Effect of Preoperative Double-J Ureteral Stenting before Flexible Ureterorenoscopy on Stone-free Rates and Complications.

The effect of preoperative Double-J (DJ) ureteral stenting before flexible ureterorenoscopy (FURS) in the treatment for urinary stones was evaluated. We retrospectively enrolled 306 consecutive patients who underwent FURS from Jan. 2014 to Dec. 2017. All the patients were classified into two groups according to whether they had DJ ureteral stenting before FURS. Baseline characteristics (age, sex, stone location, stone size, surgical success rate, operation time, stone-free rate of the first day after surgery, stone-free rate of the first month after surgery, total complication rate) were compared using Chi-square test for categorical variables and Kruskal-Wallis test for continuous variables. In total, 306 patients were included in this study. The group of DJ stenting before FURS included 203 (66.3%) patients, and non-DJ stenting before FURS was observed in 103 (33.7%) patients. The group of DJ stenting before FURS was significantly associated with a shorter operation time (53.8 vs. 59.3 min, P<0.001), a higher stone-free rate of the first day after surgery (69.0% vs. 51.5%, P=0.003). However, statistical significant differences were not found in the age, sex, stone location, stone size, surgical success rate, stone-free rate of the first month after surgery (89.2% vs. 81.6%, P=0.065) and total complication rate (5.4% vs. 9.7%, P=0.161) between the two groups. Preoperative DJ ureteral stenting before FURS could reduce the operation time and increase stone-free rate of the first day after surgery. However, it might not benefit the stone-free rate of the first month after surgery and reduce the complication rate. Preoperative DJ stenting should be not routinely performed.

Effects of diabetes mellitus and Metformin administration on prostate cancer detection at biopsy among Chinese men: a case-control study.

PURPOSE: To determine the associations among diabetes status, Metformin administration and prostate cancer (PCa) detection at biopsy in Chinese population. METHODS: A case-control study was conducted among a prospectively enrolled prostate biopsy cohort of 518 patients from Jan 2013 to Dec 2014 at our institute. Diabetes status and Metformin administration were determined through medical records and self-report. Different clinical characteristics were registered and compared among different groups. Univariate and multivariate logistic regression analyses were performed to evaluate the effects of diabetes status and Metformin administration on the detection of overall as well as high-grade PCa at biopsy. RESULTS: PCa was detected in 229 (44.2%) men, and high-grade PCa (Gleason score ≥8) was detected in 65 (12.5%) men. Diabetes was observed in 96 men, and 28 of them were administered with Metformin. Both overall and high-grade cancer detection rates were significantly higher in diabetic patients (p<0.001). In multivariate analysis, diabetes status was a risk factor for high-grade cancer detection (OR 7.699, 95%CI 3.483-17.020, p<0.001), but not for total PCa detection (OR 1.774, 95%CI 0.831-3.787, p=0.138). Meanwhile, Metformin administration was proved to be a protective factor for high-grade disease (OR 0.420, 95%CI 0.201-0.879, p=0.021) in multivariate analysis, while no correlation was detected with overall cancer detection (OR 0.786, 95%CI 0.172-3.593, p=0.756). CONCLUSIONS: Diabetes status was positively associated with biopsy-mediated high-grade PCa detection in Chinese population, while the positive association would be partly compromised by Metformin administration.

Differential expressions of integrin-linked kinase, ß-parvin and cofilin 1 in high-fat diet induced prostate cancer progression in a transgenic mouse model.

High-fat diet induced obesity was associated with more aggressive prostate cancer. Recent research has demonstrated that integrin-linked kinase (ILK), ß-parvin and downstream cofilin 1 jointly affected cancer progression. Meanwhile, these proteins were also involved in energy metabolism. Therefore, the present study was conducted to investigate the potential function of ILK, ß-parvin and cofilin 1 in the high-fat diet-induced progression of prostate cancer. Transgenic mice with prostate cancer were employed, fed with different diets and sacrificed at 20 and 28 weeks. Tumor differentiation, extracapsular extension and metastasis were compared between the groups. Expression levels of ILK, ß-parvin and cofilin 1 in prostate were evaluated by immunohistochemical analysis and determined by an immunoreactivity score. Public databases were applied for analysis and validation. It was detected that high-fat diet feeding promoted cancer progression in transgenic mice with prostate cancer, with increased expressions of ß-parvin (P=0.038) and cofilin 1 (P=0.018). Higher expressions of ILK, ß-parvin and cofilin 1 were also associated with poorer cancer differentiation. Additionally, higher mRNA levels of CFL1 were correlated with a worse disease-free survival in patients of certain subgroups from The Cancer Genome Atlas database. Further studies were warranted in discussing the potential roles of ILK, ß-parvin and cofilin 1 in high-fat diet feeding induced progression of prostate cancer.

High-fat diet-induced adipokine and cytokine alterations promote the progression of prostate cancer in vivo and in vitro.

High-fat diet (HFD) -induced obesity is associated with more aggressive and lethal prostate cancer (PCa) in males, although the exact underlying mechanisms remain unclear. In the present study, transgenic adenocarcinoma of mouse prostate (TRAMP) models fed on an HFD (40% fat) or a control diet (CD; 16% fat) were generated, and cancer differentiation, local invasion and metastasis were compared at 20, 24 and 28 weeks. Mouse sera from each group were collected, and adipokines and cytokines were measured using multiplex immunoassays. HFD-sera and CD-sera were additionally processed into conditioned media (2.5% mixed sera), and in vitro studies were conducted to determine the proliferation, migration and invasion of cancer cells when conditioned media were used for culture. In TRAMP mice, HFD feeding increased body weight and adipose tissue deposition, and promoted the progression of PCa, specifically with regard to poorer differentiation, increased local invasion and metastasis rate. Sera from HFD-fed TRAMP mice contained increased levels of leptin, and a time-dependent increasing trend in the levels of CC chemokine ligand (CCL)3, CCL4, CCL5 and CXC chemokine ligand (CXCL)10 was observed. However, no alterations were detected in the levels of adiponectin, interleukin (IL)-4, IL-5, IL-6, IL-12p70, interferon-γ, tumor necrosis factor-α, CCL2, CCL7, CCL11, CXCL1 and CXCL2. In vitro studies determined that HFD-sera-conditioned medium promoted proliferation, migration and invasion of DU145 cells, as compared with CD-sera-conditioned medium and serum-free medium. In conclusion, the results of the present study suggested that the circulating adipokine and cytokine alterations in response to excess adipose tissue deposition induced by HFD feeding contributed to PCa progression.

Prognostic factors in Chinese patients with prostate cancer receiving primary androgen deprivation therapy: validation of Japan Cancer of the Prostate Risk Assessment (J-CAPRA) score and impacts of pre-existing obesity and diabetes mellitus.

PURPOSE: Our aim was to determine the prognostic factors in Chinese patients with prostate cancer receiving primary androgen deprivation therapy (PADT), validate the Japan Cancer of the Prostate Risk Assessment (J-CAPRA) score, and investigate the impacts of pre-existing obesity and diabetes mellitus (DM). METHODS: The study enrolled Chinese patients diagnosed with prostatic adenocarcinoma and treated with bilateral orchiectomy as PADT at Huashan Hospital, Fudan University (Shanghai, China), from January 2003 to December 2015. The overall survival (OS) and prognostic value of J-CAPRA score, pre-existing obesity, DM, and various clinicopathological variables were analyzed. RESULTS: Of the 435 patients enrolled, 174 (40.0%) deaths occurred during follow-up; 3- and 5-year OS were 74.0 and 58.9%, respectively. Multivariate analysis identified that higher Gleason score and metastasis were both correlated with worse OS and that higher J-CAPRA score was correlated with worse OS [hazard ratio (HR) 1.110, 95% confidence interval (CI) 1.035-1.190, P = 0.003). Different risk categories based on J-CAPRA score showed good stratification in OS (log-rank P = 0.015). In subgroup analysis, pre-existing obesity as a protective factor in younger patients (age ≤ 65, HR 0.271, 95% CI 0.075-0.980, P = 0.046) and pre-existing DM as a risk factor in older patients (> 75, HR 1.854, 95% CI 1.026-3.351, P = 0.041) for OS were recognized, and the prediction accuracy of J-CAPRA was elevated after incorporating pre-existing obesity and DM. CONCLUSIONS: The J-CAPRA score presented with good OS differentiation among Chinese patients under PADT. Younger patients (age ≤ 65) had better OS with pre-existing obesity, while older patients (age > 75) had worse OS with pre-existing DM.

Genetic polymorphisms in leptin, adiponectin and their receptors affect risk and aggressiveness of prostate cancer: evidence from a meta-analysis and pooled-review.

Leptin and adiponectin signaling was associated with development and progression of various cancers. The present study aimed to clarify the role of genetic variants in leptin, adiponectin and their receptors in prostate cancer. After comprehensive search and manuscript scanning, a total of 49 genetic variants were enrolled and examined for their relations to cancer risk and aggressiveness. In the meta-analysis, LEP rs7799039 (allele contrast: OR 1.133, 95%CI 1.024-1.254), ADIPOQ rs2241766 (allele contrast: OR 1.201, 95%CI 1.015-1.422) and ADIPOR1 rs10920531 (allele contrast: OR 1.184, 95%CI 1.075-1.305) variants were identified to be correlated with increased risk of prostate cancer. On the contrary, LEPR rs1137101 (allele contrast: OR 0.843, 95%CI 0.730-0.973) and ADIPOR1 rs2232853 (allele contrast: OR 0.638, 95%CI 0.535-0.760) variants were associated with decreased risk of prostate cancer. From the pooled-review, we additionally recognized eight variants associated with cancer risk and another eight variants associated with cancer aggressiveness, respectively. These observations indicated important roles of leptin, adiponectin and their receptors in the development and progression of prostate cancer. The identified polymorphisms might assist in developing better risk-assessment tools, as well as generating novel targeted therapies, especially for obese cancer patients with impaired leptin and adiponectin signaling.

The Huashan risk calculators performed better in prediction of prostate cancer in Chinese population: a training study followed by a validation study.

The performances of the Prostate Cancer Prevention Trial (PCPT) risk calculator and other risk calculators for prostate cancer (PCa) prediction in Chinese populations were poorly understood. We performed this study to build risk calculators (Huashan risk calculators) based on Chinese population and validated the performance of prostate-specific antigen (PSA), PCPT risk calculator, and Huashan risk calculators in a validation cohort. We built Huashan risk calculators based on data from 1059 men who underwent initial prostate biopsy from January 2006 to December 2010 in a training cohort. Then, we validated the performance of PSA, PCPT risk calculator, and Huashan risk calculators in an observational validation study from January 2011 to December 2014. All necessary clinical information were collected before the biopsy. The results showed that Huashan risk calculators 1 and 2 outperformed the PCPT risk calculator for predicting PCa in both entire training cohort and stratified population (with PSA from 2.0 ng ml-1 to 20.0 ng m). In the validation study, Huashan risk calculator 1 still outperformed the PCPT risk calculator in the entire validation cohort (0.849 vs 0.779 in area under the receiver operating characteristic curve [AUC] and stratified population. A considerable reduction of unnecessary biopsies (approximately 30%) was also observed when the Huashan risk calculators were used. Thus, we believe that the Huashan risk calculators (especially Huashan risk calculator 1) may have added value for predicting PCa in Chinese population. However, these results still needed further evaluation in larger populations.

Body mass index is associated with higher Gleason score and biochemical recurrence risk following radical prostatectomy in Chinese men: a retrospective cohort study and meta-analysis.

BACKGROUND: The aim of the study is to investigate whether body mass index (BMI) affected pathological characteristics and biochemical recurrence (BCR) of prostate cancer after radical prostatectomy in Chinese men. METHODS: Medical records of 211 Chinese patients who underwent radical prostatectomy between 2006 and 2014 were retrospectively reviewed, with follow-up time of 24.5 ± 27.0 months. Multivariate logistic and Cox regression analyses were applied to address the impact of BMI on adverse pathological outcomes and BCR following prostatectomy. A meta-analysis of published studies from MEDLINE or EMBASE was conducted to determine the relationship between BMI and BCR following prostatectomy among Asian populations. RESULTS: Higher BMI was positively correlated with higher biopsy Gleason score (odds ratios (OR) 1.163, 95 % confidence interval (CI) 1.023-1.322, P = 0.021) and pathological Gleason score (OR 1.220, 95 % CI 1.056-1.410, P = 0.007) in multivariate analysis. BCR was detected in 48 patients (22.7 %). Multivariate Cox proportional hazards analysis revealed that higher BMI (hazard ratio (HR) 1.145, 95 % CI 1.029-1.273, P = 0.013) and prostate-specific antigen (HR 1.659, 95 % CI 1.102-2.497, P = 0.015) levels were independent predictors of BCR. The meta-analysis enrolled eight Asian studies of 4145 patients treated by radical prostatectomy. Based on random-effects approach, a 5 kg/m(2) increase in BMI was correlated with 28 % higher risk of BCR (HR 1.22, 95 % CI 0.86-1.72) without statistical significance. CONCLUSIONS: The present study suggested that higher BMI was an independent risk factor for a higher Gleason score, as well as an independent predictor of BCR after radical prostatectomy in Chinese patients. Meta-analysis of Asian studies also indicated that obese patients, although without statistical significance, might be more likely to suffer from BCR.

Higher body mass index increases the risk for biopsy-mediated detection of prostate cancer in Chinese men.

OBJECTIVE: To investigate the relationship between body mass index (BMI) and prostate cancer (PCa) risk at biopsy in Chinese men. PATIENTS AND METHODS: We retrospectively reviewed the records of 1,807 consecutive men who underwent initial multicore (≥10) prostate biopsy under transrectal ultrasound guidance between Dec 2004 and Feb 2014. BMI was categorised based on the Asian classification of obesity as follows: <18.5 (underweight), 18.5-22.9 (normal weight), 23-24.9 (overweight), 25-29.9 (moderately obese), and ≥30 kg/m2 (severely obese). The odds ratios (OR) of each BMI category for risk of PCa and high-grade prostate cancer (HGPCa, Gleason score ≥4+3) detection were estimated in crude, age-adjusted and multivariate-adjusted models. Prevalence ratios and accuracies of PSA predicted PCa were also estimated across BMI groups. RESULTS: In total, PCa was detected by biopsy in 750 (45.4%) men, and HGPCa was detected in 419 (25.4%) men. Compared with men of normal weight, underweight men and obese men were older and had higher prostate specific antigen levels. The risk of overall PCa detection via biopsy presented an obvious U-shaped relationship with BMI in crude analysis. Overall, 50.0%, 37.4%, 45.6% 54.4% and 74.1% of the men in the underweight, normal weight, overweight, moderately obese and severely obese groups, respectively, were diagnosed with PCa via biopsy. In multivariate analysis, obesity was significantly correlated with a higher risk of PCa detection (OR = 1.17, 95%CI 1.10-1.25, P<0.001). However, higher BMI was not correlated with HGPCa detection (OR = 1.03, 95%CI 0.97-1.09, P = 0.29). There were no significant differences in the accuracy of using PSA to predict PCa or HGPCa detection across different BMI categories. CONCLUSION: Obesity was associated with higher risk of PCa detection in the present Chinese biopsy population. No significant association was detected between obesity and HGPCa.

Proinflammatory cytokines in prostate cancer development and progression promoted by high-fat diet.

BACKGROUND: We aimed to examine whether proinflammatory cytokines participated in prostate cancer (PCa) development and progression promoted by high-fat diet (HFD). METHODS: TRAMP (transgenic adenocarcinoma mouse prostate) mice were randomly divided into two groups: normal diet group and HFD group. Mortality rate and tumor formation rate were examined. TRAMP mice were sacrificed and sampled on the 20th, 24th, and 28th week, respectively. Levels of proinflammatory cytokines, including IL-1α, IL-1ß, IL-6, and TNF-α, were tested by FlowCytomix. Prostate tissue of TRAMP mice was used for histology study. RESULTS: A total of 13 deaths of TRAMP mice were observed, among which 3 (8.33%) were from the normal diet group and 10 (27.78%) from the HFD group. The mortality rate of TRAMP mice from HFD group was significantly higher than that of normal diet group (P = 0.032). Tumor formation rate at 20th week of age of HFD group was significantly higher than that of normal diet group (P = 0.045). Proinflammatory cytokines levels, including IL-1α, IL-1ß, IL-6, and TNF-α, were significantly higher in HFD TRAMP mice. CONCLUSIONS: HFD could promote TRAMP mouse PCa development and progression with elevated proinflammatory cytokines levels. Proinflammatory cytokines could contribute to PCa development and progression promoted by HFD.

Obesity affects the biopsy-mediated detection of prostate cancer, particularly high-grade prostate cancer: a dose-response meta-analysis of 29,464 patients.

BACKGROUND AND OBJECTIVES: In previous studies, obesity (measured according to the body mass index) has correlated inconsistently with the risk of biopsy-measured prostate cancer, and specifically high-grade prostate cancer. This meta-analysis aimed to clarify these correlations. METHODS: A comprehensive literature search of the MEDLINE and EMBASE databases was conducted for relevant studies published through January 2014. The pooled estimates of odds ratios (OR) and confidence intervals (CI) were computed, and the meta-analysis was performed with the STATA software according to a random effects approach. RESULTS: A total of 11 studies that included 29,464 individuals were identified. A 5-kg/m2 increase in body mass index was associated with a 15% (OR, 1.15; 95% CI, 0.98-1.34) higher risk of prostate cancer detection and a 37% (OR, 1.37; 95% CI, 1.19-1.57) higher risk of high-grade prostate cancer detection at biopsy. There were no differences among the results of studies conducted in the USA, Europe or Asia. We also found that studies that had adjusted for prostate-specific antigen levels, digital rectal examination results, and prostate volumes obtained positive significant outcomes (OR, 1.27; 95% CI, 1.12-1.44), whereas studies that did not adjust for the above-mentioned confounding variables obtained negative results (OR, 0.92; 95% CI, 0.68-1.25). Moreover, the positive correlation between body mass index and the detection of both prostate cancer and high-grade diseases tended to be stronger as the number of biopsy cores increased. CONCLUSION: The present meta-analysis demonstrated that a high body mass index correlated positively with prostate cancer detection, especially high-grade prostate cancer detection. The adoption of a modified and possibly more aggressive biopsy strategy was suggested for obese populations.

Will metformin postpone high-fat diet promotion of TRAMP mouse prostate cancer development and progression?

PURPOSE: We aimed to examine the effect of high-fat diet (HFD) on prostate cancer (PCa) development and progression and to investigate whether metformin would postpone PCa development and progression promoted by HFD. METHODS: TRAMP mice were randomly divided into three groups: normal diet group, HFD group and metformin-HFD (Met-HFD) group. Mortality rate and tumor formation rate were examined. TRAMP mice were sacrificed and sampled on the 20th, 24(th), and 28th week, respectively. Serum levels of insulin and IGF-1 were tested by ELISA. Prostate tissue of TRAMP mice was used for HE staining. RESULTS: A total of 17 deaths of TRAMP mice were observed, including 3 (10 %) from the normal diet group, 10 (33.33 %) from the HFD group, and 4 (13.33 %) from Met-HFD group. The mortality rate of TRAMP mice from HFD group was significantly higher than that of normal diet group (P = 0.028), and metformin could moderately decrease the mortality rate by 60.01 % (P = 0.067). Tumor formation rates were not significantly different among the three groups. Levels of glucose, insulin, and IGF-1 tended to increase with TRAMP mice's age in HFD group. TRAMP mice from HFD group had higher serum insulin and IGF-1 levels. A moderate decrease in IGF-1 was also seen in Met-HFD group. CONCLUSIONS: HFD could promote TRAMP mouse PCa development and progression and metformin had moderate effect of reducing PCa mortality rate with a decrease in serum IGF-1 level.

Obesity has multifaceted impact on biochemical recurrence of prostate cancer: a dose-response meta-analysis of 36,927 patients.

Obesity is inconsistently related to biochemical recurrence (BCR) of prostate cancer (PCa) in different epidemiological studies. We conducted a systematic review and dose-response meta-analysis of published studies from MEDLINE and EMBASE in order to determine the relationship between body mass index (BMI) and BCR of PCa. We identified a total of 26 studies including 36,927 individuals. Pooled estimates of relative risk (RR) and confidence interval (CI) were computed, and dose-response meta-analysis was subsequently performed. Based on the random-effects approach, a 5 kg/m(2) increase in BMI was associated with 16 % (RR 1.16, 95 % CI 1.08-1.24) higher risk of BCR for entire set of 26 studies. Significantly higher rates of BCR were also observed in radical prostatectomy series (RR 1.17, 95 % CI 1.07-1.28) and external beam radiation therapy series (RR 1.19, 95 % CI 1.10-1.28), while no significant correlation was observed in brachytherapy series (RR 0.91, 95 % CI 0.64-1.28). Different BCR outcomes came out for studies held in USA (RR 1.18, 95 % CI 1.10-1.28), Europe (RR 1.04 95 % CI 0.91-1.17) and Asia (RR 1.83 95 % CI 0.85-3.97), respectively. There was limited evidence of a nonlinear association between BMI and BCR, which showed a critical point of 33 in BMI. The findings from meta-analysis showed that excess BMI was positively correlated with BCR of PCa multifacetedly, indicating good weight control and detailed attention to treating obese patients might improve the prognosis of PCa.