Robotic transperineal prostate biopsy: pilot clinical study.

OBJECTIVE: To develope a robot (BioXbot) that performs mapping transperineal prostate biopsy (PB) with two perineal skin punctures under ultrasound guidance. Our pilot study's clinical endpoints were complications and its technical endpoints were the duration for each phase. METHODS: This institution review board-approved prospective clinical trial included patients with indications for PB. Two urologists performed these PBs. In the lithotomy position and under general anesthesia, the transrectal biplane ultrasound probe acquired transverse images of the prostate gland. The urologist defined its boundaries and planned the biopsy. It guided the PB in 3 axes, passing through a single perineal skin puncture for each prostate side. After each biopsy, it automatically moved to the next position. The steps were repeated on the contralateral side. RESULTS: Our 20 patients had a mean prostate-specific antigen of 8.4 ± 4.9 ng/mL. Two patients had 2 previous biopsies, whereas the rest had one. The mean number of biopsies taken was 28.5 ± 6.2 in a mean total procedure time of 32.5 ± 3.2 minutes. We detected 3 patients with prostate cancer with Gleason score 3 + 3. Two patients required brief bladder catheterization after their biopsy. Their prostate volumes were >50 mL and the number of biopsies taken was >30 cores. There was no mechanical failure, sepsis, bleeding per-rectal, or perineal hematoma. CONCLUSION: This pilot study demonstrated BioXbot's safety and feasibility as a biopsy platform. It can potentially be used for image-guided PB and focal therapy.

Inhibition of angiogenic and non-angiogenic targets by sorafenib in renal cell carcinoma (RCC) in a RCC xenograft model.

BACKGROUND: It is widely recognised that sorafenib inhibits a range of molecular targets in renal cell carcinoma (RCC). In this study, we aim to use patient-derived RCC xenografts to delineate the angiogenic and non-angiogenic molecular targets of sorafenib therapy for advanced RCC (aRCC). METHODS: We successfully generated three patient RCC-derived xenografts in severe combined immunodeficient mice, consisting of three different RCC histological subtypes: conventional clear cell, poorly differentiated clear cell RCC with sarcomatoid changes, and papillary RCC. This study also used clear cell RCC cells (786-0/EV) harbouring mutant VHL to investigate the clonogenic survival of cells transfected with survivin sense and antisense oligonucleotides. RESULTS: All three xenografts retain their original histological characteristics. We reported that sorafenib inhibited all three RCC xenograft lines regardless of histological subtypes in a dose-dependant manner. Sorafenib-induced growth suppression was associated with not only inhibition of angiogenic targets p-PDGFR-ß, p-VEGFR-2, and their downstream signalling pathways p-Akt and p-ERK, cell cycle, and anti-apoptotic proteins that include cyclin D1, cyclin B1, and survivin but also upregulation of proapoptotic Bim. Survivin knockdown by survivin-specific antisense-oligonucleotides inhibited colony formation and induced cell death in clear cell RCC cells. CONCLUSION: This study has shed light on the molecular mechanisms of sorafenib in RCC. Inhibition of non-angiogenic molecules by sorafenib could contribute in part to its anti-tumour activities observed in vivo, in addition to its anti-angiogenic effects.

Robotic ultrasound-guided prostate intervention device: system description and results from phantom studies.

BACKGROUND: We introduce the first robotic ultrasound-guided prostate intervention device and evaluate its safety, accuracy and repeatability. METHODS: The robotic positioning system (RPS) determines a target's x, y and z axes. It is situated with a biplane ultrasound probe on a mobile horizontal platform. The integrated software acquires ultrasound images for three-dimensional (3D) modelling, coordinates target planning and directs the RPS. RESULTS: The egg phantom evaluates the software's safety and workflow protocol. Two random targets are planned in each quadrant and biopsy needles are inserted. All were within three separate eggs. Metal wire tips are targeted and their distances from the biopsy needle tips are measured. With 20 wires, < 1 mm accuracy is obtained. Repeatability is demonstrated when previous positions are returned to with similar accuracy. CONCLUSION: Our device demonstrates safety in a defined boundary with a repeatable accuracy of < 1 mm. It can be used for accurate prostate biopsy and treatment delivery.

The VHL tumor suppressor inhibits expression of the IGF1R and its loss induces IGF1R upregulation in human clear cell renal carcinoma.

Clear cell renal cell cancer (CC-RCC) is a highly chemoresistant tumor characterized by frequent inactivation of the von Hippel-Lindau (VHL) gene. The prognosis is reportedly worse in patients whose tumors express immunoreactive type I insulin-like growth factor receptor (IGF1R), a key mediator of tumor cell survival. We aimed to investigate how IGF1R expression is regulated, and found that IGF1R protein levels were unaffected by hypoxia, but were higher in CC-RCC cells harboring mutant inactive VHL than in isogenic cells expressing wild-type (WT) VHL. IGF1R mRNA and promoter activities were significantly lower in CC-RCC cells expressing WT VHL, consistent with a transcriptional effect. In Sp1-null Drosophila Schneider cells, IGF1R promoter activity was dependent on exogenous Sp1, and was suppressed by full-length VHL protein (pVHL) but only partially by truncated VHL lacking the Sp1-binding motif. pVHL also reduced the stability of IGF1R mRNA via sequestration of HuR protein. Finally, IGF1R mRNA levels were significantly higher in CC-RCC biopsies than benign kidney, confirming the clinical relevance of these findings. Thus, we have identified a new hypoxia-independent role for VHL in suppressing IGF1R transcription and mRNA stability. VHL inactivation leads to IGF1R upregulation, contributing to renal tumorigenesis and potentially also to chemoresistance.

Endorectal magnetic resonance imaging and spectroscopy for the detection of tumor foci in men with prior negative transrectal ultrasound prostate biopsy.

PURPOSE: We determined the ability of combined endorectal magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI) to detect prostate cancer foci prospectively in men with prior negative transrectal ultrasound (TRUS) prostate biopsy. MATERIALS AND METHODS: Endorectal MRI with spectroscopy was performed in 24 consecutive patients with 1 or more prior negative TRUS prostatic biopsies for persistently increased prostate specific antigen and/or abnormal digital rectal examination. All studies were interpreted by a dedicated radiologist who reported areas of interest in the peripheral zone as normal, equivocal or suspicious on MRI and MRSI separately. Equivocal and suspicious areas were then correlated with a 3-dimensional prostate model. All patients underwent a standard TRUS 10-core peripheral zone biopsy with up to 4 additional biopsies targeted at the equivocal or suspected sites. RESULTS: Prostate cancer was detected in 7 of 24 subjects (29.2%). Considering the equivocal category as test negative the sensitivity, specificity, positive and negative predictive values, and the accuracy of MRI, MRSI and combined MRI/MRSI for the detection of prostate cancer were 57.1%, 57.1% and 100.0%, 88.2%, 82.4% and 70.6%, 66.7%, 57.1% and 58.3%, 83.3%, 82.1% and 100%, and 79.2%, 75.0% and 79.2%, respectively. The site of positive biopsy correlated correctly in 50% and 28.6% of MRI and MRSI labeled suspicious cores, respectively. CONCLUSIONS: MRI and MRSI have the potential to identify cancer foci and direct TRUS in patients with a previous negative TRUS biopsy. Further, larger studies are required to quantify the amount of benefit.