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.

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.

Crosstalk between apoptosis and autophagy in prostate epithelial cells under androgen deprivation.

The present study investigated the molecular mechanism of apoptosis and autophagy in prostate epithelial cells under androgen deprivation (AD). BPH-1 cells were divided into four groups as follows: Control (Cont), AD, autophagy inhibition (AI) and AD + AI groups. Cells in the four groups were treated accordingly, and the level of apoptosis was subsequently measured via flow cytometry. The expression of the microtubule-associated proteins 1A/1B light chain 3 (LC3), caspase-3, poly (ADP-ribose) polymerase 1 (PARP-1) and Beclin-1 proteins of BPH-1 cells was detected at different time points following culture in androgen-deprived medium. Western blotting revealed that the basal levels of the LC3-II protein were detected at 0 h. At 4 h, LC3-II was significantly increased compared with 0 h (P<0.05). Beginning at 20 h, the expression level of the LC3-II protein decreased significantly (P<0.05). Western blotting revealed that beginning at 24 h, the expression level of the PARP-1 protein decreased significantly (P<0.001) and the cleavage fragments of the PARP-1 protein appeared. These results further imply that autophagy serves a cell protective function by mutual inhibition with apoptosis in BPH-1 cells in the removal of androgen conditions. Furthermore, the fragments of the cleaved Beclin-1 protein appeared as 35 and 37 kDa bands. Flow cytometry analysis demonstrated that the rate of cell apoptosis in the AD, AI and AD + AI groups was significantly increased compared with the Cont group (P<0.01). Compared with the AD or the AI groups individually, the rate of cell apoptosis in the AD + AI group was significantly increased (P<0.001). These findings suggest that in the early stage of AD, autophagy has a compensatory function in the cell, whereas in the whole process, autophagy and apoptosis share a mutual antagonism. The Beclin-1-C protein fragment contributed positive feedback to the process of apoptosis, which may be a potential mechanism of AD therapy. Therefore, AD and AI exhibit a synergistic effect to further improve the level of apoptosis.

Roles of autophagy in androgen-induced benign prostatic hyperplasia in castrated rats.

The present study investigated the role of androgen in the process of androgen-induced prostate hyperplasia in castrated rats and assessed the role of the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/Akt/mTOR) pathway in this process. Furthermore, the extent to which autophagy may affect the level of androgen-induced benign prostatic hyperplasia was also explored. A total of 40 Sprague Dawley rats were randomly divided into four groups: Testosterone group, rapamycin group, 3-methyladenine (3-MA) group, and control group. The extent of hyperplasia in prostate tissue the apoptosis and autophagy were assayed. The prostate wet weight, volume and index in the testosterone group were significantly higher compared with the control group (P<0.05) and these factors were significantly lower in the rapamycin group compared with the testosterone group (P<0.05). HE staining demonstrated that prostate hyperplasia was obvious in the testosterone group. Western blotting revealed that caspase-3 levels were higher in the 3-MA group compared with the control group and Bcl-2 was higher in the testosterone group compared with the control group (P<0.05). Furthermore, in the rapamycin group, Bcl-2 protein expression levels were significantly lower than those in the testosterone group (P<0.05). The prostate tissue was analyzed using electron microscopy and autophagy bodies were identified in the rapamycin group. In the process of androgen-induced prostatic hyperplasia in castrated rats, the role of androgen may be related to the PI3K/Akt/mTOR signaling pathway. Rapamycin was able to inhibit the effect of testosterone and promoted prostate tissue hyperplasia by inhibiting the PI3K/Akt pathway. In addition to inhibiting apoptosis in prostate cells, androgen was able to induce rat prostate hyperplasia and may also be related to the promotion of the proliferation of prostate cells.

Clinical efficacy of digital flexible reteroscope and modular flexible ureteroscope combined with holmium laser lithotripsy for subrenal calyx calculus / 中国内镜杂志

Objective To evaluate the efficacy of flexible ureteroscopy combined with holmium laser lithotripsy for the treatment of subrenal calyx calculus, and comparing with digital flexible ureteroscope and modular flexible ureteroscope with holmium lithotripsy for the difference of the efficacy of the treatment of subrenal calyx calculus. Methods Review of the clinical data of 93 patients with subrenal calyx calculus, of which 48 cases were treated with digital flexible ureteroscope (digital flexible ureteroscope group, DFU group), 45 cases with modular flexible ureteroscope treatment (modular flexible ureteroscope group, MFU group), lithotripsy effect and complications were compared between the two groups. Results The mean operation time, one-session stone-free rate were significantly different between the two groups (P < 0.05). No significant differences in hospital stay, the success rate of looking for calculus, complication and hospitalization expense (P > 0.05). Conclusion With digital flexible ureteroscope and modular flexible ureteroscope treatment of subrenal calyx calculus all are safe and effective. The use of DFU than the use of MFU in the treatment of subrenal calyx calculus operation time is shorter, stone-free rateis higher, the effect is better. There is little difference between their hospitalization expenses, but the use of MFU can reduce the cost of the department.

Clinical efficacy of digital flexible reteroscope and modular flexible ureteroscope combined with holmium laser lithotripsy for subrenal calyx calculus / 中国内镜杂志

Objective To evaluate the efficacy of flexible ureteroscopy combined with holmium laser lithotripsy for the treatment of subrenal calyx calculus, and comparing with digital flexible ureteroscope and modular flexible ureteroscope with holmium lithotripsy for the difference of the efficacy of the treatment of subrenal calyx calculus. Methods Review of the clinical data of 93 patients with subrenal calyx calculus, of which 48 cases were treated with digital flexible ureteroscope (digital flexible ureteroscope group, DFU group), 45 cases with modular flexible ureteroscope treatment (modular flexible ureteroscope group, MFU group), lithotripsy effect and complications were compared between the two groups. Results The mean operation time, one-session stone-free rate were significantly different between the two groups (P < 0.05). No significant differences in hospital stay, the success rate of looking for calculus, complication and hospitalization expense (P > 0.05). Conclusion With digital flexible ureteroscope and modular flexible ureteroscope treatment of subrenal calyx calculus all are safe and effective. The use of DFU than the use of MFU in the treatment of subrenal calyx calculus operation time is shorter, stone-free rateis higher, the effect is better. There is little difference between their hospitalization expenses, but the use of MFU can reduce the cost of the department.

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.

The influence of prostate volume on cancer detection in the Chinese population.

In western populations, prostate volume (PV) has been proven to be one of the strongest predictors of detecting prostate cancer (PCa) in biopsies. We performed this study in a biopsy cohort, to evaluate associations among the prostate volume, prostate-specific antigen (PSA) and PCa detection in the Chinese population. Between the years, 2007-13, 1486 men underwent prostate biopsy at Huashan Hospital, Fudan University, Shanghai, China. The study population was divided into two groups for analysis according to total PSA (tPSA) range (4 ng ml-1 < tPSA ≤ 20 ng ml-1 and tPSA > 20 ng ml-1 ). PV, age, tPSA, digital rectal examination (DRE) and transrectal ultrasound (TRUS) results were also included in the analysis. Although the positive biopsy rates decreased in both tPSA range groups, the downtrend was more pronounced in the 4 ng ml-1 < tPSA ≤ 20 ng ml-1 group; therefore, we focused on 853 men in this group with increasing PV. In multivariate logistic regression analysis, only DRE was found to be associated with PCa in four PV groups (P < 0.05) and tPSA did not show a good predictive ability when PV exceeded 50 ml (P > 0.05). Further, it may suggest that with increasing PV, the cancer detection rate decreased in men with different tPSA, DRE and TRUS nodule statuses (all P values for trends were <0.001). Our study indicates that in tPSA ranging from 4 to 20 ng ml-1 , the use of PV ranges of 0-35 ml, 35-50 ml and > 50 ml might be taken into consideration for the biopsy decision-making in the Chinese population.

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.