Publications by authors named "Liangren Liu"

74 Publications

Levofloxacin Versus Ciprofloxacin in the Treatment of Urinary Tract Infections: Evidence-Based Analysis.

Front Pharmacol 2021 8;12:658095. Epub 2021 Apr 8.

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.

Urinary tract infections (UTIs) are one of the most common bacterial infections acquired both in community and hospital. Fluoroquinolones, represented by levofloxacin and ciprofloxacin, are widely used for treatment of UTIs. However, it remains controversial for the comparison between the 2 drugs, which propelled us to conduct the first evidence-based research on this topic. To establish their relative efficacy and safety, we searched Pubmed, embase, and Web of Science for randomized controlled trials (RCTs) for UTIs. A total of 5 RCTs were finally included, involving 2,352 patients and a systematic review and meta-analysis were performed to compare the end-of-therapy and posttherapy clinical success rate, microbial eradication rate and adverse event rate. Jadad score and Review Manager 5.3.0 version were applied respectively to evaluate the study quality and heterogeneity. There was no significant difference between levofloxacin and ciprofloxacin group in end-of-therapy or posttherapy clinical success rate and microbial eradication rate ( > 0.05). As for adverse event rate, the 2 drugs were comparable and both safe for clinical use. Based on one included trial and pharmacological research, we raised hypothesis that levofloxacin was superior to ciprofloxacin for treatment of E. coli-induced chronic bacterial prostatitis (CBP) and it required a further study to prove it.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.658095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060646PMC
April 2021

Red and processed meat consumption and cancer outcomes: Umbrella review.

Food Chem 2021 Mar 27;356:129697. Epub 2021 Mar 27.

Department of Urology/Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address:

The purpose of this umbrella review was to evaluate the quality of evidence, validity and biases of the associations between red and processed meat consumption and multiple cancer outcomes according to existing systematic reviews and meta-analyses. The umbrella review identified 72 meta-analyses with 20 unique outcomes for red meat and 19 unique outcomes for processed meat. Red meat consumption was associated with increased risk of overall cancer mortality, non-Hodgkin lymphoma (NHL), bladder, breast, colorectal, endometrial, esophageal, gastric, lung and nasopharyngeal cancer. Processed meat consumption might increase the risk of overall cancer mortality, NHL, bladder, breast, colorectal, esophageal, gastric, nasopharyngeal, oral cavity and oropharynx and prostate cancer. Dose-response analyses revealed that 100 g/d increment of red meat and 50 g/d increment of processed meat consumption were associated with 11%-51% and 8%-72% higher risk of multiple cancer outcomes, respectively, and seemed to be not correlated with any benefit.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.foodchem.2021.129697DOI Listing
March 2021

Clinical Characteristics and Prognostic Factors of Testicular Sarcoma: A Population-Based Study.

Front Oncol 2021 25;11:614093. Epub 2021 Feb 25.

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.

Objectives: To study clinical characteristics and factors that may affect the prognosis of testicular sarcoma patients.

Patients And Methods: In the Surveillance Epidemiology and End Results database (2006-2016), people with testicular sarcoma were enrolled in our research. Multivariable Cox proportional hazard model and Multivariable Logistic regression model were used to compare the impact of different factors on cancer-specific survival, localized metastasis, and distant metastasis.

Results: This research was based on the registry information of 158 testicular sarcoma patients. All patients with a median age of 17.00 (1.00-93.00) years were pathologically diagnosed with orchiectomy or needle biopsy specimens. Patients with Grade I, II, III, and IV testicular sarcoma accounted for 34.29% (n = 24), 10.10% (n = 7), 22.86% (n = 16), and 32.86% (n = 23) of all patients, respectively. There were 42 (30.43%), 53 (38.41%), 15 (10.87%), 20 (14.49%), 5 (3.62%), 3 (2.17%) patients with Tis, T1, T2, T3, T4, and >T4 (the invasion degree exceeded the staging system of testicular cancer) disease respectively. Among all included patients, localized metastasis occurred in 31 (20.13%) patients, distant metastasis was found in 28 (18.18%) patients during observation, and 61.69% (n = 95) had no metastasis. Thirty-two (20.25%) patients died of this cancer. According to our study, patients with distant metastasis [OR = 17.86, 95% CI (4.63-68.84), p < 0.0001] and T3 disease [OR = 4.13, 95% CI (1.10-15.53), p = 0.0359] were more likely to die of this cancer. Patients with advanced T stage were more likely to occur distant metastasis, [OR = 13.91, 95% CI (1.80-107.54), p = 0.0116] for T3 and [OR = 16.36, 95% CI (1.36-196.21), p = 0.0275] for T4.

Conclusions: According to our research, factors including metastasis and higher T stage were significantly related with poorer prognosis of testicular sarcoma. Higher T stage was also found to be a risk factor of distant metastasis. The recognization of these poor prognostic factors may allow physicians to make comprehensive and appropriate management decision for testicular sarcoma patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.614093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959772PMC
February 2021

The relationships between bariatric surgery and sexual function: current evidence based medicine.

BMC Urol 2020 Oct 2;20(1):150. Epub 2020 Oct 2.

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Background: Controversy remains despite several studies have discussed the role of bariatric surgery in improving male's sexual function. This study aims to evaluate the efficacy of bariatric surgery in promoting male's erectile function.

Methods: PubMed, EMbase, The Cochrane Library, CNKI and Clinical Trails.gov were searched from database inception to May 2019. The language of publication was limited in English. The International Index of Erectile Function (IIEF) score and Brief Male Sexual Function Inventory (BSFI) score were set as the primary outcome.

Results: Eleven studies with a total of 370 patients were enrolled in this meta-analysis. The results showed significant improvement in the IIEF score (erectile function: MD = 5.33, 95% CI 4.12-6.54; intercourse satisfaction: MD = 2.57, 95% CI 1.19-3.94; orgasmic function: MD = 0.50, 95%CI 0.60-0.94; overall satisfaction: MD = 1.67, 95% CI 0.78-2.56; sexual desire: MD = 1.27, 95% CI 0.61-1.93; total erectile function: MD = 7.21, 95% CI 4.33-10.10) and the BSFI score (erection: MD =2.53, 95% CI 2.39-2.67; ejaculation: MD = 1.40, 95% CI 1.28-1.51; desire: MD =1.40, 95% CI 1.32-1.49; problem assessment: MD = 2.20, 95% CI 2.06-2.34; sexual satisfaction: MD = 0.70, 95% CI 0.60-0.76) in obese individuals after bariatric surgery.

Conclusions: This systematic review and meta-analysis indicated that bariatric surgery could be effective in promoting males's sexual function for obese individuals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12894-020-00707-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532646PMC
October 2020

Steroid Sulfatase Stimulates Intracrine Androgen Synthesis and is a Therapeutic Target for Advanced Prostate Cancer.

Clin Cancer Res 2020 Nov 14;26(22):6064-6074. Epub 2020 Sep 14.

Department of Urologic Surgery, University of California, Davis, Sacramento, California.

Purpose: Most patients with prostate cancer receiving enzalutamide or abiraterone develop resistance. Clinical evidence indicates that serum levels of dehydroepiandrosterone sulfate (DHEAS) and biologically active DHEA remain in the high range despite antiandrogen treatment. The conversion of DHEAS into DHEA by steroid sulfatase (STS) may contribute to sustained intracrine androgen synthesis. Here, we determine the contribution of STS to treatment resistance and explore the potential of targeting STS to overcome resistance in prostate cancer.

Experimental Design: STS expression was examined in patients and cell lines. , STS activity and expression were modulated using STS-specific siRNA or novel STS inhibitors (STSi). Cell growth, colony formation, androgen production, and gene expression were examined. RNA-sequencing analysis was conducted on VCaP cells treated with STSi. Mice were treated with STSis with or without enzalutamide to determine their effects .

Results: STS is overexpressed in patients with castration-resistant prostate cancer (CRPC) and resistant cells. STS overexpression increases intracrine androgen synthesis, cell proliferation, and confers resistance to enzalutamide and abiraterone. Inhibition of STS using siRNA suppresses prostate cancer cell growth. Targeting STS activity using STSi inhibits STS activity, suppresses androgen receptor transcriptional activity, and reduces the growth of resistant C4-2B and VCaP prostate cancer cells. STSis significantly suppress resistant VCaP tumor growth, decrease serum PSA levels, and enhance enzalutamide treatment and .

Conclusions: These studies suggest that STS drives intracrine androgen synthesis and prostate cancer proliferation. Targeting STS represents a therapeutic strategy to treat CRPC and improve second-generation antiandrogen therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-20-1682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669645PMC
November 2020

Biomaterial 3D collagen I gel culture model: A novel approach to investigate tumorigenesis and dormancy of bladder cancer cells induced by tumor microenvironment.

Biomaterials 2020 10 2;256:120217. Epub 2020 Jul 2.

Department of Urology, Institute of Urology and National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China. Electronic address:

The high potential for cancer relapse has emerged as a crucial challenge of human bladder cancer treatment. To date, those stem-like bladder cancer cells (BCSCs) have been considered as seeds that induce frequent tumor recurrence. However, the cell origin of cancer stem cells (CSCs) is still a controversial issue, due in part to the findings that CSCs not only origin from normal stem cells but also converted from differentiated tumor cells. Here, we describe a biomaterial 3D collagen I gel culture system, where non-tumorigenic cells can obtain tumorigenic potential and revert back into CSCs through the integrin α2β1/PI3K/AKT/NF-κB cascade, resulting in the tumorigenesis in bladder tissues. Furthermore, inhibiting this integrin α2β1/PI3K/AKT/NF-κB signal pathways can significantly impair the tumorigenic capacity of CSCs. Simultaneously, in vivo studies demonstrate that IFN-γ secreted by T cells can trigger those CSCs into dormancy through the IDO/Kyn/AHR/P27 cascade, which elicit chemotherapy resistance and cancer relapse. To address the challenges of suppressing bladder tumor growth and preventing tumor reoccurrence, we use IDO and integrin α2β1 signal pathway inhibitors combine with chemotherapeutic agents to awaken dormant bladder CSCs and inhibit their tumorigenic ability as well as effectively eliminate CSCs. The therapeutic approaches we propose provide new insights for eradicating tumors and reducing bladder cancer relapse after therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biomaterials.2020.120217DOI Listing
October 2020

The Efficiency and Safety of Transperitoneal versus Extraperitoneal Robotic-Assisted Radical Prostatectomy for Patients with Prostate Cancer: A Single Center Experience with 1-year Follow-up.

Urol J 2020 07 21;17(5):480-485. Epub 2020 Jul 21.

Department of Urology/Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, P.R. China.

Purpose: Several studies have compared the short-term outcomes of extraperitoneal robot-assisted laparoscopic radical prostatectomy (EP-RALP) and transperitoneal RALP (TP-RALP). The study was designed to evaluate the long-term outcomes of the two methods.

Materials And Methods: A prospective, non-randomized study was conceived. The demographics and operative outcomes of patients with prostate cancer undergoing RALP from September 2016 to January 2017 at our center were included.

Results: A total of eighty-six patients were enrolled. Thirty-seven patients underwent EP-RALP, and forty-nine patients received TP-RALP. No significant difference was observed in age, body mass index, pathological T stage, pathological N stage, M stage, 2014 International Society of Urological Pathology group, comorbidities or American Society of Anesthesiologists score. A lower preoperative prostate-specific antigen (PSA) was detected in the EP-RALP group. No significant differences were observed in overall operation time, robotic console time, surgical margin status, postoperative hospitalization time, drop of hemoglobin and complications, except that patients with EP-RALP had a shorter time to first exsufflation after surgery than those with TP-RALP (41.35 vs. 51.80 h, P < .001). Postoperative PSA until 12 months was deemed comparable in both groups. Complete continence until 12 months after surgery was desirable but not significantly different between two groups (75.0% in EP- RALP vs. 86.7%. in TP-RALP, P = .179).

Conclusion: The long-term outcomes of EP-RALP were analogous to those of TP-RALP. Therefore, EP-RALP is an alternative approach for patients with localized prostate cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.22037/uj.v16i7.5475DOI Listing
July 2020

Evaluating the Effect of Cryptorchidism on Clinical Stage of Testicular Seminoma.

Cancer Manag Res 2020 23;12:4883-4888. Epub 2020 Jun 23.

Department of Urology/Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China.

Objective: To study the effect of cryptorchidism on clinical stage (CS) of testicular seminoma (TS).

Patients And Methods: In the Surveillance Epidemiology and End Results (SEER) database (2006-2016), people with TS were enrolled in our research. Multivariable logistic regression models were constructed to compare the impact of cryptorchidism on CS.

Results: This research was based on the registry information of 12,991 TS patients. All patients with a median age of 36 (13-107) years were pathologically diagnosed with orchiectomy or needle biopsy specimens. Patients with CS I, II, and III TS accounted for 70.68% (n = 9182), 8.30% (n = 1078), and 5.75% (n = 747) of all patients, respectively; still there were 15.27% (n = 1984) of patients whose CS could not be identified or was not available. Among all included patients, 43.45% (n = 5644) of them had normal testis, 2.93% (n = 272) had cryptorchidism, and the primary site of 54.46% (n = 7075) of patients' testis was unavailable. According to our study, patients with cryptorchidism were more likely to suffer advanced CS [OR=1.14, 95% CI (1.01-1.28), p=0.0407]. Furthermore, this effect became more remarkable after adjusting for other factors including age, region, marital status, race, year of diagnosis and laterality [OR=1.23, 95% CI (1.13-1.32), p<0.0001].

Conclusion: According to this study, TS patients with cryptorchidism would be at a higher risk of suffering advanced cancer than patients with normal testis. It demonstrates that surgical correction for cryptorchidism should be timely, and specific management should be conducted on this kind of TS patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CMAR.S236618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320749PMC
June 2020

Inflammatory Myofibroblastic Tumor of the Urinary System on Computed Tomography at a High-Volume Institution in China.

Urol Int 2020 11;104(11-12):960-967. Epub 2020 Jun 11.

Department of Urology, West China Hospital, Sichuan University, Chengdu, China.

Objective: Inflammatory myofibroblastic tumors (IMTs) of the urinary system are relatively rare and often misdiagnosed. We aimed to summarize and analyze the clinical manifestations, imaging features, management, and follow-up of renal and bladder IMTs.

Methods: In this retrospective study, 22 patients with IMT pathologically verified between 2009 and 2018 were included. Epidemiologic, clinical, pathologic, and imaging findings were recorded. Tumor size, location, and shape were analyzed and summarized.

Results: There were 22 patients with a median age of 45 years (range: 20-74), including 14 patients with renal IMT and 8 patients with bladder IMT, who met the eligibility criteria. In 21 patients, IMT appeared as a single lesion, whereas 1 patient showed bilateral renal lesions. Surgical resection was the sole therapy, and follow-up information was acquired from 13 individuals with no evidence of recurrence or metastasis. In our study, a slightly hypodense or isodense homogeneous tumor with a clear boundary was more often seen. On contrast-enhanced computed tomography (CT), they were often manifesting as a slightly heterogeneous enhancement.

Conclusions: The nature of IMTs might cause a lack of generalizability. However, it will be useful to know that there are various CT demonstrations of IMTs. CT images are useful for the detection, location, and characterization of urinary IMTs, which can help in better clinical decision-making and can also be an optimal imaging technique for follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000506779DOI Listing
June 2020

Detection of Prostatic Inflammation From Peripheral Lymphocyte Count and Free/Total PSA Ratio in Men With LUTS/BPH.

Front Pharmacol 2020 30;11:589. Epub 2020 Apr 30.

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.

Objective: Identifying biomarkers of prostatic inflammation has been a question of great interest in the development of anti-inflammatory pharmacotherapy for lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). Systemic inflammation and serum prostate-specific antigen (PSA) have been linked with prostatic inflammation. This study set out to develop a diagnostic model for prostatic inflammation using clinical and laboratory parameters.

Methods: We included LUTS/BPH patients undergoing transurethral resection of the prostate. The severity of prostatic inflammation was determined by pathological review. Clinical manifestations and preoperative laboratory test results were recorded. We used LASSO regression with 10-fold cross-validation to select variables with the most diagnostic value of prostatic inflammation. Furthermore, we used multivariable logistic regression analysis to develop the diagnostic model, presented in a nomogram. The discrimination, calibration of the post-LASSO diagnostic model, and the model supplemented with clinical parameters were assessed. Decision curve analysis was performed.

Results: A total of 164 patients were included. Of all patients, 97 (59.1%) had no or mild prostatic inflammation, and 67 (40.9%) had moderate to severe prostatic inflammation. A higher peripheral white blood cell count, higher peripheral lymphocyte count, lower free/total (f/t) PSA ratio, and acute urinary retention history were associated with a higher risk of moderate to severe prostatic inflammation. Peripheral lymphocyte count and f/t PSA ratio were selected by the LASSO method and entered into the nomogram. The post-LASSO diagnostic model had an AUC of 0.756 (95% CI: 0.684-0.829) and good calibration. The addition of clinical parameters failed to show incremental diagnostic value. The decision curve analysis demonstrated that the post-LASSO laboratory nomogram was clinically useful.

Conclusion: Our findings demonstrated that peripheral lymphocyte count and f/t PSA ratio appear to be reliable diagnostic markers, based on which we build a clinically useful nomogram for prostatic inflammation. This diagnostic model could facilitate the development of anti-inflammatory pharmacotherapy for LUTS/BPH. Before this model is adopted in clinical practice, future validation is needed to determine its clinical utility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2020.00589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204507PMC
April 2020

Estrogen regulates the proliferation and inflammatory expression of primary stromal cell in benign prostatic hyperplasia.

Transl Androl Urol 2020 Apr;9(2):322-331

Department of Urology, West China Hospital, Sichuan University, Chengdu 610041, China.

Background: To investigate the expression of estrogen receptor (ER) in prostate tissues of benign prostatic hyperplasia (BPH) individuals, and the effects of estrogen regulating the proliferation and inflammatory expressions of primary prostate stromal cells in BPH.

Methods: A total of 44 human BPH prostate tissues were collected to explore the expression of ER by immunohistochemistry (IHC). Cell proliferation, mRNA and protein expressions were analyzed in primary prostate stromal cells treated with estrogen or estrogen plus fulvestrant through cell count kit-8 (CCK-8) assay, quantitative real-time polymerase chain reaction (qPCR), IHC and western blot, respectively.

Results: Firstly, ERβ was positive, and ERα was negative in the transition zone of prostate among all the 44 individuals with BPH. Secondly, the effects could be partially inhibited by fulvestrant, of estrogen promoting the proliferation of primary prostate stromal cells cultured in dulbecco's modified eagle medium (DMEM) supplemented with 2% fetal bovine serum (FBS). Thirdly, estrogen up-regulates the mRNA levels of C-C chemokine receptor type 3 (CCR3), CD40 ligand (CD 40L), C-X-C motif chemokine ligand 9 (CXCL9) and interleukin 10 (IL10), and down-regulates the mRNA levels of C-C chemokine receptor type 4 (CCR4) and interleukin 17C (IL17C). Then, the protein expressions of CCR3, CCR4, CD40L, IL10 and IL17C are positive, and CXCL9 is negative in the third-generation primary prostate stromal cells. Finally, the effects could be partially inhibited by fulvestrant, of estrogen up-regulating the protein levels of CD40L and IL10.

Conclusions: The expressions of ER in human BPH prostate tissues are zone-dependent. Estrogen promoting the proliferation of primary prostate stromal cells cultured in DMEM supplemented with 2% FBS. The expressions of CCR3, CCR4, CD 40L, IL17C, CXCL9 and IL10 are regulated by estrogen in primary prostate stromal cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/tau.2020.02.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214965PMC
April 2020

TMPO-AS1/miR-98-5p/EBF1 feedback loop contributes to the progression of bladder cancer.

Int J Biochem Cell Biol 2020 05 19;122:105702. Epub 2020 Feb 19.

Department of Urology, Institute of Urology, West China Hospital of Sichuan University, No.37 Guoxue Alley, Chengdu, 610000, Sichuan, PR China. Electronic address:

As reported in numerous studies, long non-coding RNAs (lncRNAs) exert significant effect on the regulation of tumor development. LncRNA TMPO antisense RNA 1 (TMPO-AS1) has been confirmed to be implicated in the development of several cancers. However, its clinical significance is still largely unknown in bladder cancer (BCa). In this study, high expression of TMPO-AS1 was revealed in BCa tissues and cell lines, and TMPO-AS1 predicted poor prognosis. Moreover, TMPO-AS1 facilitated cell growth. Additionally, TMPO-AS1 also boosted the migration and invasion of BCa cells. Mechanistically, overexpressed EBF transcription factor 1 (EBF1) in BCa cell was verified to promote the transcription of TMPO-AS1. Later, we found that TMPO-AS1 was a cytoplasmic RNA and could sponge miR-98-5p. Besides, it was validated that EBF1 is a target gene of miR-98-5p and negatively correlated with miR-98-5p in terms of expression level. According to the results of rescue experiments, we observed that EBF1 overexpression restored the repressive effect of TMPO-AS1 silencing on BCa development. Our research is the first to disclose the biological role and molecular mechanism of TMPO-AS1 in BCa, and TMPO-AS1 might be identified as a new therapeutic target for BCa patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biocel.2020.105702DOI Listing
May 2020

Comparative assessment of efficacy and safety of different treatment for overactive bladder children: A systematic review and network meta-analysis.

Asian J Urol 2019 Oct 13;6(4):330-338. Epub 2019 Apr 13.

Department of Urology, Institute of Urology, West China Hospital of Sichuan University, Chengdu, China.

Objective: To compare these managements focusing on the efficacy and safety to treat overactive bladder (OAB) in children through network meta-analysis (NMA).

Methods: We searched PubMed, Embase, the Cochrane Library Central Register of Controlled Trials (CENTRAL) and the reference lists up to May 1st, 2017. Data from eligible randomized controlled trails (RCT) studies including three different treatment options were extracted. The primary outcome was maximal voiding volume (MVV). We performed pairwise meta-analyses by random effects model and NMA by Bayesian model. We used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework to assess the quality of evidence contributing to each network estimate.

Results: Six RCTs (462 patients) comparing three different interventions fulfilled the inclusion criteria. A low risk of bias was shown for the majority of the study items. The results of NMA showed that compared with antimuscarinic drugs, Parasacral transcutaneous electrical nerve stimulation was associated with significant improvement in the MVV (mean difference [MD] = 58.50, 95% confidential interval [CI]: 45.95-69.52), followed by urotherapy group (MD = 21.03, 95% CI: 11.85-29.97). When it comes to the constipation, antimuscarinic drugs exerted significant benefit than PTENS (odds ratio [OR]: 0.22, 95% CI: 0.01-0.46). No significant difference was found between other treatments.

Conclusion: Compared with antimuscarinic drugs, PTENS was associated with significant better efficacy considering MVV, but more constipation events in OAB children. Antimuscarinic drugs showed remarkably better efficacy considering MVV and comparable safety profile compared with urotherapy. Clinicians should take all known safety and compliance of patients into account when choosing an optimal strategy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajur.2019.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872791PMC
October 2019

Clinical characteristics of testicular seminoma in individuals in West China: a 10-year follow-up study.

Cancer Manag Res 2019 14;11:7639-7645. Epub 2019 Aug 14.

Department of Urology/Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China.

Objective: To assess the clinical characteristics of testicular seminoma (TS).

Patients And Methods: A testicular cancer (TC) survey was conducted by the Department of Urology, West China Hospital, between 2008 and 2018. Tumors were classified according to the NCCN criteria such as age, tumor size, tumor marker levels, histopathology, clinical stage, initial treatment, follow-up, and clinical outcomes, were obtained from the database of our center.

Results: Among 155 registered cases of TC with seminomatous element, 127 cases of pure TS were analyzed. All 127 patients with a median age of 37 years were pathologically diagnosed with orchiectomy specimens. Orchiectomy, chemotherapy, and radiotherapy were the main treatments for these patients. Patients with clinical stages I, II, and III testicular cancer of accounted for 81.1% (n=103), 15.7% (n=20), and 3.2% (n=4) of all patients, respectively. After a median follow-up time of 50 months, five patients presented with relapse during follow-up, and one among them died. Of the patients with stage I TS (T1N0M0S0 CS IA), three patients who only underwent orchiectomy relapsed. Among patients with stage II TS (T1N1M0S1 CS IIA), one patient relapsed after orchiectomy, post-surgery chemotherapy and radiotherapy. In four patients with stage III disease (T2N1M1aS1 CS IIIA), one relapsed after orchiectomy and chemotherapy, and died shortly after salvage chemotherapy and radiotherapy due to recurrence. The median overall survival time was 50 months. In all patients, the 2-year overall survival and progression-free survival probabilitis were 98.6% and 98.8%, respectively.

Conclusion: The present study shows that patients with TS have good prognosis even at an advanced stage. Surveillance after orchiectomy was important for patients with CSI seminoma, and we recommend cisplatin-based chemotherapy as salvage therapy for patients with CSI seminoma. In addition, patients with a maximal tumor diameter >4 cm should undergo post-surgery chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CMAR.S215537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698585PMC
August 2019

Neoadjuvant chemotherapy before radical prostatectomy for locally advanced prostate cancer: Protocol for a systematic review and meta-analysis.

Medicine (Baltimore) 2019 Aug;98(35):e17060

Department of Urology and National Clinical Research Center for Geriatrics.

Background: To evaluate the effectiveness and safety of neoadjuvant chemotherapy (NAC) for locally advance prostate patients undergoing radical prostatectomy.

Methods: PubMed/Medline, EMBASE, Web of Science, Ovid, Web of Knowledge, and Cochrane Library will be searched for studies related to the topic. The identification, inclusion and exclusion flow charts will be conducted according to PRISMA guidelines. The identified reports will be critically appraised using GRADE approach. Bias and heterogeneity of included studies will be assessed, and outcome measurements from individual studies will be combined with 95% confidence interval using a fixed- or random-effects model if qualified.

Results: This study will provide evidence and data on the tolerance and efficacy of NAC followed by radical prostatectomy (RP).

Conclusion: The application of taxanes-based chemotherapy has been widened to metastatic hormone sensitive prostate cancer in recent years. To be more vigorous, whether neoadjuvant administration of these cytotoxic agents can improve the outcome of RP in locally advance prostate cancer patients has been explored. This study aims to synthesis data regarding the adverse effect, response rate, recurrence, and survival from multiple trials, and to guide the healthcare practitioners using an evidence-based approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000017060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736486PMC
August 2019

Association between CYP1A1 rs4646903 T > C genetic variations and male infertility risk: A meta-analysis.

Medicine (Baltimore) 2019 Aug;98(31):e16543

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu.

Background: Number of studies have been performed to investigate the relationship between the CYP1A1 rs4646903 polymorphism and male infertility risk, but the sample size was small and the results were conflicting. A meta-analysis was performed to assess these associations.

Methods: A systematic search was conducted to identify all relevant studies from Medline, Web of science, Embase, China biology medical literature database (CBM), China National Knowledge Infrastructure (CNKI), WanFang and Weipu (VIP) databases up to June 30, 2018. The odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of associations. All of the statistical analyses were conducted using Revman 5.3 and Stata 14.0.

Results: Ten studies involved 3028 cases and 3258 controls. Overall, significant association was observed between the CYP1A1 rs4646903 polymorphism and male infertility (C vs T: OR = 1.42, 95%CI = 1.14-1.76; CC vs TT: OR = 2.13, 95%CI = 1.36-3.34; CC vs CT+TT: OR = 1.96, 95%CI = 1.30-2.95; CC+CT vs TT: OR = 1.51, 95%CI = 1.16-1.97). In subgroup analysis by ethnic group, a statistically significant association was observed in Asians (C vs T: OR = 1.59, 95%CI = 1.22-2.08), but not in Non-Asians (C vs T: OR = 1.01, 95%CI = 0.79-1.30). Additionally, none of the individual studies significantly affected the association between CYP1A1 rs4646903 polymorphism and male infertility, according to sensitivity analysis.

Conclusion: Our meta-analysis supports that the CYP1A1 rs4646903 polymorphism might contribute to individual susceptibility to male infertility in Asians.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000016543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6709244PMC
August 2019

AKR1C3 Promotes AR-V7 Protein Stabilization and Confers Resistance to AR-Targeted Therapies in Advanced Prostate Cancer.

Mol Cancer Ther 2019 10 15;18(10):1875-1886. Epub 2019 Jul 15.

Department of Urologic Surgery, University of California, Davis, Davis, California.

The mechanisms resulting in resistance to next-generation antiandrogens in castration-resistant prostate cancer are incompletely understood. Numerous studies have determined that constitutively active androgen receptor (AR) signaling or full-length AR bypass mechanisms may contribute to the resistance. Previous studies established that AKR1C3 and AR-V7 play important roles in enzalutamide and abiraterone resistance. In the present study, we found that AKR1C3 increases AR-V7 expression in resistant prostate cancer cells through enhancing protein stability via activation of the ubiquitin-mediated proteasome pathway. AKR1C3 reprograms AR signaling in enzalutamide-resistant prostate cancer cells. In addition, bioinformatical analysis of indomethacin-treated resistant cells revealed that indomethacin significantly activates the unfolded protein response, p53, and apoptosis pathways, and suppresses cell-cycle, Myc, and AR/ARV7 pathways. Targeting AKR1C3 with indomethacin significantly decreases AR/AR-V7 protein expression and through activation of the ubiquitin-mediated proteasome pathway. Our results suggest that the AKR1C3/AR-V7 complex collaboratively confers resistance to AR-targeted therapies in advanced prostate cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1535-7163.MCT-18-1322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995728PMC
October 2019

Magnetic resonance imaging-guided targeted biopsy in risk classification among patients on active surveillance: A diagnostic meta-analysis.

Medicine (Baltimore) 2019 Jun;98(26):e16122

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu.

Background: The aim of this study was to assess the sensitivity and accuracy of magnetic resonance imaging-guided targeted biopsy (MRI-TB) in patients undergoing active surveillance (AS) procedure.

Methods: We searched databases to identify relevant studies which compared MRI-TB with systemic biopsy for diagnosing prostate cancer in patients on AS. Outcomes included sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under the curve (AUC) and publication bias of AS group, confirmatory biopsy group and follow-up biopsy group.

Results: Fourteen articles involving 1693 patients were included. In AS group, the sensitivity was 0.62 (95% confidence interval [CI], 0.57-0.68), specificity was 0.89 (95% CI, 0.87-0.90), NLR was 0.43 (0.31-0.60), PLR was 4.90 (3.50-6.86), DOR was 12.75 (7.22-22.51), and AUC was 0.8645. In confirmatory biopsy group, the sensitivity was 0.67 (0.59-0.74), specificity was 0.89 (0.86-0.91), NLR was 0.42 (0.27-0.65), PLR was 4.94 (3.88-6.30), DOR was 14.54 (9.60-22.02), and AUC was 0.8812. In follow-up biopsy group, the sensitivity was 0.35 (0.22-0.51), specificity was 0.88 (0.82-0.92), NLR was 0.76 (0.52-1.11), PLR was 3.06 (1.71-5.50), DOR was 4.41 (2.15-9.03), and AUC was 0.8367.

Conclusion: MRI-TB has a moderate-to-high diagnostic accuracy for diagnosing and reclassifying patients on AS with high specificity and AUC value under the SROC curve.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000016122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617438PMC
June 2019

Tumor-associated macrophages promote bladder tumor growth through PI3K/AKT signal induced by collagen.

Cancer Sci 2019 Jul 19;110(7):2110-2118. Epub 2019 Jun 19.

Department of Urology, Institute of Urology and National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China.

The tumor microenvironment is associated with various tumor progressions, including cancer metastasis, immunosuppression, and tumor sustained growth. Tumor-associated macrophages (TAMs) are considered an indispensable component of the tumor microenvironment, participating in the progression of tumor microenvironment remodeling and creating various compounds to regulate tumor activities. This study aims to observe enriched TAMs in tumor tissues during bladder cancer development, which markedly facilitated the proliferation of bladder cancer cells and promoted tumor growth in vivo. We determined that TAMs regulate tumor sustained growth by secreting type I collagen, which can activate the prosurvival integrin α2β1/PI3K/AKT signaling pathway. Furthermore, traditional chemotherapeutic drugs combined with integrin α2β1 inhibitor showed intensive anticancer effects, revealing an innovative approach in clinical bladder cancer treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cas.14078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609800PMC
July 2019

Surveillance of non-muscle invasive bladder cancer using fluorescence in situ hybridization: Protocol for a systematic review and meta-analysis.

Medicine (Baltimore) 2019 Feb;98(7):e14573

Department of Urology, Institute of Urology.

Background: To evaluate the diagnostic effectiveness and predictive value of fluorescence in situ hybridization (FISH) in the surveillance of non-muscle invasive bladder cancer (NMIBC).

Methods: PubMed/Medline, EMBASE, Web of Science, Ovid, Web of Knowledge, and Cochrane Library will be searched for studies related to the topic. The identification, inclusion, and exclusion flowcharts will be conducted according to preferred reporting items for systematic reviews and meta-analysis guidelines. The identified reports will be critically appraised according to the Newcastle-Ottawa scale, quality assessment of diagnostic accuracy studies-2 and standards for reporting of diagnostic accuracy 2015. Forest plots will be generated to display hazard ratios, sensitivities, and specificities. Pooled estimates with their 95% confidence intervals will be calculated using the bivariate model, the hierarchical summary receiver operating characteristic model and a fixed- or random-effects model.

Results: This study will provide evidence and data to form a comprehensive understanding of the value of FISH in the surveillance of NMIBC.

Conclusion: The diagnostic efficacy of FISH will be affected by post-therapy factors. However, FISH still could facilitate the surveillance of NMIBC owing to its non-invasive feature. This study will improve the clinical decision-making and enlighten the future research of NMIBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000014573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408111PMC
February 2019

A comprehensive comparison of fluorescence in situ hybridization and cytology for the detection of upper urinary tract urothelial carcinoma: A systematic review and meta-analysis.

Medicine (Baltimore) 2018 Dec;97(52):e13859

Department of Urology, Institute of Urology, West China Hospital, Sichuan University.

Objective: To compare the relative effectiveness of fluorescence in situ hybridization (FISH) and cytology in diagnosing upper urinary tract urothelial carcinoma (UUT-UC) and to evaluate the advantages and potential deficiencies of FISH analysis.

Methods: We performed a complete systematic review based on studies from PubMed/Medline, Embase, Web of Science, Ovid, Web of Knowledge, and Cochrane Library. We identified 2031 patients with strict criteria in 14 individual studies between January 2005 to November 2017 in accordance to preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines, we summarized the test performance using bivariate random effects models.

Results: FISH was superior to cytology in terms of pooled sensitivities (84.0%, 95% confidence interval [CI] 74.4-90.5% vs 40.0%, 95% CI 33.6-46.7%). FISH and cytology were similar to each other in terms of pooled specificities, which were 89.5% (95% CI 85.3-92.6%) for FISH and 95.9% (95% CI 91.2-98.1%) for cytology.

Conclusion: We confirm the superiority of FISH over cytology in terms of sensitivity and find similar diagnostic outcomes between them based on systematic analysis. Therefore, we demonstrate that FISH is extremely sensitive while still very reliable with a relatively low error rate for diagnosing UUT-UC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000013859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314722PMC
December 2018

Proteostasis by STUB1/HSP70 complex controls sensitivity to androgen receptor targeted therapy in advanced prostate cancer.

Nat Commun 2018 11 16;9(1):4700. Epub 2018 Nov 16.

Department of Urology, University of California Davis, Davis, 95817, CA, USA.

Protein homeostasis (proteostasis) is a potential mechanism that contributes to cancer cell survival and drug resistance. Constitutively active androgen receptor (AR) variants confer anti-androgen resistance in advanced prostate cancer. However, the role of proteostasis involved in next generation anti-androgen resistance and the mechanisms of AR variant regulation are poorly defined. Here we show that the ubiquitin-proteasome-system (UPS) is suppressed in enzalutamide/abiraterone resistant prostate cancer. AR/AR-V7 proteostasis requires the interaction of E3 ubiquitin ligase STUB1 and HSP70 complex. STUB1 disassociates AR/AR-V7 from HSP70, leading to AR/AR-V7 ubiquitination and degradation. Inhibition of HSP70 significantly inhibits prostate tumor growth and improves enzalutamide/abiraterone treatments through AR/AR-V7 suppression. Clinically, HSP70 expression is upregulated and correlated with AR/AR-V7 levels in high Gleason score prostate tumors. Our results reveal a novel mechanism of anti-androgen resistance via UPS alteration which could be targeted through inhibition of HSP70 to reduce AR-V7 expression and overcome resistance to AR-targeted therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-018-07178-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240084PMC
November 2018

Author Correction: Microsatellite analysis for differentiating the origin of renal angiomyolipoma and involved regional lymph node.

Sci Rep 2018 Oct 17;8(1):15601. Epub 2018 Oct 17.

Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-33870-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193011PMC
October 2018

Prognostic impact of preoperative anemia on upper tract urothelial carcinoma.

Medicine (Baltimore) 2018 Sep;97(37):e12300

Department of Urology, Institute of Urology Department of Emergency Department of Liver Surgery, Liver Transplantation Division Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

The aim of this study was to investigate the effect of preoperative anemia on the prognosis of patients who underwent radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC).A total of 620 patients with UTUC were retrospectively analyzed. Anemia was decided by preoperatively measured hemoglobin values based on the World Health Organization (WHO) classification. Kaplan-Meier method and Cox proportional hazards regression models were used to analyze the relationship between anemia and survival outcomes. The meta-analysis part was performed according to PRISMA guidelines.The median follow-up was 51 (range: 1-168) months. A total of 246 patients had preoperative anemia in our cohort. Anemia was found to be related to high-grade (P < .001), sessile architecture (P = .001), advanced T stage (P < .001), lymphovascular invasion (LVI) (P = .006), and worse chronic kidney disease (CKD) stage (P = .012). Kaplan-Meier curves revealed that patients with preoperative anemia had worse overall survival (OS), cancer-specific survival (CSS), and disease recurrence-free survival (RFS) (all P < .001). Multivariable Cox analyses found that anemia was an independent predictor of CSS [hazard ratio (HR) 1.719, 95% confidence interval (95% CI): 1.285-2.300], RFS (HR 1.427, 95% CI: 1.114-1.829) and OS (HR 1.756, 95% CI: 1.353-2.279). Among patients without end-stage renal disease (ESRD, n = 614), the anemia was also proved to be associated with worse outcomes in multivariable Cox analysis (OS, HR 1.759, 95% CI: 1.353-2.287; CSS, HR 1.726, 95% CI: 1.289-2.311, and RFS, HR 1.431, 95% CI: 1.117-1.837). Seven studies were included in the meta-analysis, and the pooled results showed that anemia was also related to worse CSS (HR 2.05, 95% CI: 1.73-2.44), RFS (HR 1.57, 95% CI: 1.30-1.90), and OS (HR 1.53, 95% CI: 1.10-2.13), but not related to intravesical recurrence (HR 1.17, 95% CI: 0.75-1.82).Preoperative anemia was proved to be significantly associated with worse oncologic outcomes in patients with UTUC following RNU.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000012300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155943PMC
September 2018

Is preoperative serum lactate dehydrogenase useful in predicting the outcomes of patients with upper tract urothelial carcinoma?

Cancer Med 2018 10 27;7(10):5096-5106. Epub 2018 Aug 27.

Department of Urology, West China Hospital, Sichuan University, Chengdu, China.

Background: Lactate dehydrogenase (LDH) has been proved to be associated with clinical outcomes in various carcinomas; however, limited evidence was available in upper urinary tract urothelial carcinoma (UTUC). Thus, the aim of this study was to evaluate the prognostic impact of LDH in UTUC.

Patients And Methods: A cohort of 668 patients WERE retrospectively included between 2003 and 2016. Kaplan-Meier method and Cox proportional hazards regression models were used to evaluate the association of LDH with overall survival (OS), cancer-specific survival (CSS), disease recurrence-free survival (RFS), and metastasis-free survival (MFS). The cutoff level of LDH was set at 220 U/L for the upper limit of normal.

Results: Kaplan-Meier plots showed the group with elevated LDH had significant poor OS (P = 0.003), CSS (P = 0.005), and RFS (P = 0.005), but not MFS (P = 0.099). However, multivariate Cox analysis suggested that LDH was not an independent predictor for CSS (HR 1.50, 95%CI: 0.87-2.59), OS (HR 1.56, 95%CI: 0.94-2.58), RFS (HR 1.33, 95%CI: 0.83-2.12), or MFS (HR 1.16, 95%CI: 0.79-1.71). Albumin, globulin, and HBDH were also not related to survival outcomes of UTUC patients in multivariate analysis, while higher alkaline phosphatase was associated with worse CSS and OS, and higher white blood cells contributed to poor CSS and RFS. In subgroup analysis, results found higher LDH was associated with poor OS in patients with localized disease (pT ≤ 2) (HR 4.03, 95%CI: 1.37-11.88).

Conclusion: The preoperative LDH was not an independent prognostic factor for patients with UTUC, while elevated LDH was proved to be correlated with worse OS in patients with localized disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.1751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198201PMC
October 2018

The prognostic significance of Albumin-to-Alkaline Phosphatase Ratio in upper tract urothelial carcinoma.

Sci Rep 2018 08 17;8(1):12311. Epub 2018 Aug 17.

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.

To assess the prognostic impact of pretreatment albumin-to-alkaline phosphatase ratio (AAPR) in patients with upper tract urothelial carcinoma (UTUC), the data of 692 patients, operated between 2003 and 2016 in our center, were retrospectively assessed. The threshold of AAPR was defined as 0.58 by using the receiver-operating curve analysis. Overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) were evaluated using the Kaplan-Meier method. And the univariate and multivariate Cox's regression models were performed to identify independent prognostic predictors. The results showed that AAPR <0.58 was significantly related to higher pT stage and grade, concomitant variant histology, anemia and larger tumor size. Additionally, patients with a lower AAPR had an inferior survival outcomes than those with an AAPR ≥0.58 (all P < 0.001). Multivariate analysis suggested that the lower AAPR was also an independent risk factor for poor OS (HR 1.587, 95%CI: 1.185-2.126; P = 0.002), CSS (HR 1.746, 95%CI: 1.249-2.440; P = 0.001), and RFS (HR 1.337, 95%CI: 1.027-1.739; P = 0.031). Moreover, subgroup analysis demonstrated the lower AAPR was related to worse prognosis in high-grade UTUC patients; but in those with low-grade disease, no relationship between them was observed. In conclusion, our results found that the decreased AAPR was independently related to poor survival outcomes in UTUC patients. Using the AAPR for subclassification of high-grade UTUC seems to further identify a poor prognostic group and contribute to clinical decisions making.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-29833-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097991PMC
August 2018

The prognostic value of preoperative neutrophil-to-lymphocyte ratio in patients with upper tract urothelial carcinoma.

Clin Chim Acta 2018 Oct 15;485:26-32. Epub 2018 Jun 15.

Department of Urology & Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China. Electronic address:

Background: We evaluated the prognostic impact of the preoperative neutrophil-to-lymphocyte ratio (NLR) in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy treatment.

Methods: A total of 717 patients were identified between 2003 and 2016. The cutoff value of NLR was set as 2.5. Kaplan-Meier method and Cox's proportional hazards regression models were utilized to analyze the association between NLR and oncological outcomes.

Results: The median follow-up was 42 months. The results suggested that preoperative elevated NLR was associated with worse pathological features. Also, patients with NLR ≥ 2.5 had worse survival outcomes than those with NLR <2.5 (all P < .001). Multivariate cox analysis revealed that NLR ≥ 2.5 was an independent predictor of worse cancer-specific survival, disease recurrence-free survival, metastasis-free survival and overall survival (HR 1.95, 95%CI: 1.42-2.69, P < .001; HR 1.70, 95%CI: 1.31-2.20, P < .001; HR 1.67, 95%CI: 1.22-2.31, P = .002; and HR 1.88, 95%CI: 1.42-2.50, P < .001; respectively). Notably, NLR was ascertained to be a useful prognostic predictor in patients with high-grade disease, but not in those with low-grade UTUC.

Conclusions: Preoperative elevated NLR was associated with worse outcomes in patients with UTUC. Subgroup analysis affirmed that NLR was a useful predictor in patients with high-grade disease, but not in those with low-grade UTUC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cca.2018.06.019DOI Listing
October 2018

Intra versus Inter Cross-resistance Determines Treatment Sequence between Taxane and AR-Targeting Therapies in Advanced Prostate Cancer.

Mol Cancer Ther 2018 10 11;17(10):2197-2205. Epub 2018 Jun 11.

Department of Urology, University of California, Davis, California.

Current treatments for castration resistant prostate cancer (CRPC) largely fall into two classes: androgen receptor (AR)-targeted therapies such as the next-generation antiandrogen therapies (NGAT), enzalutamide and abiraterone, and taxanes such as docetaxel and cabazitaxel. Despite improvements in outcomes, patients still succumb to the disease due to the development of resistance. Further complicating the situation is lack of a well-defined treatment sequence and potential for cross-resistance between therapies. We have developed several models representing CRPC with acquired therapeutic resistance. Here, we utilized these models to assess putative cross-resistance between treatments. We find that resistance to enzalutamide induces resistance to abiraterone and vice versa, but resistance to neither alters sensitivity to taxanes. Acquired resistance to docetaxel induces cross-resistance to cabazitaxel but not to enzalutamide or abiraterone. Correlating responses with known mechanisms of resistance indicates that AR variants are associated with resistance to NGATs, whereas the membrane efflux protein ABCB1 is associated with taxane resistance. Mechanistic studies show that AR variant-7 (AR-v7) is involved in NGAT resistance but not resistance to taxanes. Our findings suggest the existence of intra cross-resistance within a drug class (i.e., within NGATs or within taxanes), whereas inter cross-resistance between drug classes does not develop. Furthermore, our data suggest that resistance mechanisms differ between drug classes. These results may have clinical implications by showing that treatments of one class can be sequenced with those of another, but caution should be taken when sequencing similar classed drugs. In addition, the development and use of biomarkers indicating resistance will improve patient stratification for treatment. .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1535-7163.MCT-17-1269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168406PMC
October 2018

Diagnostic Ureteroscopy Prior to Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma Increased the Risk of Intravesical Recurrence.

Urol Int 2018 8;100(1):92-99. Epub 2017 Dec 8.

Department of Urology, West China Hospital, Sichuan University, Chengdu, China.

Objective: To assess the impact of diagnostic ureteroscopy (URS) prior to radical nephroureterectomy (RNU) on intravesical recurrence (IVR) in patients with upper tract urothelial carcinoma (UTUC).

Materials And Methods: A systematic literature search of the Medline, Embase, PubMed, and Cochrane library was performed in August 2017. Cumulative analyses of available hazard ratios (HRs) and their 95% CI were conducted using Stata version 12.0.

Results: Eleven studies including 4,057 participants were included, with a total of 1,403 patients diagnosed with IVR during the follow-up period. The pooled HRs of eight studies suggested that diagnostic URS prior to RNU significantly increased the IVR risk after RNU (HR 1.53, 95% CI 1.31-1.77; p < 0.001). However, the preoperative diagnostic URS was not associated with cancer-specific survival (HR 0.72; p = 0.11), metastasis-free survival (HR 1.09; p = 0.60) or overall survival (HR 1.12; p = 0.73). No publication bias was observed (Begg, p = 0.90; Egger, p = 0.71).

Conclusions: Regardless, the diagnostic URS prior to RNU might increase the IVR risk in patients with UTUC. As ureteroscopy provides important prognostic and therapeutic value and guides decisions in UTUC, more future studies should be performed to find a novel way to mitigate the potential risk of IVR after RNU, such as chemoprophylaxis after endoscopy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000484417DOI Listing
August 2018