Evaluation of prostate cancer detection using micro-ultrasound versus MRI through co-registration to whole-mount pathology.

Micro-ultrasound has recently been introduced as a low-cost alternative to multi-parametric MRI for imaging prostate cancer. Early clinical studies have demonstrated promising results; however, robust validation via comparison with whole-mount pathology has yet to be achieved. Due to micro-ultrasound probe design and tissue deformation during scanning, it is difficult to accurately correlate micro-ultrasound imaging planes with ground truth whole-mount pathology slides.

Role of Forkhead Box P3 in IFNγ-Mediated PD-L1 Expression and Bladder Cancer Epithelial-to-Mesenchymal Transition.

Unlabelled: Antagonism of the PD-1/PD-L1 axis is a critical therapeutic strategy for patients with advanced bladder cancer. IFNγ functions as a key regulator of PD-L1 in both immune as well as cancer cells. Forkhead box P3 (FOXP3) is a transcription factor synonymous in T regulatory cell function but with increasingly described functions in cancer cells.

UCHL1 is a potential molecular indicator and therapeutic target for neuroendocrine carcinomas.

Neuroendocrine carcinomas, such as neuroendocrine prostate cancer and small-cell lung cancer, commonly have a poor prognosis and limited therapeutic options. We report that ubiquitin carboxy-terminal hydrolase L1 (UCHL1), a deubiquitinating enzyme, is elevated in tissues and plasma from patients with neuroendocrine carcinomas. Loss of UCHL1 decreases tumor growth and inhibits metastasis of these malignancies.

Tumor heterogeneity in VHL drives metastasis in clear cell renal cell carcinoma.

Loss of function of the von Hippel-Lindau (VHL) tumor suppressor gene is a hallmark of clear cell renal cell carcinoma (ccRCC). The importance of heterogeneity in the loss of this tumor suppressor has been under reported. To study the impact of intratumoral VHL heterogeneity observed in human ccRCC, we engineered VHL gene deletion in four RCC models, including a new primary tumor cell line derived from an aggressive metastatic case.

Donor-Derived Urothelial Carcinoma in Renal Transplant Recipients.

Cancer is a significant cause of morbidity and mortality in recipients of renal transplantation. The vast majority develop from recipient origins, whereas donor-derived malignancies are exceedingly rare. We report 2 cases of poorly differentiated donor-derived urothelial carcinoma (UC) in renal transplantation recipients.

A genetically defined disease model reveals that urothelial cells can initiate divergent bladder cancer phenotypes.

Small cell carcinoma of the bladder (SCCB) is a rare and lethal phenotype of bladder cancer. The pathogenesis and molecular features are unknown. Here, we established a genetically engineered SCCB model and a cohort of patient SCCB and urothelial carcinoma samples to characterize molecular similarities and differences between bladder cancer phenotypes.

Establishment of xenografts of urological cancers on chicken chorioallantoic membrane (CAM) to study metastasis.

Cancer of the urological system commonly occurs in the kidney, bladder, and prostate gland. The clear cell subtype of renal cell carcinoma (ccRCC) constitutes the great majority of kidney cancer. Metastatic ccRCC portends a very poor outcome with no effective treatment available.

Development and Validation of an Automated Method to Identify Patients Undergoing Radical Cystectomy for Bladder Cancer Using Natural Language Processing.

Introduction: Measurement for quality improvement relies on accurate case identification and characterization. With electronic health records now widely deployed, natural language processing, the use of software to transform text into structured data, may enrich quality measurement. Accordingly we evaluated the application of natural language processing to radical cystectomy procedures for patients with bladder cancer.

Sequencing of cancer cell subpopulations identifies micrometastases in a bladder cancer patient.

Purpose: Pathologic staging of bladder cancer patients remains a challenge. Standard-of-care histology exhibits limited sensitivity in detection of micrometastases, which can increase risk of cancer progression and delay potential adjuvant therapies. Here, we sought to develop a proof of concept novel molecular approach to improve detection of cancer micrometastasis.

Biased Expression of the FOXP3Δ3 Isoform in Aggressive Bladder Cancer Mediates Differentiation and Cisplatin Chemotherapy Resistance.

Purpose: The transcriptional regulation mediating cancer cell differentiation into distinct molecular subtypes and modulating sensitivity to existing treatments is an enticing therapeutic target. Our objective was to characterize the ability of the forkhead/winged transcription factor FOXP3 to modulate the differentiation of bladder cancer.

Experimental Design: Expression of FOXP3 was analyzed by immunohistochemistry in a tumor microarray of 587 samples and overall survival in a subset of 187 patients following radical cystectomy.

How nerve-sparing technique has been applied to radiotherapy?

The introduction of nerve-sparing technique is one of the most significant advances in the surgical treatment of prostate cancer and heralded a shift from a curing cancer at all-cost model to a curing cancer and preserving quality of life model. In a recent article published in in May, Lee . reviewed the concept of vessel-sparing and functional anatomy-based radiotherapy as well as outcomes with respect to erectile dysfunction, bringing to light a conceptual shift in the management of localized prostate cancer with radiotherapy, which parallels the shift in the surgical management of prostate cancer with the introduction of nerve-sparing technique.

Gleason 6 Prostate Cancer: Translating Biology into Population Health.

Purpose: Gleason 6 (3+3) is the most commonly diagnosed prostate cancer among men with prostate specific antigen screening, the most histologically well differentiated and is associated with the most favorable prognosis. Despite its prevalence, considerable debate exists regarding the genetic features, clinical significance, natural history, metastatic potential and optimal management.

Materials And Methods: Members of the Young Urologic Oncologists in the Society of Urologic Oncology cooperated in a comprehensive search of the peer reviewed English medical literature on Gleason 6 prostate cancer, specifically focusing on the history of the Gleason scoring system, histological features, clinical characteristics, practice patterns and outcomes.

Synergy of Histone-Deacetylase Inhibitor AR-42 with Cisplatin in Bladder Cancer.

Purpose: Cisplatin based chemotherapy regimens form the basis of systemic bladder cancer treatment, although they show limited response rates and efficacy. Recent molecular analysis of bladder cancer revealed a high incidence of mutations in chromatin regulatory genes, suggesting a therapeutic avenue for histone deacetylase inhibitors. We investigated the ability of the novel histone deacetylase inhibitor AR-42 to synergize with cisplatin in preclinical models of bladder cancer.

Loss of MyD88 leads to more aggressive TRAMP prostate cancer and influences tumor infiltrating lymphocytes.

Background: The influence of pattern recognition receptor (PRR) signaling in the prostate tumor microenvironment remains unclear. Although there may be a role for PRR agonists as adjuvants to therapy, prior evidence suggests tumor promoting as well as tumor inhibiting mechanisms. The purpose of this study is to examine the role of the key Toll-like receptor (TLR) signaling adaptor protein myeloid differentiation primary response gene 88 (MyD88) in prostate cancer development.

RARP in high-risk prostate cancer: use of multi-parametric MRI and nerve sparing techniques.

To examine the outcomes of patients with high-risk prostate cancer (PCa) treated by robot-assisted radical prostatectomy (RARP) and evaluate the value of multi-parametric magnetic resonance imaging (MRI) in estimating tumor stage, extracapsular extension, and grade, and the application of nerve sparing (NS) techniques. Patient demographics, preoperative imaging, surgical parameters, pathological features, functional and recurrence outcomes were collected retrospectively in patients with high-risk PCa who underwent RARP between December 2009 and October 2013. Pathological whole mount slides to assess NS were compared with potency, recovery of continence, and surgical margins (SM).

Role of Rip2 in development of tumor-infiltrating MDSCs and bladder cancer metastasis.

Tumor invasion and metastases represent a complex series of molecular events that portends a poor prognosis. The contribution of inflammatory pathways mediating this process is not well understood. Nod-like receptors (NLRs) of innate immunity function as intracellular sensors of pathogen motifs and danger molecules.

Karnofsky performance status predicts overall survival, cancer-specific survival, and progression-free survival following radical cystectomy for urothelial carcinoma.

Objective: Radical cystectomy (RC) can provide a survival advantage in patients with urothelial carcinoma of the bladder, but not without significant morbidity rates. Whether the ability of preoperative comorbidity or performance status metrics can stratify patients to overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) following RC is unclear. We analyze our RC experience from 2005 to 2010 to assess the prognostic power of American Society of Anesthesiologists (ASA) score, Charlson Comorbidity Index (CCI), and Karnofsky Performance Status (KPS) index as they relate to OS, CSS, and PFS.

Primary carcinoid tumor of urinary bladder discovered on pelvic magnetic resonance imaging.

Pure primary carcinoid tumor of the urinary bladder is an exceedingly rare lesion with less than twenty cases reported in the English language literature. These tumors are typically small and rarely invade past the lamina propria. Amenable to transurethral resection alone, they are associated with a favorable prognosis.

Ultrasound-based combination therapy: potential in urologic cancer.

Immune-sensitive urologic malignancies include prostate, kidney and bladder cancers. To date, most immunotherapeutic treatments have been applied to advanced metastatic disease. Limited efficacy in this setting is likely due to an excessive disease burden, which overwhelms the capacity of the immune system.

Immunological therapy in urological malignancy: novel combination strategies.

At present, immunotherapy in urological malignancy is experiencing a renaissance, particularly with the emergence of a host of innovative cancer vaccines. Herein, we will review promising immunotherapeutic approaches and evaluate the data supporting their inclusion in novel combination strategies.

Toll-like receptor 3-mediated suppression of TRAMP prostate cancer shows the critical role of type I interferons in tumor immune surveillance.

Inflammation has increasingly been recognized as a critical component influencing tumor growth. Recent reports have revealed conflicting evidence for the role of Toll-like receptors (TLR) in modulating tumorigenesis. In our study, we implicate TLR3 in mediating immune surveillance with increased growth of implanted transgenic adenocarcinoma of the mouse prostate (TRAMP) tumors in TLR3(-/-) compared with TLR3(+/+) mice.

Is repeat biopsy for isolated high-grade prostatic intraepithelial neoplasia necessary?

Numerous studies have cited the positive predictive value of isolated highgrade prostatic intraepithelial neoplasia (HGPIN) to the detection of cancer. Epidemiological, morphological, and molecular data support the potential for malignant transformation of HGPIN, yet no current method can discriminate which lesions will progress to clinically significant prostate cancer versus more latent lesions. Recent analyses of multiple retrospective studies have found similar rates of cancer detection following either diagnosis of isolated HGPIN or an initial negative biopsy.

Transverse vaginal septum with congenital vesical-vaginal communication and cyclical hematuria.

Cyclical hematuria is an unusual presentation of a müllerian fusion anomaly. We report a patient with transverse vaginal septum and menstruation by way of the lower urinary tract because of a vesical-vaginal communication. A defect of vertical fusion, transverse vaginal septum results from failure of canalization of the vaginal plate.