=0.000）、较高的临床分级（OR=0.247,95% CI：0.133,0.539,P=0.000）和更早期远处转移（OR=1.943,95% CI：1.130,3.339,P=0.016）。然而,其与患者性别（OR=1.055,95% CI：0.620,1.793,P=0.844）和肿瘤发生部位（OR=0.806,95% CI：0.424,1.530,P=0.509）无显著相关性。 结论长链非编码RNATUG1与骨肉瘤发生、发展密切相关。不仅如此,TUG1表达升高提示骨肉瘤患者不良临床预后,其可能是一种评估骨肉瘤患者预后的生物学标志物。     

Comparison of Minimally Invasive and Traditionally Open Surgeries in Correction of Hallux Valgus: A Meta-Analysis

This meta-analysis aimed to compare the clinical outcomes of minimally invasive surgery (MIS) and traditional open surgery for the correction of symptomatic hallux valgus. A literature search was conducted, and a total of 11 studies with 1166 (52.98%, cases) patients treated with MIS and 1035 (47.02%, cases) patients treated with traditionally open surgery were included in the meta-analyses. The pooled data (odds ratio [OR] 6.28, 95% confidence interval [CI] 3.20 to 12.32, Z = 5.35, p < .01) indicated that patients treated with MIS had a significantly higher rate of excellent-good radiographic angular results than did patients treated with open surgery. However, the incidences of complications (OR 0.67, 95% CI 0.24 to 1.91, Z = 0.75, p = .45), recovery time (standard mean difference ‒3.09, 95% CI ‒7.98 to 1.80, Z = 1.24, p = .22), and patient-reported satisfaction (OR 2.76, 95% CI 0.72 to 10.65, Z = 1.48, p = .14) were similar between patients with hallux valgus treated with MIS and patients treated with open surgery. Heterogeneity between the sources of the pooled data threatened the validity of our observations, and we used statistical methods that aimed to limit such biases. At this time, more high-quality studies are needed to confirm or refute the results of this investigation.     

Prognostic value of preoperative blood-based biomarkers in upper tract urothelial carcinoma treated with nephroureterectomy: A systematic review and meta-analysis

Purpose: This systematic review and meta-analysis assessed the prognostic value of preoperative blood-based biomarkers in patients with upper tract urothelial carcinoma (UTUC) treated with nephroureterectomy. Methods: PUBMED, Web of Science, Cochrane Library, and Scopus databases were searched in June 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared cancer-specific survival in UTUC patients with and without pretreatment laboratory abnormalities. Formal meta-analyses were performed for this outcome. Results: The review identified 54 studies with 23,118 patients, of these, 52 studies with 22,513 patients were eligible for the meta-analysis. Several preoperative blood-based biomarkers were significantly associated with cancer-specific survival as follows: neutrophil-lymphocyte ratio (pooled hazard ratio [HR]: 1.66, 95% confidence interval [CI]: 1.34−2.06), C-reactive protein (pooled HR: 1.17, 95% CI: 1.07−1.29), platelet-lymphocyte ratio (pooled HR: 1.68, 95% CI: 1.30−2.17), white blood cell (pooled HR: 1.58, 95% CI: 1.02−2.46), De Ritis ratio (pooled HR: 2.40, 95% CI: 1.92−2.99), fibrinogen (pooled HR: 2.23, 95% CI: 1.86−2.68), albumin-globulin ratio (pooled HR: 3.00, 95% CI: 1.87−4.84), hemoglobin (pooled HR: 1.51, 95% CI: 1.22−1.87), and estimate glomerular filtration rate (pooled HR: 1.52, 95% CI: 1.19−1.94). The Cochrane's Q test and I² test revealed significant heterogeneity for neutrophil-lymphocyte ratio, C-reactive protein, white blood cell, hemoglobin, and estimated glomerular filtration rate (P = 0.022; I² = 50.7%, P = 0.000; I² = 80.4%, P = 0.000; I² = 88.3%, P = 0.010; I² = 62.0%, P = 0.000; I² = 83.9%, respectively). Conclusions: Several pretreatment laboratory abnormalities in patients with UTUC were associated with increased risks of cancer-specific mortality. Therefore, blood-based biomarkers may have the potential to serve as prognostic factors to assist patients and physicians in selecting appropriate treatment strategies for UTUC. However, considering the study limitations including heterogeneity and retrospective nature of the primary data, the conclusions should be interpreted with caution.     

The inflammation-related biomarker CXCR7 independently predicts patient outcome after radical prostatectomy

IntroductionThe influence of inflammation on prostate tumor carcinogenesis is currently much better known than with its role in prostate cancer (CaP) progression. We evaluated the prognostic value of epigenetic (HDAC1, HDAC4, H3Ac) and inflammation-related (CXCR4, CXCR7, CXCL12) biomarkers immunoexpression, in radical prostatectomy specimens, from 2 cohorts of CaP patients with long term follow-up.Materials and MethodsFormalin-fixed and paraffin-embedded radical prostatectomy specimens were obtained from the pathology archives of Prof. Doutor Fernando Fonseca Hospital, in Amadora, Portugal and Portuguese Oncology Institute of Porto, in Porto, Portugal, and tissue microarrays were assembled. It was achieved a set of 234 patients submitted to radical retropubic prostatectomy between January 2000 and December 2005. Immunohistochemistry was used for evaluation of protein expression of epigenetic and inflammation-related markers. Nuclear staining was assessed using digital image analysis. Study outcomes included disease-specific survival and disease-free survival (DFS). Statistical analysis was tabulated using SPSS version 23.0. Hazard ratios (HRs) and survival curves were estimated using Cox-regression and Kaplan-Meyer models, respectively. Statistical significance was set at P < 0.05.ResultsComplete follow-up data was available for 234 patients and median follow-up time was 164 [11–218] months. Patients with higher CXCR4 immunoexpression experienced significantly worse disease-specific survival compared to patients with low expression (HR = 1.016, 95% CI: 1.002–1.031). The same happened with CXCL12 (HR = 0.546 95% CI: 0.322–0.926) and H3Ac (HR = 1.015, 95% CI: 1.001c1.029). In what concerns to DFS, patients with higher expression of CXCR4 and CXCR7 were significantly more prone to experience disease recurrence (HR = 1.003, 95% CI: 1.000–1.005 and HR = 1.111, 95% CI:1.032–1.196, respectively). When adjusted to pTStage and WHO Grade Groups, CXCR7 maintained independent impact on DFS (HR = 1.119, 95% CI: 1.032–1.214).ConclusionsThe interplay between inflammation and epigenetics and its impact in CaP outcome deserves further studies in the future. CXCR7 shows an independent predictor for worse DFS after radical prostatectomy, and could provide important prognostic information for patient management after radical prostatectomy.     

Smoking status and pathological response to neoadjuvant chemotherapy among patients with bladder cancer: a pooled analysis

BackgroundSmoking status has been confirmed as an independent prognostic factor for bladder cancer. However, for patients who received neoadjuvant chemotherapy (NAC), the influence of smoking status on the pathological response and prognosis remains unclear. This pooled analysis aimed to investigate whether smoking status is an independent risk factor for pathological response, recurrence, and prognosis in patients with bladder cancer who undergo NAC.MethodsWe searched PubMed, Web of Science, Embase, Cochrane Library, and Google Scholar for related studies published between 1990 and 2017. In total, 10 studies comprising 1,382 patients with muscle-invasive bladder cancer were included. The odds ratio (OR) and 95% confidence interval (CI) of complete pathological response, partial pathological response, overall survive (OS), recurrence, and cancer-specific mortality (CSM) were chosen as outcome measures. Analyses were performed using Review Manager (version 5.3, The Cochrane Collaboration, UK) and Stata statistical software (version 15, Stata Corp., USA).ResultsCompared to nonsmokers, smokers were less likely to have a complete pathologic response (OR =0.55, 95% CI: 0.35–0.87) and partial pathological response (OR =0.57, 95% CI: 0.37–0.88). However, we found no significant association between smoking status and overall survival (OR =0.71, 95% CI: 0.28–1.80), recurrence (OR =1.35, 95% CI: 0.97–1.88), and cancer-specific mortality (OR =0.90, 95% CI: 0.62–1.32).ConclusionsSmoking reduces both complete and partial pathological response rate to NAC in patients with bladder cancer. Thus, smoking status should be given more importance when developing treatment plans and evaluating efficacy, particularly of NAC, among bladder cancer patients.     

Post-operative abdominal complications in Crohn's disease in the biological era: Systematic review and meta-analysis

AIM: To perform a systematic review and meta-analysis on post-operative complications after surgery for Crohn's disease(CD) comparing biological with no therapy.METHODS: Pub Med, Medline and Embase databases were searched to identify studies comparing postoperative outcomes in CD patients receiving biological therapy and those who did not. A meta-analysis with a random-effects model was used to calculate pooled odds ratios(OR) and confidence intervals(CI) for each outcome measure of interest. RESULTS: A total of 14 studies were included for metaanalysis, comprising a total of 5425 patients with CD 1024(biological treatment, 4401 control group). After biological therapy there was an increased risk of total infectious complications(OR = 1.52; 95%CI: 1.14-2.03, 8 studies) and wound infection(OR = 1.73; 95%CI: 1.12-2.67; P = 0.01, 7 studies). There was no increased risk for other complications including anastomotic leak(OR = 1.19; 95%CI: 0.82-1.71; P = 0.26), abdominal sepsis(OR = 1.22; 95%CI: 0.87-1.72; P = 0.25) and re-operation(OR = 1.12; 95%CI: 0.81-1.54; P = 0.46) in patients receiving biological therapy. CONCLUSION: Pre-operative use of anti-TNF-α therapy may increase risk of post-operative infectious complications after surgery for CD and in particular wound related infections.