Jae-Seung Chung

Preventive effects of cyclosporine a combined with prednisolone and melatonin on contralateral testicular damage after ipsilateral torsion-detorsion in pubertal and adult rats.

PURPOSE We compared the preventive effects of cyclosporine A combined with prednisolone and melatonin (Sigma-Aldrich) on damage to the contralateral testis after ipsilateral testicular torsion-detorsion between pubertal and adult rats. MATERIALS AND METHODS We divided pubertal and adult Sprague-Dawley rats into groups 1-sham operation, 2-detorsion, 3-detorsion plus cyclosporine A with prednisolone and 4-detorsion plus melatonin. After 4 hours of ipsilateral testicular torsion we treated the rats with detorsion only or with detorsion plus drug depending on the group. RESULTS Seminiferous tubule diameter and germ cell layer thickness were greater in pubertal group 3 and adult group 4 than at each age in group 2 (each p <0.05). The number of spermatids per tubule was greater in pubertal groups 3 and 4, and in adult group 4 than at each age in group 2 (each p <0.05). Of pubertal rats those in groups 3 and 4 had fewer TUNEL positive cells than group 2 (p = 0.061 and 0.057, respectively). Of adult rats the number of TUNEL positive cells was greater in group 3 and significantly lower in group 4 vs that in group 2 (p <0.05). CONCLUSIONS The preventive effects of cyclosporine A combined with prednisolone on contralateral testicular damage were noted only in pubertal rats while the preventive effects of melatonin were noted in pubertal and adult rats. Results suggest that damage to the contralateral testis induced by an immunological mechanism may be more significant during puberty than during adulthood.

Effectiveness of Intracavernous Delivery of Adenovirus Encoding Smad7 Gene on Erectile Function in a Mouse Model of Cavernous Nerve Injury

INTRODUCTION Men with erectile dysfunction (ED) respond poorly to oral phosphodiesterase-5 inhibitors following radical prostatectomy. Recent studies have reported that up-regulation of transforming growth factor-β1 (TGF-β1) and activation of the Smad signaling pathway play important roles in cavernous fibrosis and in the deterioration of erectile function in a mouse model of cavernous nerve injury (CNI) and in patients with spinal cord injury. The mothers against decapentaplegic homolog 7 (Smad7) is known to inhibit the phosphorylation of Smad2 and Smad3. AIM To investigate the effectiveness of adenoviruses encoding Smad7 gene (Ad-Smad7) on erectile function in a mouse model of CNI. METHODS Twelve-week-old C57BL/6J mice were used and distributed into 7 groups: sham operation group, untreated CNI group, and CNI groups receiving a single intracavernous injection of adenovirus encoding LacZ (1 × 10(8) virus particles [vp]/20 μL) or adenovirus encoding Smad7 (Ad-Smad7; 1 × 10(7), 1 × 10(8), 2 × 10(8), or 1 × 10(9) vp/20 μL). MAIN OUTCOME MEASURES Two weeks after bilateral cavernous nerve crushing and treatment, erectile function was measured by electrical stimulation of the cavernous nerve. The penis was harvested for histologic examinations and Western blot analysis. RESULTS The highest erectile response was noted in CNI mice treated with Ad-Smad7 at a dose of 1 × 10(8)  vp, which reached up to 82-85% of sham control values. Local delivery of Ad-Smad7 significantly decreased endothelial cell apoptosis and the production of extracellular matrix proteins, including plasminogen activator inhibitor-1, fibronectin, collagen I, and collagen IV, and induced endothelial nitric oxide synthase phosphorylation in the corpus cavernosum tissue of CNI mice. CONCLUSION The adenovirus-mediated gene transfer of Smad7 successfully restored erectile function by enhancing endothelial cell function and through antifibrotic effects. These findings suggest that inhibition of the TGF-β signaling pathway by use of Smad7 may represent a promising therapeutic strategy for ED induced by radical prostatectomy.

Simultaneous robotic low anterior resection and prostatectomy for adenocarcinoma of rectum and prostate: initial case report

BackgroundWe report a case of synchronous rectal and prostate cancer treated successfully with simultaneous da Vinci robotic-assisted low anterior resection of the rectum and robotic-assisted laparoscopic radical prostatectomy to address both cancers.Case presentationRecently, minimally invasive surgical techniques using da Vinci robot® system (Intuitive Surgical, Sunnyvale, USA) were introduced as curative surgical modality of prostate and rectal malignancies. Herein, we report an initial case of simultaneous robotic low anterior resection and robotic prostatectomy for adenocarcinoma of rectum and prostate sharing a considerable number of port sites.ConclusionSimultaneous robotic-assisted low anterior resection could be performed with robotic-assisted radical prostatectomy safely and effectively in synchronous rectal and prostate cancer.

Partial versus Radical Nephrectomy for T1-T2 Renal Cell Carcinoma in Patients with Chronic Kidney Disease Stage III: a Multiinstitutional Analysis of Kidney Function and Survival Rate

Background To examine survival rates and renal function after partial nephrectomy (PN) and radical nephrectomy (RN) in patients with chronic kidney disease (CKD). Methods We studied 4,332 patients who underwent PN or RN for pathological T1a-T2N0M0 renal cell carcinoma from 1988 to 2014. Patients were divided into two subgroups of CKD stage I–II and stage III. Kidney function, and survival outcomes were compared between groups. Results We included 1,756 patients with CKD I–II and 276 patients with CKD III in the final pair-matched analysis. Kidney function was significantly better preserved in the PN than in the RN group among all patients. However, the beneficial effect of PN on kidney function gradually disappeared over time in CKD III patients. The 5-year overall survival (OS) rates after PN and RN differed in patients with CKD I–II disease (99.4% vs. 96.5%, respectively, P = 0.015). The 5-year OS rates after surgery were not affected by mode of nephrectomy in CKD III patients (97.8% vs. 93.5%, P = 0.103). The 5-year cancer-specific survival rates did not differ between treatment groups in all CKD stage. Cox hazard analysis showed that the operative method was a significant factor for OS in CKD I–II patients (hazard ratio [HR], 0.320; confidence interval [CI], 0.122–0.840; P = 0.021). However, PN was not beneficial in terms of OS in CKD III patients (HR, 0.395; CI, 0.086–1.172; P = 0.117). Conclusion PN is associated with a higher OS rate and better kidney function in patients with preoperative CKD stage I and II, but not in those with CKD stage III.

PD71-06 CTC-BASED GENE EXPRESSION FOR PREDICTING RESISTANCE TO ABIRATERONE AND ENZALUTAMIDE IN MCRPC

prostate cancer, and compared it to a base model consisting of age, digital rectal exam findings, and PSA. Additionally, we compared the performance of the 4Kscore test in AA and non-AA men. RESULTS: Among 403 men who were enrolled in the trial, we had 366 men with a 4Kscore and complete data available for analysis. Among these men, 208 (56%) were AA, and 134 (36%) had G7+ prostate cancer. The 4Kscore exhibited better discrimination (AUC: 0.81 vs. 0.74, p1⁄40.011) and higher clinical utility on decision analysis than the base model for deciding on the need for biopsy. Calibration plots of the 4Kscore for the entire cohort afforded predictions that closely matched the observed risk of G7+ prostate cancer in the population (Figure 1). There was no difference in the discrimination of the 4Kscore test between AA and non-AA men (0.80 vs. 0.84; p1⁄40.32). While we found some evidence that the 4Kscore underestimates the risk of G7+ prostate cancer in AA men, discrimination (0.80 vs. 0.72, p 1⁄4 0.013) and clinical utility for the 4Kscore test were still higher than the base model. CONCLUSIONS: In an independent, multi-institutional, prospective trial of the 4Kscore test in the VA health system, we confirmed that the 4Kscore accurately predicts the likelihood of aggressive prostate cancer and outperforms standard clinical information for biopsy decision making in both AA and non-AA men.

PD71-07 GAS6, KLK2, AND BMP7 DETECTED IN CIRCULATING TUMOR CELLS PREDICT RESISTANCE TO CHEMOTHERAPY IN MCRPC

INTRODUCTION AND OBJECTIVES: Docetaxel or cabazitaxel-based chemotherapy continues to have a critical role in the treatment of men with metastatic castration-resistant prostate cancer (mCRPC). However, responses are heterogeneous and resistance to therapy is a pressing clinical problem. With the goal of developing liquid biomarkers to aid in treatment selection, we sought to identify genes associated with resistance to chemotherapy using a circulating tumor cell (CTC)-based approach. METHODS: Whole blood (~5mL) was obtained from 25 patients with mCRPC starting docetaxel (n1⁄421) or cabazitaxel (n1⁄44). CTCs were isolated using anti-EpCAM-conjugated magnetic beads, and following cell lysis, mRNA was extracted followed by multiplex qRTPCR for 44 prostate cancer-related genes plus internal controls. Gene expression was normalized to controls, and samples were considered CTC-positive based on a previously established set of epithelial markers (EpCAM, EGFR, DSG2, KRT8, KRT18 and KRT19). The primary endpoint was PSA progression-free survival (PFS), with PSA progression defined as an increase of 25% or more above the nadir. Univariable Cox regression analyses were performed to assess for genes associated with PFS at false discovery rate (FDR) < 0.20. RESULTS: Among 25 patients with mCRPC, we identified 84% (21/25) with detectable CTCs. The median age of the cohort was 62 years (IQR 58-70). At a median (IQR) follow up of 5.4 (3.4-9.3) months, 47.6 % (10/21) of patients showed a PSA decrease of at least 30% following treatment initiation. 18/21 patients (85.7%) experienced PSA progression at a median of 2.8 months (IQR 1.7-4.8). In the Cox analysis, KLK2 (HR 2.54, 95%CI 1.24-5.21, p1⁄40.011), GAS6 (HR 3.50, 95% CI 1.30-9.42, p1⁄40.013), and BMP7 (HR 2.01, 95%CI 1.15-3.52; p1⁄40.014) were associated with shorter PFS. CONCLUSIONS: Wehave identified three genes associatedwith progression in mCRPC patients initiating chemotherapy. While these early results need further confirmation, they suggest that CTCs may be utilized to help guide precision-based treatment strategies in patients with mCRPC. Additionally, these results corroborate our recent in vitro and in vivo findings (Lee et al, J Cell Biochem, 2016) indicating that GAS6 protects prostate cancer cells from docetaxel-induced apoptosis.