Introduction:Nonmuscle invasive bladder cancer (NMIBC) remains a very challenging disease to treat with high rates of recurrence and progression associated with current therapies. Recent technological and biological advances have led to the development of novel agents in NMIBC therapy.Methods:We reviewed existing literature as well as currently active and recently completed clinical trials in NMIBC by querying PubMed.gov and clinicaltrials.gov.Results:A wide variety of new therapies in NMIBC treatment are currently being developed, utilizing recent developments in the understanding of immune therapies and cancer biology.Conclusion:The ongoing efforts to develop new therapeutic approaches for NMIBC look very promising and are continuing to evolve.
INTRODUCTION AND OBJECTIVES: Sepsis following transrectal ultrasound-guided (TRUS) biopsy is rising with numerous strategies aimed at curbing its incidence. Transperineal prostate biopsy has negligible rates of sepsis but has traditionally been reserved for saturation sampling, required general anesthesia, and use of a brachytherapy grid/stepper. Additionally, the adequacy of modified 12-core transperineal template mapping biopsy (TMB) is debated. Herein, we describe our initial experience with completely in-office free-hand transperineal prostate biopsy (TPBx) performed under local anesthesia.METHODS: A retrospective review was performed of patients who underwent TPBx at 2 institutions. TPBx was performed in lithotomy under TRUS guidance using a BK8848 biplanar probe after oral cephalosporin prophylaxis. Local anesthesia was administered via transperineal puncture and bolus delivery of anesthetic at the pelvic floor and through the endopelvic fascia anterior to the prostatic apex, bilaterally. The PrecisionPointTM device was used to access the left and right prostatic lobes to complete a modified barzell 12-core TMB. Patient characteristics and pathologic outcomes were collected and analyzed.RESULTS: A total of 87 biopsies were performed with data available for 30 biopsies performed on protocol. Patient characteristics and pathologic data are summarized in Table 1. Mean age and PSA of the cohort were 63.4 years and 6.9ng/ml. Six men had a prior prostate cancer diagnosis and underwent biopsy on surveillance. The overall cancer detection rate (CDR) was 57% and clinically significant CDR (Gleason !7) was 33%. There were no complications noted within 30 days of biopsy.CONCLUSIONS: Transperineal freehand prostate biopsy is effective for detection of prostate cancer. It is safe and well tolerated under local anesthesia, and can be performed in an office setting. Larger studies are required to validate this early experience.
in normal cells. We hypothesize that EVs derived from bladder cancer (BC) cells, by causing ER stress, impose a selection force in normal recipient cells that lead to a higher malignant transformation frequency.METHODS: EVs from TCC-SUP, a BC line, and SV-HUC cells, a non-malignant immortalized urothelial line, were collected by serial centrifugation, counted by nanoparticle tracking analysis, and examined by mass spectrometry. SV-HUC cells were chronically treated with TCC-SUP EVs and were determined by an in vitro colony formation assay and an in vivo xenograft mouse model. Some cancer cell properties: loss of contact inhibition, genome instability, and invasion were investigated. EVs provoked ER stress responses were assayed by Western blot.RESULTS: BC cells secreted a higher number of EVs than normal urothelial cells. These BCEVs carried distinct proteins; some were oncogenic and could induce normal recipient cells' pro-apoptotic ER stress response. Prolonged activation of ER stress led cells to switch to a pro-survival branch of ER stress response, and eventually, those cells were transformed and gained several cancerous properties. More importantly, inhibition of ER stress response by docosahexaenoic acid reduced BCEV-induced tumorigenesis.CONCLUSIONS: Our data provide a novel mechanism whereby prolonged ER stress induced by persistent exposure to tumorderived EVs drives the malignant transformation of clinically indolent recipient cells. This study provides insight into bladder cancer's multifocal and recurrent nature and suggests EVs as potential markers of disease recurrence and progression.
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