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.

Effective Circulating Tumor Cell Isolation Using Epithelial and Mesenchymal Markers in Prostate and Pancreatic Cancer Patients.

Circulating tumor cells (CTCs) display antigenic heterogeneity between epithelial and mesenchymal phenotypes. However, most current CTC isolation methods rely on EpCAM (epithelial cell adhesion molecule) antibodies. This study introduces a more efficient CTC isolation technique utilizing both EpCAM and vimentin (mesenchymal cell marker) antibodies, alongside a lateral magnetophoretic microseparator. The effectiveness of this approach was assessed by isolating CTCs from prostate (n = 17) and pancreatic (n = 5) cancer patients using EpCAM alone, vimentin alone, and both antibodies together. Prostate cancer patients showed an average of 13.29, 11.13, and 27.95 CTCs/mL isolated using EpCAM alone, vimentin alone, and both antibodies, respectively. For pancreatic cancer patients, the averages were 1.50, 3.44, and 10.82 CTCs/mL with EpCAM alone, vimentin alone, and both antibodies, respectively. Combining antibodies more than doubled CTC isolation compared to single antibodies. Interestingly, EpCAM antibodies were more effective for localized prostate cancer, while vimentin antibodies excelled in metastatic prostate cancer isolation. Moreover, vimentin antibodies outperformed EpCAM antibodies for all pancreatic cancer patients. These results highlight that using both epithelial and mesenchymal antibodies with the lateral magnetophoretic microseparator significantly enhances CTC isolation efficiency, and that antibody choice may vary depending on cancer type and stage.

Actuating compact wearable augmented reality devices by multifunctional artificial muscle.

An artificial muscle actuator resolves practical engineering problems in compact wearable devices, which are limited to conventional actuators such as electromagnetic actuators. Abstracting the fundamental advantages of an artificial muscle actuator provides a small-scale, high-power actuating system with a sensing capability for developing varifocal augmented reality glasses and naturally fit haptic gloves. Here, we design a shape memory alloy-based lightweight and high-power artificial muscle actuator, the so-called compliant amplified shape memory alloy actuator. Despite its light weight (0.22 g), the actuator has a high power density of 1.7 kW/kg, an actuation strain of 300% under 80 g of external payload. We show how the actuator enables image depth control and an immersive tactile response in the form of augmented reality glasses and two-way communication haptic gloves whose thin form factor and high power density can hardly be achieved by conventional actuators.

Association of serum prostate-specific antigen (PSA) level and circulating tumor cell-based PSA mRNA in prostate cancer.

BACKGROUND: Prostate-specific antigen (PSA) is used for diagnosing prostate cancer, but does not reflect the characteristics of prostate cancer cells to allow assessment of cancer progression. PSA mRNA and circulating tumor cells (CTCs) could be potential biomarkers. However, the relationship between serum PSA levels and PSA mRNA in CTCs is unclear, and this study aimed to investigate this relationship. METHODS: Healthy donors (HD, n = 9), and patients with local non-metastatic stage prostate cancer (n = 30), metastatic hormone-sensitive prostate cancer (mHSPC, n = 10), and metastatic castration-resistant prostate cancer (mCRPC, n = 75), were included. The expression of PSA mRNA in CTCs was measured by droplet digital PCR. Serum PSA (ng/mL) levels and PSA mRNA (copies/µL) in CTCs were then compared using Spearman correlation coefficients. RESULTS: PSA mRNA expression in CTCs was observed in 30% (9/30) of patients with localized cancer, 60.0% (6/10) among patients with mHSPC, 65.3% (49/75) among patients with mCRPC, and 0% among patients with HD, indicating that the detection rate of PSA mRNA increased with cancer stage. PSA mRNA expression in CTCs also increased from localized to metastatic stages. PSA mRNA levels rapidly increased in the mHSPC and mCRPC stages. Interestingly, PSA mRNA expression in CTCs was not correlated with serum PSA levels at the localized stage (R = 0.064, P = 0.512). However, there were significant correlations between serum PSA levels and PSA mRNA expression in mHSPC (R = 0.532, P = 0.041) and mCRPC (R = 0.566, P = 0.025). The number of CTCs isolated from mHSPC and mCRPC was not proportional to serum PSA and PSA mRNA levels. CONCLUSION: CTC PSA mRNA has the potential to be used as a biomarker to complement serum PSA protein analysis or replace serum PSA in metastatic stages of prostate cancer.

Impact of short warm ischemic time on longitudinal kidney function and survival rate after partial nephrectomy for renal cell carcinoma in patients with pre-existing chronic kidney disease stage III: A multi-institutional propensity score-matched study.

PURPOSE: It remains unclear whether a short warm ischemic time (WIT) improves long-term renal function after partial nephrectomy (PN) for patients with pre-existing chronic kidney disease (CKD). We evaluated renal function after PN according to WIT duration in patients with stage III CKD. MATERIALS AND METHODS: We identified 277 patients with stage III CKD who underwent PN during 2004-2017. Propensity score matching was used to created two matched groups of patients: Group A (WIT of <25 min) and Group B (WIT of ≥25 min). The outcomes of interest were longitudinal kidney function change, new-onset stage IV CKD (eGFR <30 mL/min/1.73 m2) and overall survival. RESULTS: The two matched groups contained 85 patients each. The median follow-up durations were 49 months in Group A and 42 months in Group B. The median pre-treatment eGFRs were 52.4 mL/min/1.73 m2 in Group A and 52.6 mL/min/1.73 m2 in Group B. There were no differences in kidney function between the two groups throughout the follow-up period (P > 0.05). The 5-year rates of new-onset stage IV CKD were not significantly different between Group A and Group B (8.2% vs. 7.1%), with no significant difference in the risk of developing stage IV CKD in Group A (vs. group B, hazard ratio: 0.527, 95% confidence interval: 0.183-1.521; P = 0.236). The 5-year overall survival rates were 90.3% for Group A and 96.2% for Group B (P = 0.549). CONCLUSIONS: A short WIT was not associated with better postoperative kidney function or survival after PN in patients with stage III CKD.

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 implications of genomic evaluations for prostate cancer risk stratification, screening, and treatment: a narrative review.

New classification systems based on molecular features have been introduced to improve precision medicine for prostate cancer (PCa). This review covers the increasing risk of PCa and the differences in response to targeted therapy that are related to specific gene variations. We believe that genomic evaluations will be useful for guiding PCa risk stratification, screening, and treatment. We searched the PubMed and MEDLINE databases for articles related to genomic testing for PCa that were published in 2020 or earlier. There is increasing evidence that germline mutations in DNA repair genes, such as BRCA1/2 or ATM, are closely related to the development and aggressiveness of PCa. Targeted prostate-specific antigen screening based on the presence of germline alterations in DNA repair genes is recommend to achieve an early diagnosis of PCa. In cases of localized PCa, even if it has a favorable risk classification, patients under active surveillance with these gene alterations are likely to develop aggressive PCa. Thus, active treatment may be preferable to active surveillance for these patients. In cases of metastatic castration-resistant PCa, BRCA1/2 and DNA mismatch repair genes may be useful biomarkers for predicting the response to androgen receptor-targeting agents, poly (ADP-ribose) polymerase inhibitors, platinum chemotherapy, prostate-specific membrane antigen-targeted therapy, immunotherapy, and radium-223. Genomic evaluations may allow for risk stratification of patients with PCa based on their molecular features, which may help guide precision medicine for treating PCa.

A Direct Comparison between the Lateral Magnetophoretic Microseparator and AdnaTest for Isolating Prostate Circulating Tumor Cells.

Circulating tumor cells (CTCs) are important biomarkers for the diagnosis, prognosis, and treatment of cancer. However, because of their extreme rarity, a more precise technique for isolating CTCs is required to gain deeper insight into the characteristics of cancer. This study compares the performance of a lateral magnetophoretic microseparator ("CTC-µChip"), as a representative microfluidic device, and AdnaTest ProstateCancer (Qiagen), as a commercially available specialized method, for isolating CTCs from the blood of patients with prostate cancer. The enumeration and genetic analysis results of CTCs isolated via the two methods were compared under identical conditions. In the CTC enumeration experiment, the number of CTCs isolated by the CTC-µChip averaged 17.67 CTCs/mL, compared to 1.56 CTCs/mL by the AdnaTest. The number of contaminating white blood cells (WBCs) and the CTC purity with the CTC-µChip averaged 772.22 WBCs/mL and 3.91%, respectively, whereas those with the AdnaTest averaged 67.34 WBCs/mL and 1.98%, respectively. Through genetic analysis, using a cancer-specific gene panel (AR (androgen receptor), AR-V7 (A\androgen receptor variant-7), PSMA (prostate specific membrane antigen), KRT19 (cytokeratin-19), CD45 (PTPRC, Protein tyrosine phosphatase, receptor type, C)) with reverse transcription droplet digital PCR, three genes (AR, AR-V7, and PSMA) were more highly expressed in cells isolated by the CTC-µChip, while KRT19 and CD45 were similarly detected using both methods. Consequently, this study showed that the CTC-µChip can be used to isolate CTCs more reliably than AdnaTest ProstateCancer, as a specialized method for gene analysis of prostate CTCs, as well as more sensitively obtain cancer-associated gene expressions.

Wnt Signaling Drives Prostate Cancer Bone Metastatic Tropism and Invasion.

Wnt signaling has been implicated as a driver of prostate cancer-related osteoblast differentiation, and previous studies have linked modifications in Wnt function with the induction of tumor metastasis. A unique aspect of prostate cancer bone metastases in mouse models is their relative predilection to the hindlimb (femur) compared to the forelimb (humerus). Comparative gene expression profiling was performed within the humerus and femur from non-tumor-bearing mice to evaluate differences in the microenvironments of these locations. This revealed the relative overexpression of the Wnt signaling inhibitors WIF1 and SOST in the humerus compared to the femur, with increased WNT5A expression in femur bone marrow, suggesting a coordinated upregulation of Wnt signals within the femur compared to the humerus. Conditioned medium (CM) from bone marrow stromal cells (HS-5 cells) was used to mimic the bone marrow microenvironment, which strongly promoted prostate cancer cell invasion (3.3-fold increase in PC3 cells, P < .05; 7-fold increase in LNCaP cells, P < .05). WNT5A shRNA knockdown within the CM-producing HS-5 cells significantly decreased PC3 (56%, P < .05) and LNCaP (60%, P < .05) cell invasion. Similarly, preincubation of CM with WIF1 significantly blocked LNCaP cell invasion (40%, P < .05). shRNA-mediated knockdown of the Wnt receptors FZD4 and FZD8 also strongly inhibited tumor cell invasion (60% inhibition shFZD4, P < .05; 63% shFZD8, P < .05). Furthermore, small molecule inhibition of JNK, which is an important component of the noncanonical Wnt signaling pathway, significantly inhibited CM-mediated tumor invasion. Overall, this study reveals a role for Wnt signaling as a driver of prostate cancer bone metastatic tropism and invasion.

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.

Factors affecting the response rate of frequency volume chart: A prospective nonrandomized controlled study.

AIMS: To evaluate if compliance with frequency volume charts can be improved if a physician explains its importance and to identify factors affecting compliance and accurate responses to frequency volume chart (FVC). METHODS: We identified patients ≥18 years of age with voiding dysfunction reported from July 2013 to February 2014. Patients were explained the importance of frequency volume charts by a doctor and then a nurse explained how to fill it (group A). Others were only explained how to fill it (group B). RESULTS: A total of 137 patients were enrolled. The response rate to frequency volume charts was higher in group A than in group B (94.3% vs 82.9%, P = .038). Patients ≥70 years of age, without a private health insurance, with high school education or higher, and without past medical history had a higher response rate in group A than in group B. In the multivariate binary logistic regression analysis, group A (odds ratio [OR], 4.87; 95% confidence interval [95% CI], 1.04-22.89; P = .045) and QoL (OR, 2.28; 95% CI, 1.16-4.46; P = .017) were factors associated with the response rate. In addition, group A (OR, 3.46; 95% CI, 1.03-11.70; P = .045) and being 60's years old (vs 50's years, OR, 7.01; 95% CI, 1.36-36.23; P = .020) were related to FVC complete response rate. CONCLUSIONS: Frequency volume chart compliance can be improved if physicians explain its importance for lower urinary tract symptoms diagnosis and management. The explanation and severe lower urinary tract symptoms are factors affecting compliance and the explanation and being 60's years old are related to accurate response.

Circulating Tumor Cell-Based Molecular Classifier for Predicting Resistance to Abiraterone and Enzalutamide in Metastatic Castration-Resistant Prostate Cancer.

While circulating tumor cell (CTC)-based detection of AR-V7 has been demonstrated to predict patient response to second-generation androgen receptor therapies, the rarity of AR-V7 expression in metastatic castrate-resistant prostate cancer (mCRPC) suggests that other drivers of resistance exist. We sought to use a multiplex gene expression platform to interrogate CTCs and identify potential markers of resistance to abiraterone and enzalutamide. 37 patients with mCRPC initiating treatment with enzalutamide (n = 16) or abiraterone (n = 21) were prospectively enrolled for CTC collection and gene expression analysis using a panel of 89 prostate cancer-related genes. Gene expression from CTCs was correlated with PSA response and radioclinical progression-free survival (PFS) using Kaplan-Meier and Cox regression analyses. Twenty patients (54%) had detectable CTCs. At a median follow-up of 11.3 months, increased expression of the following genes was significantly associated with shorter PSA PFS and radioclinical PFS: AR, AR-V7, PSA, PSCA, TSPAN8, NKX3.1, and WNT5B. Additionally, high SPINK1 expression was associated with increased PFS. A predictive model including all eight genes gave an area under the curve (AUC) of 0.84 for PSA PFS and 0.86 for radioclinical PFS. In comparison, the AR-V7 only model resulted in AUC values of 0.65 and 0.64.These data demonstrate that clinically relevant information regarding gene expression can be obtained from whole blood using a CTC-based approach. Multigene classifiers in this setting may allow for the development of noninvasive predictive biomarkers to guide clinical management.

Detection of CTC Clusters and a Dedifferentiated RNA-Expression Survival Signature in Prostate Cancer.

Rates of progression and treatment response in advanced prostate cancer are highly variable, necessitating non-invasive methods to assess the molecular characteristics of these tumors in real time. The unique potential of circulating tumor cells (CTCs) to serve as a clinically useful liquid biomarker is due to their ability to inform via both enumeration and RNA expression. A microfluidic graphene oxide-based device (GO Chip) is used to isolate CTCs and CTC clusters from the whole blood of 41 men with metastatic castration-resistant prostate cancer. Additionally, the expression of 96 genes of interest is determined by RT-qPCR. Multivariate analyses are conducted to determine the genes most closely associated with overall survival, PSA progression, and radioclinical progression. A preliminary signature, comprising high expression of stemness genes and low expression of epithelial and mesenchymal genes, potentially implicates an undifferentiated CTC phenotype as a marker of poor prognosis in this setting.

Surgical managements of pseudoepitheliomatous keratotic and micaceous balanitis: A case report.

INTRODUCTION: Pseudoepitheliomatous keratotic and micaceous balanitis (PKMB) is an extremely rare disease. Herein, we report a case of PKMB in a patient who underwent two surgical procedures, since the 5-FU cream was not available. PRESENTATION OF CASE: A 50 year-old Korean man undergoing circumcision in a local clinic presented with a tumor-like lesion on the glans penis. Peeling the mass was performed to remove the entire mass after an excisional biopsy. A pathologic finding of mass showed hyperkeratotic and papillomatous squamous epithelium without obvious cytologic atypia. Considering that the lesion recurred after 4 weeks, the patient underwent glansectomy with split-thickness skin graft (STSG). There had been no evidence of recurrence at the surgical site during the follow-up at 6 years postoperatively. DISCUSSION: If the 5-FU cream is not available, two surgical procedures can be performed for treatment and biopsy. Peeling the mass has the advantage of confirming the characteristics of the whole lesion, but it cannot confirm tumor invasion because it is unable to obtain the subepithelial layer. Glansectomy is able to accurately identify the tumor stage because it removes the tumor and total glans penis and has excellent outcome. CONCLUSION: PKMB is very rare and has a characteristic appearance, which is mica-like crusts and keratotic horny mass on the glans penis. Glansectomy with STSG is a good procedure when the 5-FU cream was not available.

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.

CXCL12γ Promotes Metastatic Castration-Resistant Prostate Cancer by Inducing Cancer Stem Cell and Neuroendocrine Phenotypes.

There is evidence that cancer stem-like cells (CSC) and neuroendocrine behavior play critical roles in the pathogenesis and clinical course of metastatic castration-resistant prostate cancer (m-CRPC). However, there is limited mechanistic understanding of how CSC and neuroendocrine phenotypes impact the development of m-CRPC. In this study, we explored the role of the intracellular chemokine CXCL12γ in CSC induction and neuroendocrine differentiation and its impact on m-CRPC. CXCL12γ expression was detected in small-cell carcinoma of metastatic tissues and circulating tumor cells from m-CRPC patients and in prostate cancer cells displaying an neuroendocrine phenotype. Mechanistic investigations demonstrated that overexpression of CXCL12γ induced CSC and neuroendocrine phenotypes in prostate cancer cells through CXCR4-mediated PKCα/NFκB signaling, which promoted prostate tumor outgrowth, metastasis, and chemoresistance in vivo Together, our results establish a significant function for CXCL12γ in m-CRPC development and suggest it as a candidate therapeutic target to control aggressive disease.Significance: Expression of CXCL12γ induces the expression of a cancer stem cell and neuroendocrine phenotypes, resulting in the development of aggressive m-CRPC. Cancer Res; 78(8); 2026-39. ©2018 AACR.

Multigene Profiling of CTCs in mCRPC Identifies a Clinically Relevant Prognostic Signature.

The trend toward precision-based therapeutic approaches dictated by molecular alterations offers substantial promise for men with metastatic castration-resistant prostate cancer (mCRPC). However, current approaches for molecular characterization are primarily tissue based, necessitating serial biopsies to understand changes over time and are limited by the challenges inherent to extracting genomic material from predominantly bone metastases. Therefore, a circulating tumor cell (CTC)-based assay was developed to determine gene expression across a panel of clinically relevant and potentially actionable prostate cancer-related genes. CTCs were isolated from the whole blood of mCRPC patients (n = 41) and multiplex qPCR was performed to evaluate expression of prostate cancer-related target genes (n = 78). A large fraction of patients (27/41, 66%) had detectable CTCs. Increased androgen receptor (AR) expression (70% of samples) and evidence of Wnt signaling (67% of samples) were observed. The TMPRSS2:ERG fusion was expressed in 41% of samples, and the aggressive prostate cancer-associated long noncoding RNA SChLAP1 was upregulated in 70%. WNT5a [HR 3.62, 95% confidence interval (CI), 1.63-8.05, P = 0.002], AURKA (HR 5.56, 95% CI, 1.79-17.20, P = 0.003), and BMP7 (HR 3.86, 95% CI, 1.60-9.32, P = 0.003) were independently predictive of overall survival (FDR < 10%) after adjusting for a panel of previously established prognostic variables in mCRPC (Halabi nomogram). A model including Halabi, WNT5a, and AURKA expression, termed the miCTC score, outperformed the Halabi nomogram alone (AUC = 0.89 vs. AUC = 0.70). Understanding the molecular landscape of CTCs has utility in predicting clinical outcomes in patients with aggressive prostate cancer and provides an additional tool in the arsenal of precision-based therapeutic approaches in oncology.Implications: Analysis of CTC gene expression reveals a clinically prognostic "liquid biopsy" signature in patients with metastatic castrate-resistance prostate cancer. Mol Cancer Res; 16(4); 643-54. ©2018 AACR.

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.

Selection Criteria for Active Surveillance of Patients with Prostate Cancer in Korea: A Multicenter Analysis of Pathology after Radical Prostatectomy.

PURPOSE: Korean patients with prostate cancer (PC) typically present with a more aggressive disease than patients in Western populations. Consequently, it is unclear if the current criteria for active surveillance (AS) can safely be applied to Korean patients. Therefore, this study was conducted to define appropriate selection criteria for AS for patients with PC in Korea. MATERIALS AND METHODS: We conducted a multicenter retrospective study of 2,126 patients with low risk PC who actually underwent radical prostatectomy. The primary outcome was an unfavorable disease, which was defined by non-organ confined disease or an upgrading of the Gleason score to ≥ 7 (4+3). Predictive variables of an unfavorable outcome were identified by multivariate analysis using randomly selected training samples (n=1,623, 76.3%). We compared our selected criteria to various Western criteria for the primary outcome and validated our criteria using the remaining validation sample (n=503, 23.7%). RESULTS: A non-organ confined disease rate of 14.9% was identified, with an increase in Gleason score ≥ 7 (4+3) of 8.7% and a final unfavorable disease status of 20.8%. The following criteria were selected: Gleason score ≤ 6, clinical stage T1-T2a, prostate-specific antigen (PSA) ≤ 10 ng/mL, PSA density < 0.15 ng/mL/mL, number of positive cores ≤ 2, and maximum cancer involvement in any one core ≤ 20%. These criteria provided the lowest unfavorable disease rate (11.7%) when compared to Western criteria (13.3%-20.7%), and their validity was confirmed using the validation sample (5.9%). CONCLUSION: We developed AS criteria which are appropriate for Korean patients with PC. Prospective studies using these criteria are now warranted.