Christopher Han

Neutrophil and Lymphocyte Counts as Clinical Markers for Stratifying Low-Risk Prostate Cancer

UNLABELLED Appropriate patient selection for active surveillance is challenging.Our study of 217 patients demonstrated that the preoperative absolute neutrophil and lymphocyte counts were better predictors of aggressive oncologic features than were the neutrophil-to-lymphocyte ratio in the assessment of low-risk prostate cancer patients. Our findings suggest that routine hematologic workup could be used to further stratify low-risk prostate cancer patients. INTRODUCTION The neutrophil-to-lymphocyte ratio (NLR) has emerged as a ubiquitous prognostic biomarker in cancer-related inflammation, specifically in patients with metastatic castration-resistant prostate cancer (PCa). We evaluated the clinical utility of the preoperative NLR, absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) as a risk stratification tool for patients with low-risk PCa. MATERIALS AND METHODS We identified 217 low-risk PCa patients with preoperative hematologic data who had met the criteria for active surveillance but had undergone robot-assisted radical prostatectomy at our institution from 2006 to 2015. Logistic regression models were constructed to determine whether the baseline NLR, ANC, and ALC were associated with upstaging, upgrading, and biochemical recurrence (BCR). Survival analyses were performed using the Kaplan-Meier method. RESULTS On multivariate analysis, a higher prostate-specific antigen level (odds ratio [OR], 1.554; 95% confidence interval [CI], 1.148-2.104), a greater number of positive cores (OR, 2.098; 95% CI, 1.043-2.104), and a higher ALC (OR, 4.311; 95% CI, 1.258-14.770) were associated with upstaging. More importantly, the 5-year biochemical recurrence-free survival was significantly lower in the high ANC group (ANC > 4.0 × 10(9)/L) compared with that of the low ANC group (P = .011). The NLR was not associated with upstaging, upgrading, or BCR in our study cohort (P = .368, P = .573, and P = .504, respectively). The only significant association with upgrading was patient age (OR, 1.106; 95% CI, 1.043-1.173). CONCLUSION NLR was not useful in predicting adverse pathologic outcomes in our patients with low-risk PCa. However, relative neutrophilia and lymphocytosis might indicate an early manifestation of harboring a more aggressive PCa.

Pharmacokinetics, pharmacodynamics and clinical efficacy of abiraterone acetate for treating metastatic castration-resistant prostate cancer

Introduction: Androgen signaling axis (ASA) continues to play a crucial role in castration-resistant prostate cancer (CRPC). One of the proposed mechanisms is the activation of ASA by adrenal and intratumoral androgens. Targeted therapy to deplete such androgen sources should be effective in treating men with CRPC. Areas covered: Abiraterone acetate (AA) is a selective irreversible inhibitor of CYP 17. It is orally administered and is converted to its active metabolite abiraterone by the liver. Increased adrenocorticotrophic hormone drive, however, results in increased risks of hypertension and hypokalemia. In Phase III trials, AA with prednisone was shown to improve survivals in men with metastatic CRPC (mCRPC). The overall tolerability and safety profiles were acceptable. Expert opinion: It is now accepted that CRPC is not independent of androgen signaling, and targeted therapies to suppress ASA have recently been developed. With multiple high-level evidences of efficacy and safety, AA is considered a breakthrough in the treatment of mCRPC. Current clinical challenge, however, is to better delineate the mechanisms of the disease progression for developments of resistance to targeted therapies. Identification of the drug-resistance patterns would allow better patient selection for each treatment modality.

Comparison of Urinary Tract Infection Rates Associated with Transurethral Catheterization, Suprapubic Tube and Clean Intermittent Catheterization in the Postoperative Setting: A Network Meta-Analysis

Purpose: We performed a network meta‐analysis of available randomized, controlled trials to elucidate the risks of urinary tract infection associated with transurethral catheterization, suprapubic tubes and intermittent catheterization in the postoperative setting. Materials and Methods: PubMed®, EMBASE® and Google Scholar™ searches were performed for eligible randomized, controlled trials from January 1980 to July 2015 that included patients who underwent transurethral catheterization, suprapubic tube placement or intermittent catheterization at the time of surgery and catheterization lasting up to postoperative day 30. The primary outcome of comparison was the urinary tract infection rate via a network meta‐analysis with random effects model using the netmeta package in R 3.2 (www.r‐project.org/). Results: Included in analysis were 14 randomized, controlled trials in a total of 1,391 patients. Intermittent catheterization and suprapubic tubes showed no evidence of decreased urinary tract infection rates compared to transurethral catheterization. Suprapubic tubes and intermittent catheterization had comparable urinary tract infection rates (OR 0.903, 95% CI 0.479–2.555). On subgroup analysis of 10 randomized, controlled trials with available mean catheterization duration data in a total of 928 patients intermittent catheterization and suprapubic tube were associated with significantly decreased risk of urinary tract infection compared to transurethral catheterization when catheterization duration was greater than 5 days (OR 0.173, 95% CI 0.073–0.412 and OR 0.142, 95% CI 0.073–0.276, respectively). Conclusions: Transurethral catheterization is not associated with an increased urinary tract infection risk compared to suprapubic tubes and intermittent catheterization if catheterization duration is 5 days or less. However, a suprapubic tube or intermittent catheterization is associated with a lower rate of urinary tract infection if longer term catheterization is expected in the postoperative period.

Intracrine androgen biosynthesis in renal cell carcinoma

Background:Renal cell carcinoma (RCC) is one of the most lethal genitourinary cancers. The presence of androgen receptor (AR) in RCC has recently been shown to be associated with higher tumour stage irrespective of gender. Because the clinical context of androgens in female RCC patients is similar to that of prostate cancer patients undergoing androgen-deprivation therapy, mechanisms underlying the emergence of castration-resistant prostate cancer (CRPC) may be at play in AR-positive RCC cells. Therefore, we hypothesized that AR-positive RCC has intratumoral steroidogenesis and that anti-androgen therapy may result in tumour suppression.Methods:Mice were injected with an AR-positive RCC cell line. When tumours became palpable, surgical castration was performed and tumour volume was measured. Using ELISA, the levels of intracellular testosterone and dihydrotesterone were measured in AR-positive human RCC cell lines. Lastly, male mice containing xenografts were treated with enzalutamide or abiraterone acetate (AA) for 3 weeks to measure tumour volume.Results:We first observed in vivo that castration retards the growth of AR-positive RCC tumour xenograft in mice. Next, AR-positive human RCC cell lines and tissues were found to have elevated levels of testosterone and dihydrotestosterone and express key enzymes required for intracellular androgen biosynthesis. A mouse xenograft study with AR-positive RCC cell line using the commonly used anti-androgen therapies showed significant tumour suppression (P<0.01).Conclusions:Intracrine androgen biosynthesis is a potential source of androgen in AR-positive RCC and that the androgen signaling axis is a potential target of intervention in RCC.

MP60-08 INTRACRINE ANDROGEN BIOSYNTHESIS IN RENAL CELL CARCINOMA

INTRODUCTION AND OBJECTIVES: We previously reported that high MET and matriptase expression in RCC cells in bone metastasis indicates their importance in bone metastasis (Mukai et al. Hum Cell, 2015). MET is a high-affinity receptor tyrosine kinase of hepatocyte growth factor (HGF). HGF is secreted as an inactive singlechain precursor, which requires proteolytic activation for conversion to an active form. Matriptase is the most efficient known cellular activator of pro-HGF. Furthermore, activation of matriptase is regulated by HGF activator inhibitor (HAI). In this study, we employed a previously reported mouse model of bone metastasis (Strube et al. Clin Exp Metastasis, 2010) to clarify the significance of the matriptase-induced HGF/MET signaling axis in RCC bone metastasis. METHODS: Luciferase-transfected 786-O cells were injected into the left cardiac ventricle of female nude mice (5 weeks old). After 6 weeks, we confirmed the formation of bone metastasis by whole-body bioluminescent imaging, and extracted specimens. Expression of matriptase, MET and HAI was analyzed by PCR, immunohistochemistry (IHC) and immunoblots. Phosphorylation of MET was also investigated. Based on the result, we produced HAI-2 (specific inhibitor of matriptase) stable knock down (KD) 786-O cells, and analyzed the difference of expression in each molecule, cell-migration assay and invasion assay. RESULTS: Expression of matriptase was increased significantly in bone metastasis compared with parent cell line, and we confirmed increased phosphorylation of MET in bone metastasis. On the other hand, decreased expression of HAI-2 was observed in bone metastasis. Interestingly, increased matriptase expression was observed by HAI-2 KD in 786-O cells. In addition, invasive activity was increased significantly by knock down of HAI-2. CONCLUSIONS: These results have suggested that matriptase contributes to the HGF-dependent MET activation in the pericellular microenvironment of bone metastasis in RCC. In addition, upregulation of matriptase and downregulation of HAI-2 may have important roles in their progression.

MP75-18 COMPARISON OF COSTS AND OUTCOMES OF PERCUTANEOUS NEPHROLITHOTOMY BASED ON PERCUTANEOUS ACCESS

1 symptomatic ipsilateral pleural effusion requiring thoracocentesis. Other complications occurred in 9 patients (11.8%) which included bleeding requiring transfusion (1), fever (4), urinary retention (2), and syncope (2). CONCLUSIONS: Compared to historical controls, our approach to upper tract PCNL utilizing a nephrostomy tube free approach resulted in an overall low thoracic complication rate and facilitated hospital discharge.

Laparoscopic partial nephrectomy: state of the art review

License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php Open Access Surgery 2014:7 59–69 Open Access Surgery Dovepress