Impact of Circulating Tumor Cell-Expressed Prostate-Specific Membrane Antigen and Prostate-Specific Antigen Transcripts in Different Stages of Prostate Cancer.

PURPOSE: Prostate-specific membrane antigen (PSMA)-based images, which visually quantify PSMA expression, are used to determine prostate cancer micrometastases. This study evaluated whether a circulating tumor cell (CTC)-based transcript platform, including PSMA mRNA, could help identify potential prognostic markers in prostate cancer. EXPERIMENTAL DESIGN: We prospectively enrolled 21 healthy individuals and 247 patients with prostate cancer [localized prostate cancer (LPCa), n = 94; metastatic hormone-sensitive prostate cancer (mHSPC), n = 44; and metastatic castration-resistant prostate cancer (mCRPC), n = 109]. The mRNA expression of six transcripts [PSMA, prostate-specific antigen (PSA), AR, AR-V7, EpCAM, and KRT 19] from CTCs was measured, and their relationship with biochemical recurrence (BCR) in LPCa and mCRPC progression-free survival (PFS) rate in mHSPC was assessed. PSA-PFS and radiological-PFS were also calculated to identify potential biomarkers for predicting androgen receptor signaling inhibitor (ARSI) and taxane-based chemotherapy resistance in mCRPC. RESULTS: CTC detection rates were 75.5%, 95.3%, and 98.0% for LPCa, mHSPC, and mCRPC, respectively. In LPCa, PSMA [hazard ratio (HR), 3.35; P = 0.028) and PSA mRNA (HR, 1.42; P = 0.047] expressions were associated with BCR. Patients with mHSPC with high PSMA (HR, 4.26; P = 0.020) and PSA mRNA (HR, 3.52; P = 0.042) expressions showed significantly worse mCRPC-PFS rates than those with low expression. Increased PSA and PSMA mRNA expressions were significantly associated with shorter PSA-PFS and radiological PFS in mCPRC, indicating an association with drug resistance. CONCLUSIONS: PSMA and PSA mRNA expressions are associated with BCR in LPCa. In advanced prostate cancer, PSMA and PSA mRNA can also predict rapid progression from mHSPC to mCRPC and ARSI or taxane-based chemotherapy resistance.

Coexpression of lymphocyte-activation gene 3 and programmed death ligand-1 in tumor infiltrating immune cells predicts worse outcome in renal cell carcinoma.

OBJECTIVES: Lymphocyte-activation gene 3 (LAG-3) represents a potential immune checkpoint target for cancer treatment. We investigated LAG-3 expression and its prognostic value in patients with surgically treated clear cell renal cell carcinoma (RCC) and correlated LAG-3 expression with programmed cell death ligand 1(PD-L1). METHODS: We evaluated LAG-3 and PD-L1 expression using immunohistochemistry on tissue microarrays incorporating 134 primary excision specimens of clear cell RCC (ccRCC). The patients were analyzed as two groups: the whole cohort and those with metastatic RCC (mRCC). The cancer genome atlas (TCGA) data analysis of LAG-3 was done through UALCAN web servers. RESULTS: Using the UALCAN cancer transcriptional data analysis, we found that LAG-3 was overexpressed in ccRCC. LAG-3 expression was significantly correlated with PD-L1 expression in the whole cohort and in the mRCC group (all, p < 0.05). Both LAG-3⁺ RCC and PD-L1⁺ RCC presented with a higher TNM stage and higher Fuhrman nuclear grade (all, p < 0.05). PD-L1⁺/LAG-3⁺ RCC and PD-L1⁻/LAG-3⁺ RCC showed poorer cancer-specific survival (CSS) than PD-L1⁻/LAG-3⁻ RCC (all, p = 0.01). Similarly, PD-L1⁺/LAG-3⁺ mRCC and PD-L1⁻/LAG-3⁺ mRCC showed poorer CSS than PD-L1⁻/LAG-3⁻ mRCC (all, p < 0.05). Multivariate analysis showed that PD-L1⁺/LAG-3⁺ mRCC (hazard ratio: 3.19; 95% CI: 0.77-13.67; p = 0.033) was a predictor of poor CSS. CONCLUSION: Both LAG-3⁺ and PD-L1⁺ RCC have adverse pathological features, and their coexpression predicts worse clinical outcomes. Our findings suggest LAG-3 blockade in combination with programmed cell death 1/PD-L1 blockade as a potential therapeutic approach for RCC.

Expression of VISTA on tumor-infiltrating immune cells correlated with short intravesical recurrence in non-muscle-invasive bladder cancer.

V-domain immunoglobulin suppressor of T cell activation (VISTA) is an immune checkpoint molecule expressed in hematopoietic cells, granulocytes, macrophages, and monocytes. However, few studies to date have investigated VISTA expression, especially its clinical utility, in bladder cancer. The present retrospective study aimed to examine VISTA, programmed death ligand-1 (PD-L1), and CD45 expression by immunohistochemical and immunofluorescence staining of archived pathological tissue samples from 159 patients with primary bladder cancer. The correlation between VISTA expression in immune cells (ICs) and clinicopathologic variables including PD-L1 expression in ICs was examined. Briefly, the rates of VISTA-positive ICs and VISTA-positive tumor cells were 67.9% (108/159) and 30.8% (49/159), respectively. The VISTA expression in ICs of patients with bladder cancer, including those with non-muscle-invasive bladder cancer (NMIBC), was positively correlated with tumor stage, grade, size, and multiplicity. The VISTA expression in ICs was stronger in bladder cancer cases with PD-L1-positive ICs than in those with PD-L1-negative ICs (p < 0.001). The mean intravesical recurrence-free survival was shorter in NMIBC cases with VISTA-positive ICs than in those with VISTA-negative ICs (34.0 vs 39.9 months, p = 0.03, log-rank test). In this first study to investigate VISTA expression in bladder cancer, these results implicate VISTA as a potential immunotherapeutic target and immunologic biomarker in bladder cancer.

Targeted therapy response in early versus late recurrence of renal cell carcinoma after surgical treatment: A propensity score-matched study using the Korean Renal Cancer Study Group database.

OBJECTIVES: To investigate the clinicopathological features and outcomes of targeted therapy in patients with recurrence of renal cell carcinoma in <5 years or ≥5 years after the surgical treatment for renal cell carcinoma. METHODS: Patients with metastatic renal cell carcinoma treated with targeted therapy in a multicenter database were retrospectively characterized according to time from surgery to recurrence. Early recurrence was defined as recurrence within 5 years after surgery, and late recurrence was defined as occurring ≥5 years after surgery. The propensity scores for recurrence status were calculated, and patients with late recurrence were matched to patients with early recurrence at a 1:3 ratio. The oncological outcomes of targeted therapy in both groups were compared. RESULTS: Among 716 patients, 512 (71.5%) experienced early recurrence and 204 (28.5%) experienced late recurrence. The patients with late recurrence presented with younger age at surgery, lower tumor stages and Fuhrman grade, and fewer sarcomatoid features and lymphovascular invasion (all P < 0.005). All differences in clinicopathological characteristics before targeted therapy disappeared after matching. Patients with late recurrence had significantly longer median overall survival (56 months vs 36 months; P < 0.0001) and median first-line progression-free survival (12 months vs 8 months; P = 0.031). The early recurrence status was a significantly worse predictor for overall survival and first-line progression-free survival (hazard ratio 1.30, P = 0.007; and hazard ratio 1.76, P < 0.001, respectively). CONCLUSIONS: Late recurrence might have prognostic value in terms of oncological outcomes in metastatic renal cell carcinoma treated with targeted therapy.

Clinical factors that influence the occurrence of symptomatic pseudoaneurysms and arteriovenous fistulas after partial nephrectomy: multi-institutional study of renal function outcomes after one year of selective arterial embolization

ABSTRACT Purpose: Renal artery pseudoaneurysms (RAPs) and arteriovenous fistulas (AVFs) are rare but potentially life-threatening complications after partial nephrectomy (PN). Selective arterial embolization (SAE) is an effective method for controlling RAPs/AVFs. We assessed the clinical factors affecting the occurrence of RAPs/AVFs after PN and the effects of SAE on postsurgical renal function. Materials and Methods: Four hundred ninety-three patients who underwent PN were retrospectively reviewed. They were placed in either the SAE or the non-SAE group. The effects of clinical factors, including R.E.N.A.L. scores, on the occurrence of RAPs/AVFs were analyzed. The influence of SAE on the estimated glomerular filtration rate (eGFR) during the first postoperative year was evaluated. Results: Thirty-three (6.7%) patients experienced RAPs/AVFs within 8 days of the median interval between PN and SAE. The SAE group had significantly higher R.E.N.A.L. scores, higher N component scores, and higher L component scores (all, p <0.05). In the multivariate analysis, higher N component scores were associated with the occurrence of RAPs/AVFs (Odds ratio: 1.96, p=0.039). In the SAE group, the mean 3-day postembolization eGFR was significantly lower than the mean 3-day postoperative eGFR (p <0.01). This difference in the eGFRs was still present 1 year later. Conclusions: Renal tumors located near the renal sinus and collecting system were associated with a higher risk for RAPs/AVFs after PN. Although SAE was an effective method for controlling symptomatic RAPs/AVFs after PN, a procedure-related impairment of renal function after SAE could occur and still be present at the end of the first postoperative year.

Prognostic significance of sarcopenia and decreased relative dose intensity during the initial two cycles of first-line sunitinib for metastatic renal cell carcinoma.

Targeted therapy for metastatic renal cell carcinoma (mRCC) treatment requires the identification of clinically important factors that can predict the therapeutic effect. We retrospectively investigated the prognostic roles of pre-treatment sarcopenia and relative dose intensity during the initial two cycles (2c-RDI) of sunitinib treatment in patients with mRCC. In total, 41 (52.6%) patients were classified as having sarcopenia and 16 (20.5%) patients were classified with low 2c-RDI at <75%. The mean dose reduction during sunitinib treatment was higher for sarcopenic than for non-sarcopenic patients. The median progression-free survival (PFS) and overall survival (OS) were significantly shorter in sarcopenic patients with low 2c-RDI (n = 14, 17.9%) than in non-sarcopenic patients with high 2c-RDI (n = 35, 44.9%). Multivariate analysis identified sarcopenia and low 2c-RDI as poor prognostic factors for PFS and OS. Our findings provide new insights into the prognostic role of sarcopenia and 2c-RDI for targeted therapy in mRCC.

Multigene model for predicting metastatic prostate cancer using circulating tumor cells by microfluidic magnetophoresis.

We aimed to isolate circulating tumor cells (CTCs) using a microfluidic technique with a novel lateral magnetophoretic microseparator. Prostate cancer-specific gene expressions were evaluated using mRNA from the isolated CTCs. A CTC-based multigene model was then developed for identifying advanced prostate cancer. Peripheral blood samples were obtained from five healthy donors and patients with localized prostate cancer (26 cases), metastatic hormone-sensitive prostate cancer (mHSPC, 10 cases), and metastatic castration-resistant prostate cancer (mCRPC, 28 cases). CTC recovery rate and purity (enriched CTCs/total cells) were evaluated according to cancer stage. The areas under the curves of the six gene expressions were used to evaluate whether multigene models could identify mHSPC or mCRPC. The number of CTCs and their purity increased at more advanced cancer stages. In mHSPC/mCRPC cases, the specimens had an average of 27.5 CTCs/mL blood, which was 4.2 × higher than the isolation rate for localized disease. The CTC purity increased from 2.1% for localized disease to 3.8% for mHSPC and 6.7% for mCRPC, with increased CTC expression of the genes encoding prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), and cytokeratin 19 (KRT19). All disease stages exhibited expression of the genes encoding androgen receptor (AR) and epithelial cell adhesion molecule (EpCAM), although expression of the AR-V7 variant was relatively rare. Relative to each gene alone, the multigene model had better accuracy for predicting advanced prostate cancer. Our lateral magnetophoretic microseparator can be used for identifying prostate cancer biomarkers. In addition, CTC-based genetic signatures may guide the early diagnosis of advanced prostate cancer.

Clinical factors that influence the occurrence of symptomatic pseudoaneurysms and arteriovenous fistulas after partial nephrectomy: multi-institutional study of renal function outcomes after one year of selective arterial embolization.

PURPOSE: Renal artery pseudoaneurysms (RAPs) and arteriovenous fistulas (AVFs) are rare but potentially life-threatening complications after partial nephrectomy (PN). Selective arterial embolization (SAE) is an effective method for controlling RAPs/AVFs. We assessed the clinical factors affecting the occurrence of RAPs/AVFs after PN and the effects of SAE on postsurgical renal function. MATERIALS AND METHODS: Four hundred ninety-three patients who underwent PN were retrospectively reviewed. They were placed in either the SAE or the non-SAE group. The effects of clinical factors, including R.E.N.A.L. scores, on the occurrence of RAPs/AVFs were analyzed. The influence of SAE on the estimated glomerular filtration rate (eGFR) during the first postoperative year was evaluated. RESULTS: Thirty-three (6.7%) patients experienced RAPs/AVFs within 8 days of the median interval between PN and SAE. The SAE group had significantly higher R.E.N.A.L. scores, higher N component scores, and higher L component scores (all, p <0.05). In the multivariate analysis, higher N component scores were associated with the occurrence of RAPs/AVFs (Odds ratio: 1.96, p=0.039). In the SAE group, the mean 3-day postembolization eGFR was significantly lower than the mean 3-day postoperative eGFR (p <0.01). This difference in the eGFRs was still present 1 year later. CONCLUSIONS: Renal tumors located near the renal sinus and collecting system were associated with a higher risk for RAPs/AVFs after PN. Although SAE was an effective method for controlling symptomatic RAPs/AVFs after PN, a procedure-related impairment of renal function after SAE could occur and still be present at the end of the first postoperative year.

Role of Prior Split Renal Function for Living Kidney Transplantation in Recipients and Donors.

PURPOSE: The purpose of this study was to determine the relationship between pre-operative donor split renal function (SRF) and the renal function outcome of donors and recipients after kidney transplantation (KT). METHODS: A total of 217 living KT cases were investigated. The estimated glomerular filtration rate (eGFR) change of recipients and donors, as well as graft survival, were analyzed based on the donor SRF. The difference in SRF (dSRF) in a donor was defined as follows: the SRF of the donated kidney minus the SRF of the remaining kidney determined by pre-operative 99mTc-diethylenetriaminepentaacetic acid in the donors. The dSRF was categorized into tertiles. RESULTS: The dSRF was not associated with the eGFR in recipients in any tertile at 6 or 12 months post-KT. The overall graft and patient survival did not differ significantly among tertiles. Donors in the high tertile, who donated kidneys with a higher SRF, showed a greater reduction in eGFR than did donors in the low and middle tertile after adjustment for function of the not-donated kidney (-34 ± 1.9 vs -28 ± 2.2, and -27 ± 1.3 mL/min/1.73 m2, P < .05). CONCLUSIONS: The dSRF did not affect the post-KT renal function or graft survival in recipients. However, the donors who donated the better functioning kidney had a poorer renal function after donation.

Effect of 5α-reductase inhibitors on the efficiency of thulium:yttrium-aluminium-garnet (RevoLix®) vaporesection for treating benign prostatic hyperplasia.

Purpose: Preoperative use of 5α-reductase inhibitors (5ARIs) may cause fibrosis of the prostate tissue and reduce the efficiency of thulium laser surgery for treating benign prostate hyperplasia (BPH). Thus, we investigated the effects of preoperative 5ARI use in this setting. Materials and Methods: This retrospective study examined 184 patients who underwent thulium laser surgery for BPH during 2012-2017. Patients were grouped according to their 5ARI use in order to compare their preoperative and intraoperative characteristics and subsequent outcomes. Surgical efficiency was assessed using vaporesection efficiency. The total operation time, vaporesection time and prostate volume change were measured. Results: The 5ARI+ group included 83 patients (45.1%) and the 5ARI- group included 101 patients (54.9%). There were no significant differences in the two groups' preoperative characteristics, postoperative prostate size, thulium laser energy use, or prostate volume reduction rate. However, relative to the 5ARI- group, the 5ARI+ group had a significant shorter total operative time (65.0 min vs. 70.0 min, p=0.013) and a significantly shorter vaporesection time (48.0 min vs. 54.0 min, p=0.014), which resulted in significantly higher vaporesection efficiency in the 5ARI+ group (0.66 mL/min vs. 0.51 mL/min, p<0.001). Both groups exhibit significant improvements in their quality of life score and International Prostate Symptom Score during the 12-month follow-up. Conclusions: In contrast with our expectations, the preoperative use of 5ARI increased the efficiency of thulium laser surgery for BPH. Thus, it may not be necessary to stop 5ARI treatment before performing thulium laser surgery in this setting.

Effect of Converting From Calcineurin Inhibitor- to Sirolimus-Based Immunosuppressant Regimen on Breast Fibroadenoma Among Kidney Transplant Patients.

The incidence rate of breast fibroadenomas is higher among female kidney transplant (KT) patients treated using cyclosporine (CsA) for immunosuppression than in the general population. As such, there is an effort to convert immunosuppression from CsA or tacrolimus to sirolimus. Our aim was to assess the reversibility of a breast fibroadenoma after conversion in a small cohort of female KT recipients. This was an open-label, single-arm study including 128 female KT recipients, with a positive finding of a breast fibroadenoma in 15. Lesions were classified according to the Breast Imaging Reporting and Data System (BIRADS). Among these 15, a total of 7 converted from tacrolimus to sirolimus and 8 converted from CsA. We measured the change in BIRADS category and hormone and cytokine levels from baseline to 12 months after conversion. The primary outcome was progression or reversal of existing fibroadenomas at 12 months after conversion. Secondary outcomes were differences in hormone and cytokine levels. Conversion from CsA or tacrolimus to sirolimus had no significant effect on the BIRADS classification. However, conversion to sirolimus did produce a significant decrease in the level of transforming growth factor ß cytokine, this level being closely associated with fibroadenomas. Conversion from a calcineurin inhibitor to sirolimus can block the progression of fibroadenomas. Further research is needed to confirm our results.

The superiority of contact surface area as a predictor of renal cortical volume change after partial nephrectomy compared to RENAL, PADUA and C-index: an approach using computed tomography-based renal volumetry.

Objective: To evaluate the renal cortical volume (RCV) change after nephron sparing surgery and the predictive value of the nephrometry score in RCV preservation after partial nephrectomy. Materials and methods: Overall, 162 patients with renal tumors that were treated with open partial nephrectomy were retrospectively analyzed. The contact surface area (CSA), RENAL, PADUA and C-index scores were obtained from a preoperative CT scan. The RCV of the tumor-bearing kidney was measured preoperatively and postoperatively using dedicated software. The correlation between the four nephrometry scores and perioperative parameters were evaluated and the scores were compared in terms of their ability to predict a reduction in the RCV. Results: All scores showed a significant association with reduction in RCV (all p < 0.001), percent reduction in RCV (all p < 0.001) and estimated blood loss (all p < 0.05). Only the CSA and PADUA scores showed a significant association with percent reduction in eGFR (p = 0.038 and p = 0.026, respectively). On multivariate analysis, the CSA, PADUA and C-index scores independently affected the percent reduction in RCV (p = 0.003, p = 0.025 and p = 0.013, respectively). On ROC curve analysis, CSA was a better independent predictor of a greater than 10% and 20% reduction in the RCV (AUC 0.87 and 0.72, respectively). Conclusion: CT-based RCV measurement successfully differentiated the RCV change after partial nephrectomy. Compared to the other three nephrometry scores, CSA was a superior predictor of RCV change in the operated kidney.

Correlation between 5-α reductase type 2 protein expression and methylation of 5-α reductase type 2 promotor gene of benign prostatic hyperplasia.

PURPOSE: The enzyme 5-α reductase type 2 (5-AR 2) plays a key role in the development and maintenance of the prostate gland. We evaluated the level 5-AR 2 protein expression and the relationship between methylation of the 5-AR 2 gene-promoter and 5-AR 2 protein expression of benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A total of 37 prostate samples were evaluated. These included 22 samples from men undergoing transurethral prostate resections and 15 non-cancerous transition-zone human prostate tissue samples taken following radical prostatectomy. We quantified 5-AR 2 protein expression and gene-promoter methylation status using common assay procedures. Clinical variables included age, body mass index (BMI), prostate-specific antigen (PSA) levels, lipid profiles, and prostate volumes. Univariate and multivariate statistical analyses were performed followed by stepwise logistic regression modeling. RESULTS: We were able to extract DNA from 36 of the 37 tissue samples and 10 of these (28%) did not express the 5-AR 2 protein. In total, 26 patients (72%) had methylated 5-AR 2 promoter-regions. There was a strong correlation between methylation of the 5-AR 2 promoter-regions and low-absent 5-AR 2 protein expression (p = 0.0003). Increasing age significantly predicted methylation status and protein expression level (p = 0.013). CONCLUSIONS: The level of 5-AR 2 protein expression varies among prostate tissue samples. Methylation of the 5-AR 2 gene-promoter may account for low or absent expression of 5-AR 2 in adult human prostate tissues. Increased age correlates with increased 5-AR 2 gene-promoter methylation and decreased protein expression in men with BPH.

Laparoscopic -2port Varicocelectomy with Scarless Periumblical Mini-Incision: Initial Experience in Approach and Outcomes.

PURPOSE: As with other areas, there have been many efforts for minimally invasive surgery in varicocelectomy. We present our initial experience with laparoscopic varicocelectomy with a two-port scarless periumbilical mini-incision. MATERIALS AND METHODS: The study enrolled 18 patients who underwent laparoscopic varicocelectomy with a twoportscarless periumbilical mini-incision from February 2012 to April 2013. The laparoscopic varicocelectomy was performed using two 5-mm ports at periumbilical sites in skin creases. Here, the surgical procedure is introduced and the outcomes of the case series are summarized. We reviewed other laparoscopic techniques and compared them with our technique. RESULTS: The mean patient age was 34.8 years. Of the 18 patients, 15 had grade 3 varicoceles. The mean operatingtime was 62.5 minutes. Postoperatively, the scrotal pain level decreased immediately from a mean VAS score of 6.3 to 4.4 and then to 1.7 by 24 hours postoperatively. The mean hospital stay was 2.8 days. Complications included one hydrocele and two recurrent varicoceles. The operating time decreased as the surgeon's experience increased. CONCLUSION: Laparoscopic varicocelectomy with a two-port scarless periumbilical mini-incision is a feasible technique that can be mastered relatively easily. Prospective and comparative studies are required to validate this new technique.

Longitudinal changes in erectile function after thulium:YAG prostatectomy for the treatment of benign prostatic obstruction: a 1-year follow-up study.

This study aimed to evaluate the impact of thulium:yttrium-aluminum-garnet (Tm:YAG) (RevoLix®) laser prostatectomy for the treatment of benign prostatic obstructions on erectile function (EF). A total of 208 patients who underwent Tm:YAG laser prostatectomies participated in this study. All cases were evaluated preoperatively and at 3, 6, and 12 months postoperatively using the International Prostate Symptom Score (IPSS), quality of life (QoL) score, and the International Index of Erectile Function (IIEF-5) questionnaires. Patients were divided into groups A (severe erectile dysfunction [ED]), B (moderate ED), and C (mild-to-normal ED), according to their IIEF-5 scores. The median patient ages were 69, 65, and 62 years in groups A, B, and C, respectively. Significant improvements occurred in the IPSS and QoL score within the groups during the 12-month follow-up period. The IIEF-5 scores at 3 months postoperatively were lower than the preoperative scores in groups B and C. The IIEF-5 scores subsequently improved during the 12-month follow-up period. The slope of the relationship between the IIEF-5 score and the time since Tm:YAG laser prostatectomy had a ß value of 0.2210 (95% confidence interval 0.103 to 0.338, p = 0.0003); hence, each postoperative month was associated with an increase of 0.2210 in the IIEF-5 score. The IIEF-5 scores gradually increased and reached the preoperative levels by the 12-month follow-up assessment. Although the IIEF-5 score dropped significantly during the first 3 months postoperatively, it improved over the following 12 months. Tm:YAG laser prostatectomy did not impact on EF ultimately.

Correlation between postoperative prostate-specific antigen and biochemical recurrence in positive surgical margin patients: Single surgeon series.

BACKGROUND: To evaluate the relationship between postoperative prostate-specific antigen (PSA) levels and biochemical recurrence (BCR) after radical prostatectomy, especially in patients with positive surgical margins (PSMs). MATERIALS AND METHODS: A total of 144 patients who underwent radical prostatectomies performed by a single surgeon without any neoadjuvant or adjuvant treatment were analyzed. Differences in clinicopathological factors were compared by surgical margin status, and the relationship between postoperative PSA level and BCR in patients with PSMs was evaluated. RESULTS: Fifty of the 144 patients (34.7%) had PSMs. Of these, 74% experienced BCR. The negative surgical margins and PSMs groups differed significantly in terms of PSA level at diagnosis, clinical T stage, and risk group by the cancer of the prostate risk assessment score (P = 0.002, P = 0.002, and P = 0.004, respectively). Also, the nadir PSA level, tumor volume, and BCR rate differed between the two groups (P = 0.007, P = 0.015, and P = 0.005, respectively) On Kaplan-Meier analysis, BCR-free survival was better in the negative surgical margins than the PSMs group (64.1 vs. 55.4 months, log-rank test, P = 0.011). BCR-free survival did not differ significantly in PSMs patients according to whether PSA level was or was not detectable at 1 month postoperatively. However, BCR-free survival improved when the nadir PSA level was undetectable (compared to detectable) in PSMs patients (64.3 vs. 26.1 months, log-rank test, P < 0.001). In PSMs patients belonging to the high risk group by cancer of the prostate risk assessment score, BCR-free survival was significantly better when the PSA level attained the nadir within 3 months, compared to > 6 months, postoperatively (64.2 vs. 29.5 months, log-rank test, P = 0.022). CONCLUSION: If PSA is detectable in PSMs patients until 1 month after operation, cautious observation may be possible. If the nadir is attained within 3 months postoperatively in high-risk patients with PSMs, better BCR-free survival may be expected.

Wnt signaling promotes androgen-independent prostate cancer cell proliferation through up-regulation of the hippo pathway effector YAP.

Aberrant up-regulation of Wnt/ß-catenin signaling is associated with the development and progression of prostate cancer, but the underlying mechanism is unclear. Here we show that in the absence of androgens, the Wnt/ß-catenin pathway activates AR-mediated transcription through up-regulation of the Hippo pathway effector Yes-associated protein (YAP). Wnt3a-conditioned medium (Wnt3a-CM) promotes the growth of LNCaP cells and increases AR and YAP protein levels. Moreover, Wnt3a-CM induces the nuclear translocation of YAP and the AR, but not ß-catenin, thereby activating the expression of AR- and YAP-dependent genes, in an androgen-independent manner. In addition, depletion of YAP with small interfering RNA (siRNA) prevented Wnt3a-CM-mediated up-regulation of AR-dependent gene expression. Thus, our findings provide mechanistic insight into the proposed cross-talk between the Wnt/ß-catenin and Hippo pathways in androgen-independent prostate cancer development.

Transutricular seminal vesiculoscopy in the management of symptomatic midline cyst of the prostate.

PURPOSE: To evaluate the utility of transutricular seminal vesiculoscopy as a diagnostic and therapeutic option for symptomatic midline cyst of the prostate in patients with hematospermia and symptoms associated with prostatitis. MATERIALS AND METHODS: From January 2005 to July 2013, 61 patients with symptomatic (hematospermia, pain on ejaculation, scrotal discomfort) midline cyst of the prostate, who did not improve with medication within a 4-week period, were included. Diagnosis of a midline cyst of the prostate was based on an anechoic round or spheroid-shaped lesion in the median, above the level of the verumontanum, extending into the prostatic base on transrectal ultrasonography (TRUS). All patients underwent transutricular seminal vesiculoscopy using a 9.0 Fr rigid ureteroscope and Bugbee electrode. Medical records, the Chronic Prostatitis Symptom Index (NIH-CPSI), and TRUS were used for assessment for more than 3 months after the procedure. RESULTS: Of the 61 patients, 32 (52.4 %) had hematospermia, 20 (32.7 %) had symptoms associated with chronic pelvic pain syndrome, such as perineal pain, scrotal discomfort, and testicular pain, and nine (14.7 %) patients had ejaculatory disturbances, such as painful or uncomfortable ejaculation and anejaculation as major complaints/symptoms. In endoscopic findings, hemorrhage was present in the dilation of the prostatic utricle and in the seminal vesicle in 11 (18.0 %) and 21 (34.4 %) of the patients, respectively. Calculi were found in the dilation of the prostatic utricle and in the seminal vesicle in 12 (19.7 %) and six (9.8 %), respectively. Hematospermia resolved in 29 of 32 (90.6 %) patients after transutricular seminal vesiculoscopy. In 29 patients with chronic pelvic pain syndrome and ejaculatory disturbances, NIH-CPSI scores improved, from 19.0 ± 3.8 to 11.8 ± 3.6 (p < 0.001), after treatment. The pain domain and quality-of-life domain scores of the NIH-CPSI were better postsurgery than presurgery (p < 0.001). Acute epididymitis, as a postoperative complication, was observed in two patients (3.3 %). CONCLUSIONS: There are various endoscopic findings in the dilation of prostatic utricle and seminal vesicle such as hemorrhage, calculi or/and purulent material in the patients with midline cyst of the prostate. The role of transutricular seminal vesiculoscopy in reducing symptoms may be mediated through the effects of endoscopic fenestration, removal of blood clots, calculi, or whitish debris and/or electrocautery of intracystic hemorrhage. This endoscopic technique enables useful diagnostic and therapeutic approaches for symptomatic midline cysts of the prostate.

Incidental abnormal FDG uptake in the prostate on 18-fluoro-2-deoxyglucose positron emission tomography-computed tomography scans.

18-fluoro-2-deoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) scans are commonly used for the staging and restaging of various malignancies, such as head and neck, breast, colorectal and gynecological cancers. However, the value of FDG PET/CT for detecting prostate cancer is unknown. The aim of this study was to evaluate the clinical value of incidental prostate 18F-FDG uptake on PET/CT scans. We reviewed 18F-FDG PET/CT scan reports from September 2009 to September 2013, and selected cases that reported focal/diffuse FDG uptake in the prostate. We analyzed the correlation between 18F-FDG PET/CT scan findings and data collected during evaluations such as serum prostate-specific antigen (PSA) levels, digital rectal examination (DRE), transrectal ultrasound (TRUS), and/or biopsy to confirm prostate cancer. Of a total of 18,393 cases, 106 (0.6%) exhibited abnormal hypermetabolism in the prostate. Additional evaluations were performed in 66 patients. Serum PSA levels were not significantly correlated with maximum standardized uptake values (SUVmax) in all patients (rho 0.483, p=0.132). Prostate biopsies were performed in 15 patients, and prostate cancer was confirmed in 11. The median serum PSA level was 4.8 (0.55-7.06) ng/mL and 127.4 (1.06-495) ng/mL in the benign and prostate cancer groups, respectively. The median SUVmax was higher in the prostate cancer group (mean 10.1, range 3.8-24.5) than in the benign group (mean 4.3, range 3.1-8.8), but the difference was not statistically significant (p=0.078). There was no significant correlation between SUVmax and serum PSA, prostatic volume, or Gleason score. 18F-FDG PET/CT scans did not reliably differentiate malignant or benign from abnormal uptake lesions in the prostate, and routine prostate biopsy was not usually recommended in patients with abnormal FDG uptake. Nevertheless, patients with incidental prostate uptake on 18F-FDG PET/ CT scans should not be ignored and should be undergo further clinical evaluations, such as PSA and DRE.

Cancer of the Prostate Risk Assessment (CAPRA) Preoperative Score Versus Postoperative Score (CAPRA-S): ability to predict cancer progression and decision-making regarding adjuvant therapy after radical prostatectomy.

The University of California, San Francisco, announced in 2011 Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score which included pathologic data, but there were no results for comparing preoperative predictors with the CAPRA-S score. We evaluated the validation of the CAPRA-S score in our institution and compare the result with the preoperative progression predictor, CAPRA score. Data of 130 patients were reviewed who underwent radical prostatectomy for localized prostate cancer from 2008 to 2013. Performance of CAPRA-S score in predicting progression free probabilities was assessed through Kaplan Meier analysis and Cox proportional hazards regression test. Additionally, prediction probability was compared with preoperative CAPRA score by logistic regression analysis. Comparing CAPRA score, the CAPRA-S score showed improved prediction ability for 5 yr progression free survival (concordance index 0.80, P = 0.04). After risk group stratification, 3 group model of CAPRA-S was superior than 3 group model of CAPRA for 3-yr progression free survival and 5-yr progression free survival (concordance index 0.74 vs. 0.70, 0.77 vs. 0.71, P < 0.001). Finally the CAPRA-S score was the more ideal predictor concerned with adjuvant therapy than the CAPRA score through decision curve analysis. The CPARA-S score is a useful predictor for disease progression after radical prostatectomy.