The impact of catheter removal time on urinary continence and overactive bladder symptoms after robot-assisted radical prostatectomy: a retrospective analysis of consecutive 432 cases from a single institution.

Background: After radical prostatectomy, the optimal length of postoperative catheterization time remains to be determined. This study investigates the impact of catheter removal time on urinary continence and overactive bladder (OAB) symptoms after robot-assisted radical prostatectomy (RARP). Methods: Four hundred and thirty-two consecutive patients underwent RARP by a single surgeon between Nov 2020 and Oct 2021. Time to catheter removal was categorized into 7, 10, and ≥14 days. Continence was defined as no more than 1 pad used or no more than 20 g of urine leakage per 24 hours. The patients' continence rates and overactive bladder symptom score (OABSS) were assessed at 48 hours, 1 week, 4, 12, and 24 weeks after catheter removal. Results: Overall, continence rates were 37.3% 48 hours after catheter removal, 54.4% 1 week, 77.5% 4 weeks, 92.1% 12 weeks, and 97.9% 24 weeks after catheter removal. The median time to regain continence was 1 week. At 4 weeks after catheter removal, the continence rate in the ≥14 days group (70.5%) was significantly lower than the 7 days group (86.3%) and 10 days group (83.0%) (P=0.001). In a univariate Cox regression analysis, the presence of diabetes, higher pre-operative OABSS, and a catheterization time of 10 days were associated with worse continence recovery. The mean OABSS of patients in the continent group were significantly lower than the incontinent group at 48 hours, 4, 12 and 24 weeks after catheter removal. At 24 weeks after catheter removal, the mean OABSS in the 7 days group was significantly lower than in other groups. Conclusions: Early catheter removal (7 days) was associated with better continence results and lower OABSS at 4 and 24 weeks after catheter removal respectively.

Estrogen and G protein-coupled estrogen receptor accelerate the progression of benign prostatic hyperplasia by inducing prostatic fibrosis.

Benign prostatic hyperplasia (BPH) is the most common and progressive urological disease in elderly men worldwide. Epidemiological studies have suggested that the speed of disease progression varies among individuals, while the pathophysiological mechanisms of accelerated clinical progression in some BPH patients remain to be elucidated. In this study, we defined patients with BPH as belonging to the accelerated progressive group (transurethral resection of the prostate [TURP] surgery at ≤50 years old), normal-speed progressive group (TURP surgery at ≥70 years old), or non-progressive group (age ≤50 years old without BPH-related surgery). We enrolled prostate specimens from the three groups of patients and compared these tissues to determine the histopathological characteristics and molecular mechanisms underlying BPH patients with accelerated progression. We found that the main histopathological characteristics of accelerated progressive BPH tissues were increased stromal components and prostatic fibrosis, which were accompanied by higher myofibroblast accumulation and collagen deposition. Mechanism dissection demonstrated that these accelerated progressive BPH tissues have higher expression of the CYP19 and G protein-coupled estrogen receptor (GPER) with higher estrogen biosynthesis. Estrogen functions via GPER/Gαi signaling to modulate the EGFR/ERK and HIF-1α/TGF-ß1 signaling to increase prostatic stromal cell proliferation and prostatic stromal fibrosis. The increased stromal components and prostatic fibrosis may accelerate the clinical progression of BPH. Targeting this newly identified CYP19/estrogen/GPER/Gαi signaling axis may facilitate the development of novel personalized therapeutics to better suppress the progression of BPH.

Icariin attenuates renal fibrosis in vivo and in vitro by inhibiting the Notch2/Hes-1 pathway.

Chinese herbs were widely proposed as a novel approach for renal fibrosis. Icariin has been reported to be involved in a variety of diseases. Unilateral ureteral obstruction (UUO) is a popular experimental model of renal injury, which is often used in the study of renal fibrosis. A UUO mouse model was successfully constructed, and tubular injury and renal fibrosis were observed. Icariin treatment attenuated tubular injury and renal fibrosis in UUO mice. In addition, treatment with Icariin reduced the fibronectin, type I collagen and α-SMA levels in UUO mice. Furthermore, in a transforming growth factor (TGF)-ß1-induced renal fibrosis cell model, icariin treatment also decreased fibronectin, type I collagen and α-SMA expression. Icariin treatment also reversed the enhanced migration of TGF-ß1-induced HK-2 cells. These data indicated that icariin suppressed renal fibrosis in vivo and in vitro. Additionally, icariin treatment suppressed the Notch2/Hes-1 pathway in UUO mice and TGF-ß1-treated HK-2 cells. In summary, this study found that icariin reduced renal fibrosis in vivo and in vitro by inhibiting the Notch2/Hes-1 pathway, which might help to improve therapies for renal fibrosis.

Immune characteristics of renal allograft donors with mesangial IgA deposition.

BACKGROUND: There are few studies describing the prevalence and immune features of people with subclinical mesangial immunoglobulin A (IgA) deposition in the Chinese population. We sought to investigate the prevalence of mesangial IgA deposition among kidney donors and the immune characteristics of donors with mesangial IgA deposition. METHODS: Fifty blood-related living donors with zero-hour allograft biopsies obtained at Peking University First Hospital were enrolled. Galactose-deficient IgA1 (Gd-IgA1) in glomerular deposits was examined by double immunofluorescent staining using the specific monoclonal antibody KM55. Plasma IgA, IgA1, Gd-IgA1 and antibodies directed against Gd-IgA1 were measured using enzyme-linked immunosorbent assay. RESULTS: Thirteen of 50 (26%) donors had mesangial IgA deposition, which was confirmed by both immunofluorescence and electron microscopy. The levels of plasma IgA, IgA1 and Gd-IgA1 were all increased in donors with IgA deposition compared with those without IgA deposition (mean ± SD, 3.54 ± 0.505 versus 2.356 ± 0.265 mg/ml, p = 0.049; 3.003 ± 0.4048 versus 2.356 ± 0.265 mg/ml, p = 0.057; and 4.719 ± 0.4357 versus 3.356 ± 0.4707 ug/ml, p = 0.0440, respectively). Colocalized IgA1 and Gd-IgA1 indicated that there were galactose-deficient IgA1 deposits in the glomerular mesangium. While donors with IgA deposition showed lower levels of IgG anti-glycan antibodies than patients with IgA nephropathy (37.71 ± 8.886 versus 78.86 ± 5.155 units/ml, p = 0.001). CONCLUSIONS: The immune features of donors with IgA deposition, including IgA1 and Gd-IgA1 deposition, were similar to those of patients with IgA nephropathy, but donors with IgA deposition had lower levels of antiglycan antibodies, which may explain the subclinical status of IgA deposition in donors. Mesangial IgA deposition was common in the Chinese blood related donors cohort, further large study with both living and cadaveric donor kidneys was still needed to confirm these findings.

Metabolic syndrome is associated with improved cancer-specific survival in patients with localized clear cell renal cell carcinoma.

BACKGROUND: Metabolic syndrome (MetS) has been found to be prevalent in cancer and have implications in cancer outcomes. In this study, we attempted to evaluate the prognostic value of MetS in localized clear cell renal cell carcinoma (ccRCC) patients. METHODS: We retrospectively collected clinicopathological data and pre-treatment laboratory test results of 480 patients with localized (T1-2N0M0) ccRCC undergoing radical or partial nephrectomy in Peking University First Hospital. MetS was diagnosed by criteria of the 2004 Chinese Medical Association Diabetes Society. Univariate and multivariate analyses were conducted to analyze the association between clinicopathological characteristics, MetS, and disease outcomes. RESULTS: In our cohort, 136 patients (28.3%) were diagnosed with MetS. Among them, 113 (83.1%) were men, suggesting that men were more likely to have MetS. This syndrome was also associated with increased pre-treatment creatinine levels. Median follow-up time was 70 months (range, 1-118 months) and 5-year overall survival (OS) rate was 92%. MetS was an independent favorable factor of cancer-specific survival (CSS) (P=0.017), and similar results were observed in Fuhrman nuclear grade 1-2 ccRCC patients by further analysis. Neither of the four components of the MetS (hypertension, diabetes mellitus, overweight/obesity and dyslipidemia) was an independent predictor of CSS. Patients who met more than 3 of the 4 criteria for MetS had higher CSS than those who met fewer than 2 criteria. CONCLUSIONS: MetS is an independent prognostic factor for better CSS in localized ccRCC patients.

Expression of programmed cell death-ligand 1 in primary testicular diffuse large B cell lymphoma: A retrospective study.

The present study evaluated programmed cell death-ligand 1 (PD-L1) expression in tumor cells and in the tumor microenvironment (TME) and its association with clinical data in primary testicular diffuse large B cell lymphoma (DLBCL). PD-L1 was determined by immunohistochemistry in 30 patients with primary testicular DLBCL and assessed for associations with clinical characteristics, progression-free survival (PFS) and overall survival (OS). The mean patient age was 62.2 years. Overall, 10 (33.3%) patients had advanced-stage (stage III/IV) disease and 14 (46.7%) patients had an International Prognostic Index (IPI) of ≥3. The median follow-up time following orchiectomy was 23.5 months. During this time, 10 (33.3%) patients experienced disease progression and 11 (36.7%) patients succumbed. PD-L1 expression in tumor cells and in the TME was detected in 20 (66.7%) and 13 (43.3%) patients, respectively. PD-L1 expression on tumor cells and in the TME was higher in those at an early stage compared with patients with an advanced stage of disease (P=0.045 and 0.017, respectively). In addition, PD-L1 expression in tumor cells was higher in patients with a low IPI compared with those with a high IPI (P=0.019). A Kaplan-Meier analysis identified no association of PD-L1 expression on tumor cells with PFS (P=0.763) or OS (P=0.531), or of PD-L1 expression in the TME with PFS (P=0.572) or OS (P=0.934). The present study demonstrated that PD-L1 expression in tumor cells and in the TME was higher in patients at an early stage of disease compared with those at an advanced stage, and that PD-L1 expression on tumor cells was higher in patients with a low IPI than in those with a high IPI. Furthermore, PD-L1 expression in tumor cells and in the TME was not associated with PFS or OS.

Activation of cGMP/PKG/p65 signaling associated with PDE5-Is downregulates CCL5 secretion by CD8 + T cells in benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common urological disease in elderly men, but the underlying pathophysiological mechanisms are complex and not fully understood. Phosphodiesterase type 5 inhibitors (PDE5-Is) used to treat BPH could upregulate the cyclic guanosine monophosphate (cGMP)-dependent protein kinase G (PKG) signaling, which was shown to blunt inflammation in the prostate. Our previous findings indicate that CD8+ T cells promote the proliferation of BPH epithelial cells (BECs) in low androgen conditions through secretion of CCL5; however, the role of the cGMP/PKG pathway in the process is unclear. METHODS: Paraffin-embedded tissues were used for expression quantity of CD8+ T cells, CCL5, cyclin D1, and PDE5 protein by immunohistology in prostate specimens which were/were not treated with finasteride 5 mg daily for at least 6 months before surgery. BPH-1 cells were cocultured with or without CD8 + T cells or PDE5-Is in low androgen conditions for 4 days. The conditioned media, BPH-1 cells, and CD8 + T cells were harvested for the subsequent experiments. The quantitative polymerase chain reaction was used for assaying the level of messenger RNA expression of CCL5. CCL5 in the conditioned media was detected by the enzyme-linked immunosorbent assay. The effect of PDE5-Is on cocultured BPH-1/CD8 + T-cell proliferation was detected by the cell counting kit-8. A high-fat diet (HFD)-induced prostatic hyperplasia rat model was used to investigate the effect of cGMP/PKG activation in CD8 + T cells in vivo. RESULTS: CD8+ T-cell infiltration into human BPH tissues was positively correlated with the expression of CCL5, cyclin D1, and PDE5, whereas in an HFD-induced prostatic hyperplasia rat model, the activation of the cGMP/PKG signaling by a PDE5-I could suppress the CD8 + T-cell infiltration and the CCL5 and cyclin D1 expression. Furthermore, the activation of the cGMP/PKG pathway inhibited CCL5 secretion by CD8 + T cells by downregulating nuclear factor-κB p65 phosphorylation, which reduced the growth of BPH-1 through CCL5/STAT5/CCND1 signaling. CONCLUSIONS: Our results indicate that the upregulation of the cGMP/PKG/p65 signaling reduces CCL5 secretion in CD8 + T cells, which in turn decreases the proliferation of BECs in low androgen conditions, suggesting that the combination of 5α reductase inhibitors lowering androgen levels and PDE5-Is may be a novel, more effective treatment for BPH patients.

DDD score for renal tumor: An intuitive and comprehensive anatomical scoring system to access the outcomes of retroperitoneal laparoscopic partial nephrectomy.

OBJECTIVE: To present a DDD scoring system in assessing the complexity and outcomes of retroperitoneoscopic nephron-sparing surgery for kidney tumor. METHODS: We retrospectively evaluated 232 patients who underwent retroperitoneoscopic nephron-sparing surgery between January 2013 and September 2017 for a renal tumor. Both the DDD score and RENAL score were used to classify the tumors. The DDD score consisted of the maximal tumor diameter inside the kidney, the maximal tumor depth into the medulla or collecting system and the minimal distance from the tumor to the main renal vessels. RESULTS: The DDD scoring systems were significantly associated with warm ischemia time (P = 0.007) and estimated blood loss (P = 0.017). There was an insignificant positive correlation between the DDD score and the operative time (P = 0.051). Meanwhile, the RENAL score had a significant correlation with the decreasing value of the estimated glomerular filtration rate. Patients with high or moderate DDD scores had a 13.6-fold or 8.4-fold risk of overall complications than those with low DDD scores, respectively (all P < 0.05). As for RENAL score, patients with moderate scores had a 2.9-fold risk of overall complications compared with patients in the low scores group (P = 0.004). In the receiver operating characteristic curve analysis, the DDD score had the greatest area under the curve for overall complications (area under the curve 0.625, P = 0.009), which was more than the RENAL score (area under the curve 0.620, P = 0.013). CONCLUSIONS: The DDD score is an intuitive renal tumor scoring system that is more effective than the RENAL score in complexity assessment, and marginally better in prediction of the risk of overall complications of retroperitoneal laparoscopic nephron-sparing surgery.

M2 macrophage-mediated interleukin-4 signalling induces myofibroblast phenotype during the progression of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a progressive disease in elderly men, but potential factors accelerating its progression remain largely unknown. The aim of this study was to elucidate the factors affecting BPH progression by understanding the complex mechanisms causing early- progressed BPH, which progresses rapidly and requires surgical intervention before the age of 50. Three groups of human prostate tissue samples, from patients with early-progressed BPH, age-matched prostate and elderly BPH tissues, were collected (n = 25 each). We compared these tissues to determine the histologic features and molecular mechanisms underlying BPH progression. We found that early-progressed BPH samples were characterised by aberrant stromal hyper-proliferation, collagen deposition and increased M2 macrophage infiltration, compared to those from age-matched prostate and elderly BPH tissues. The M2 macrophage-fibroblast co-culture system demonstrated that the myofibroblast phenotypes were strongly induced only in fibroblasts from the early-progressed BPH samples, while the co-cultured M2 macrophages expressed high levels of pro-fibrotic cytokines, such as IL4 and TGFß1. M2 macrophage-derived IL4, but not TGFß1, selectively induced the myofibroblast phenotype through the JAK/STAT6, PI3K/AKT and MAPK/ERK signalling pathways in the early-progressed BPH prostate fibroblasts. Taken together, our results indicate that induction of the myofibroblast phenotype may lead to BPH progression through M2 macrophage-mediated IL4 signalling, and that IL4 may represent a potential therapeutic target, allowing the prevention of M2 macrophage activation and fibroblast-to-myofibroblast differentiation.

What is the impact of human leukocyte antigen mismatching on graft survival and mortality in renal transplantation? A meta-analysis of 23 cohort studies involving 486,608 recipients.

BACKGROUND: The magnitude effects of human leukocyte antigen (HLA) mismatching on post-transplant outcomes of kidney transplantation remain controversial. We aim to quantitatively assess the associations of HLA mismatching with graft survival and mortality in adult kidney transplantation. METHODS: We searched PubMed, EMBASE and the Cochrane Library from their inception to December, 2016. Priori clinical outcomes were overall graft failure, death-censored graft failure and all-cause mortality. RESULTS: A total of 23 cohort studies covering 486,608 recipients were selected. HLA per mismatch was significant associated with increased risks of overall graft failure (hazard ratio (HR), 1.06; 95% confidence interval (CI), 1.05-1.07), death-censored graft failure (HR: 1.09; 95% CI 1.06-1.12) and all-cause mortality (HR: 1.04; 95% CI: 1.02-1.07). Besides, HLA-DR mismatches were significant associated with worse overall graft survival (HR: 1.12, 95% CI: 1.05-1.21). For HLA-A locus, the association was insignificant (HR: 1.06; 95% CI: 0.98-1.14). We observed no significant association between HLA-B locus and overall graft failure (HR: 1.01; 95% CI: 0.90-1.15). In subgroup analyses, we found recipient sample size and ethnicity maybe the potential sources of heterogeneity. CONCLUSIONS: HLA mismatching was still a critical prognostic factor that affects graft and recipient survival. HLA-DR mismatching has a substantial impact on recipient's graft survival. HLA-A mismatching has minor but insignificant impact on graft survival outcomes.

Taxus chinensis ameliorates diabetic nephropathy through down-regulating TGF-ß1/Smad pathway.

Diabetic nephropathy (DN) is one of the common microvascular complications of diabetes mellitus. Renal fibrosis is closely related to the deterioration of renal function. The present study aimed to investigate protective effect of Taxus chinensis on high-fat diet/streptozotocin-induced DN in rats and explore the underlying mechanism of action. The rat DN model was established via feeding high fat diet for 4 weeks and subsequently injecting streptozotocin (30 mg·kg-1 body weight) intraperitoneally. The rats with blood glucose levels higher than 16.8 mmol·L-1 were selected for experiments. The DN rats were treated with Taxus chinensis orally (0.32, 0.64, and 1.28 g·kg-1) once a day for 8 weeks. Taxus chinensis significantly improved the renal damage, which was indicated by the decreases in 24-h urinary albumin excretion rate, blood serum creatinine, and blood urea nitrogen. Histopathological examination confirmed the protective effect of Taxus chinensis. The thickness of glomerular basement membrane was reduced, and proliferation of mesangial cells and podocytes cells and increase in mesangial matrix were attenuated. Further experiments showed that Taxus chinensis treatment down-regulated the expression of TGF-ß1 and α-SMA, inhibited phosphorylation of Smad2 and Smad3. These results demonstrated that Taxus chinensis alleviated renal injuries in DN rats, which may be associated with suppressing TGF-ß1/Smad signaling pathway.

The impact of human leukocyte antigen mismatching on graft survival and mortality in adult renal transplantation: A protocol for a systematic review and meta-analysis.

BACKGROUND: Human leukocyte antigen (HLA) was important biological barrier to a successful transplantation. Quantitative evaluations of the effect of HLA mismatching on heart, liver, umbilical cord blood, and hematopoietic stem cell transplantation, have previously been reported. In new era of immunosuppression, the reported magnitude effect of HLA mismatching on survival outcomes of kidney transplantation was controversial. In addition, the current kidney allocation guideline recommendations in different countries were inconsistent in term of HLA mismatching. We undertake this study to conduct a systematic review and meta-analysis to assess the magnitude effect of HLA mismatching in adult kidney transplantation, with a particular focus on graft survival and mortality. METHODS: The present systematic review and meta-analysis protocol was conducted following the Meta-analysis of Observational Studies in Epidemiology protocol (MOOSE-P) and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis protocol (PRISMA-P). PubMed, EMBASE, Cochrane library Database will be searched without language restriction. Studies fulfill the following criteria will be eligible: included study cohorts comprising adult recipients; reported the association between HLA mismatching (per mismatches or HLA-A, -B, -DR mismatches) and posttransplant survival outcomes; provided effect estimates of hazard ratios (HRs) with 95% confidence interval (CIs). The incidence of measured outcomes was defined according to the European Renal Best Practice Transplantation Guidelines and Kidney Disease: Improving Global Outcomes Guidelines. RESULTS: This study will quantitatively assess the association of HLA per mismatches, DR-antigen mismatches, A-antigen mismatches, and B-antigen mismatches with survival outcomes of overall graft failure, death-censored graft failure, all-cause mortality, and mortality with a functioning graft. CONCLUSION: This study will determine the issues on what extent HLA compatibility influenced recipient and graft survival and which HLA antigen plays a more important role in kidney transplantation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017071894.

Effect of human leukocyte antigen mismatching on the outcomes of pediatric kidney transplantation: a systematic review and meta-analysis.

BACKGROUND: Kidney transplantation is regarded as the optimal treatment for pediatric patients with end-stage renal disease. Here, we address a controversial topic in pediatric kidney transplantation by performing a quantitative evaluation of the effect of human leukocyte antigen (HLA) mismatching on the outcomes of pediatric kidney transplantation. METHODS: We systematically searched PubMed, EMBASE and the Cochrane Library from their inception to 31 December 2016 for cohort studies assessing the risk ratio (RR) of HLA mismatching on pediatric kidney transplantation. Outcome measures included graft failure, rejection and all-cause mortality. RRs and 95% confidence intervals (CIs) were used as estimates of effect size in random-effect models. RESULTS: Eighteen studies comprising a total of 26 018 pediatric recipients were included in the evaluation. Compared with 0-1 HLA-DR mismatch, 2 mismatches significantly increased the risk of graft failure at 1 year (RR: 1.41, 95% CI: 1.11-1.80), 3 years (RR: 1.28, 95% CI: 1.08-1.52), 5 years (RR: 1.21, 95% CI: 1.04-1.41) and 10 years (RR: 1.30, 95% CI: 1.02-1.67). For HLA-A + B, the 5-year graft failure risk was higher for 2-4 mismatches compared with 0-1 mismatch (RR: 3.17, 95% CI: 1.20-8.36), but not for 3-4 compared with 0-2 mismatches (RR: 1.49, 95% CI: 0.79-2.80). CONCLUSIONS: Based on pooled analysis, HLA-DR and HLA-A + B are important factors affecting post-transplant outcomes, especially graft failure, in pediatric recipients. Additional randomized controlled trials with higher quality evidence are needed for further investigation.

Prognostic significance of PD-L1 expression on tumor cells and tumor-infiltrating mononuclear cells in upper tract urothelial carcinoma.

Immunotherapy targeting the programmed death-1 (PD-1) receptor/PD-1 ligand (PD-L1) pathway has shown promising results in several malignancies. However, the prognostic significance of PD-L1 expression remains unknown in patients with upper tract urothelial carcinoma (UTUC). This study aimed to evaluate PD-L1 expression and its association with clinicopathological characteristics and oncological outcomes in UTUC patients. PD-L1 expression on tumor cells and tumor-infiltrating mononuclear cells (TIMCs), and E-cadherin and N-cadherin expression on tumor cells were assessed by immunohistochemistry in a cohort of 162 patients with UTUC. Associations of PD-L1 expression on tumor cells and TIMCs with clinicopathological characteristics and cancer-specific survival (CSS) were evaluated. Out of 162 patients, 20 (12.3%) and 35 (21.6%) had positive PD-L1 expression on tumor cells and TIMCs, respectively. Decreased E-cadherin expression was associated with PD-L1 positivity on tumor cells (P = 0.048) and PD-L1 negativity on TIMCs (P = 0.033). PD-L1 expression on tumor cells was higher in patients with preoperative chronic kidney disease (CKD) stage 4-5 than in those with no CKD or CKD stage 1-3 (P = 0.011). PD-L1 was differentially expressed in tumor cells and TIMCs in UTUC. Multivariate analyses revealed that PD-L1 expression on tumor cells independently predicted shorter CSS (P = 0.012), whereas PD-L1 expression on TIMCs independently predicted longer CSS (P = 0.034).

CD8+ T cells promote proliferation of benign prostatic hyperplasia epithelial cells under low androgen level via modulation of CCL5/STAT5/CCND1 signaling pathway.

Previous studies by our group have shown that low intra-prostatic dihydrotestosterone (DHT) induced BPH epithelial cells (BECs) to recruit CD8+ T cells. However, the influence of the recruited CD8+ T cells on BECs under a low androgen level is still unknown. Here, we found CD8+ T cells have the capacity to promote proliferation of BECs in low androgen condition. Mechanism dissection revealed that interaction between CD8+ T cells and BECs through secretion of CCL5 might promote the phosphorylation of STAT5 and a higher expression of CCND1 in BECs. Suppressed CCL5/STAT5 signals via CCL5 neutralizing antibody or STAT5 inhibitor Pimozide led to reverse CD8+ T cell-enhanced BECs proliferation. IHC analysis from Finasteride treated patients showed PCNA expression in BECs was highly correlated to the level of CD8+ T cell infiltration and the expression of CCL5. Consequently, our data indicated infiltrating CD8+ T cells could promote the proliferation of BECs in low androgen condition via modulation of CCL5/STAT5/CCND1 signaling. The increased secretion of CCL5 from the CD8+ T cells/BECs interaction might help BECs survive in a low DHT environment. Targeting these signals may provide a new potential therapeutic approach to better treat BPH patients who failed the therapy of 5α-reductase inhibitors.

Pretreatment serum pseudocholinesterase level as a novel prognostic biomarker for upper tract urothelial carcinoma.

PURPOSE: Pretreatment serum pseudocholinesterase (PChE) has been reported to be a prognostic predictor in several cancers. However, the prognostic significance of serum PChE level in patients with upper tract urothelial carcinoma (UTUC) remains unknown. METHODS: A total of 180 patients who underwent radical nephroureterectomy (RNU) for UTUC were included in this retrospective analysis. The associations of pretreatment serum PChE levels with clinicopathological characteristics and clinical outcomes were assessed. RESULTS: The median (IQR) pretreatment serum PChE level was 6385 (5449-7260) IU/L, and an optimal cutoff value of 5336 IU/L was set according to ROC analysis. Decreased pretreatment serum PChE levels were significantly correlated with older patient age, higher preoperative chronic kidney disease (CKD) stage and pT stage (all P < 0.05). On multivariate analysis, adjusting for preoperative variables, decreased pretreatment serum PChE levels independently predicted higher pT stage (P = 0.011). Moreover, Kaplan-Meier curves suggested that patients with PChE levels <5336 IU/L were predicted to have a shorter overall survival (OS) and cancer-specific survival (CSS) than those with PChE levels ≥5336 IU/L (both P < 0.001). On multivariate analysis, decreased pretreatment serum PChE levels were significantly associated with shorter OS (HR 0.553; 95 %CI 0.322-0.951; P = 0.032) and CSS (HR 0.484; 95 %CI 0.269-0.870; P = 0.015). CONCLUSIONS: Decreased pretreatment serum PChE level is an independent predictor for higher pT stage, shorter OS and CSS in patients with UTUC. Pretreatment serum PChE levels may act as a simple and effective parameter to predict prognosis for UTUC patients after RNU.

Preoperative Plasma Fibrinogen Level Represents an Independent Prognostic Factor in a Chinese Cohort of Patients with Upper Tract Urothelial Carcinoma.

BACKGROUND: Increased plasma fibrinogen is thought to contribute to tumor progression and metastasis. The association of plasma fibrinogen with clinicopathological characteristics, and the optimal cutoff with an ideal predictive value has not been fully determined in patients with upper tract urothelial carcinoma (UTUC). We aimed to investigate the clinical significance of this parameter in a Chinese cohort of patients with UTUC. METHODS: A retrospective study was conducted to analyze the clinical data of 184 operable UTUC patients in a Chinese cohort with a high incidence of chronic kidney disease (CKD). An optimal cutoff was set for further analysis according to validated web-based software. The associations of plasma fibrinogen with clinicopathological characteristics and survival were assessed. Multivariate analyses were performed to determine the independent prognostic factors. RESULTS: Elevated plasma fibrinogen was significantly associated with tumor necrosis, lymph node involvement, and a higher preoperative CKD stage, pathological tumor stage and grade (all P < 0.05). Kaplan-Meier analysis showed that plasma fibrinogen ≥ 3.54 g/L predicted a poorer overall and cancer-specific survival than < 3.54 g/L (P < 0.001 for both). Multivariate analyses revealed that elevated preoperative plasma fibrinogen was an independent negative prognostic factor for overall survival (HR = 2.026; 95% CI: 1.226-3.349; P = 0.006) and cancer-specific survival (HR = 1.886; 95% CI: 1.019-3.490; P = 0.043). CONCLUSIONS: Increased plasma fibrinogen was an independent prognostic risk factor for poor outcomes in UTUC. This parameter may serve as an effective biomarker with easy accessibility for evaluating prognosis for patients with UTUC.

Prognostic Significance of Preoperative Albumin-Globulin Ratio in Patients with Upper Tract Urothelial Carcinoma.

BACKGROUND: Preoperative albumin-globulin ratio (AGR) reflects both malnutrition and systemic inflammation in cancer patients. In particular, systemic inflammation has been reported to contribute to tumor progression and poor oncological outcome in various malignancies. However, the prognostic value of preoperative AGR in upper tract urothelial carcinoma (UTUC) has not been examined. METHODS: We retrospectively reviewed medical data of 187 operable UTUC patients in a Chinese cohort with a high incidence of chronic kidney disease (CKD). AGR was calculated as [AGR = albumin/(serum total protein-albumin)]. The associations of preoperative AGR with clinicopathologic characteristics and prognosis were assessed. Multivariate analyses using Cox regression models were performed to determine the independent prognostic factors. RESULTS: The median (IQR) preoperative AGR was 1.50 (1.30-1.70), and the optimal cutoff value was determined to be 1.45 according to the receiver operating curve analysis. Low AGR was significantly associated with female gender, high CKD stage and tumor grade (P < 0.05). Eighty-three patients died before the follow-up endpoint. Kaplan-Meier analysis showed that an AGR < 1.45 predicted significantly poorer overall and cancer-specific survivals compared to an AGR ≥ 1.45 (P < 0.001 and P = 0.008, respectively). Multivariate analyses showed that an AGR < 1.45 was an independent risk factor for poorer overall and cancer-specific survivals (P = 0.002 and P = 0.015, respectively). CONCLUSIONS: Preoperative AGR can act as an effective biomarker with easy accessibility for evaluating the prognosis of patients with UTUC. AGR should be applied in UTUC patients for risk stratification and determination of optimal therapeutic regimens.

Prognostic Impact of ALDH1 Expression in Transitional Cell Carcinoma of the Renal Pelvis.

AIM: To investigate the clinical significance of aldehyde dehydrogenase 1 (ALDH1) expression in the assessment of the pathological outcomes and prognosis of carcinoma of the renal pelvis through examination of ALDH1 expression in pathological specimens. MATERIALS AND METHODS: A total of 114 patients with carcinoma of the renal pelvis who underwent radical nephroureterectomy at the First Hospital of Peking University between September 2004 and August 2007 with continuity in data were included in this study. The expression of ALDH1 was examined in pathological specimens via immunohistochemistry, and was statistically analyzed in combination with corresponding clinical and pathological information. RESULTS: The pathological specimens from 37 patients (32.5%) exhibited positive ALDH1 expression, showing correlation with T stage (p=0.001) and G grade (p=0.010), as well as lymphatic and vascular infiltration (p=0.003), but these specimens did not correlate with tumor multi-focality (p=0.398). The univariate analysis showed that tumor grade (p=0.001) and ALDH1 positive expression (p<0.001), as well as lymphatic and vascular infiltration (p=0.017) correlated with prognosis, and this analysis also showed that tumour, node and metastasis (TNM) stage (p=0.085), as well as occurrence of multiple tumors (p=0.166) had no significant correlation with prognosis. Multivariate analysis indicated advanced G grade (p=0.006) and ALDH1 expression as independent predictive factors for poor prognosis. A significant correlation was observed between positive ALDH1 expression and tumor relapse following radical resection (p<0.001). CONCLUSION: The cancer stem-like cell marker ALDH1 can be used as a predictive factor for adverse pathological outcomes and prognosis in transitional cell carcinoma. of the renal pelvis. Cancer stem cell theory plays an important role in the clinical study of transitional cell carcinoma of the upper urinary tract.

[Predictor analysis of PSA response of docetaxel combined with prednisone in the treatment of metastatic castration resistant prostate cancer].

OBJECTIVE: To investigate the factors that may predict the effectiveness of metastatic castration resistant prostate cancer (mCRPC) patients who received docetaxel plus prednisone treatment. METHODS: We retrospectively collected the clinical data of mCRPC patients who has received docetaxel chemotherapy in Peking University First Hospital between February 2010 and March 2015, and the clinical factors were analyzed using univariate analysis. RESULTS: A total of 60 cases of patients were treated, of whom 33 with complete clinical data were analyzed. PSA responsive was defined as PSA declining ≥50% of baseline and without progression according to RESCIST criteria. The median PSA at chemotherapy was 153.4 µg/L (6.6-9 952.0 µg/L), and a total of 20 cases (60.6%) were PSA responsive. Univariate analysis found that lower Gleason score (Gleason scores≤7) (25% vs.72%, P=0.034), the existence of positive Lymph node (78% vs. 40%, P=0.032), the existence of visceral metastasis (80% vs. 44%, P=0.041) and baseline blood HGB value≤120 g/L (30% vs. 74%, P=0.024) were associated with chemotherapy effectiveness. CONCLUSION: High Gleason score, lymph node metastasis, visceral metastasis and normal HGB level may predict PSA response after docetaxel-based chemotherapy.