John Shyi Peng Yuen

Effects of bladder volume on transabdominal ultrasound measurements of intravesical prostatic protrusion and volume

Background: A filled bladder acts as an acoustic window for transabdominal ultrasound measurements of intravesical prostatic protrusion and volume. The aim of this study is to evaluate the effects of bladder volume on transabdominal ultrasound measurements of these parameters.

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

We introduce the first robotic ultrasound‐guided prostate intervention device and evaluate its safety, accuracy and repeatability.

Robotic transperineal prostate biopsy: pilot clinical study.

OBJECTIVEnTo develope a robot (BioXbot) that performs mapping transperineal prostate biopsy (PB) with two perineal skin punctures under ultrasound guidance. Our pilot studys clinical endpoints were complications and its technical endpoints were the duration for each phase.nnnMETHODSnThis 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.nnnRESULTSnOur 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.nnnCONCLUSIONnThis pilot study demonstrated BioXbots safety and feasibility as a biopsy platform. It can potentially be used for image-guided PB and focal therapy.

Phased-array Magnetic Resonance Imaging of the Prostate with Correlation to Radical Prostatectomy Specimens: Local Experience

PURPOSEnTo evaluate local experience of phased-array magnetic resonance imaging (MRI) in the staging of locally advanced prostate carcinoma with comparison to clinical staging.nnnMETHODSnThe study population was 21 patients who underwent preoperative MRI with pelvic phased-array coils followed by radical prostatectomy. The MRI findings were correlated with completely embedded serially sliced and whole-mounted sections of the prostate gland and clinical staging.nnnRESULTSnOverall accuracy of 57.1% was obtained, with specificity of 90.0% and sensitivity of 27.3%. All but one case of locally advanced disease missed by MRI was microscopic. Clinical staging in these cases also achieved accuracy of 57.1%, specificity of 90.0% and sensitivity of 27.3%.nnnCONCLUSIONSnMRI with a phased-array coil has high specificity but low sensitivity for detection of extraprostatic disease. Phased-array MRI does not image microscopic tumour extension. It did not perform better than clinical staging and is not recommended for routine staging.

Improved Detection Rate of Prostate Cancer Using the 10-Core Biopsy Strategy in Singapore

OBJECTIVESnTo evaluate if changing the biopsy regime to 10 cores might improve the positive predictive value (PPV) of elevated prostate-specific antigen [PSA, elevated range, 4 to 20 ng per ml, normal range, < 4 ng per ml] for the diagnosis of prostate carcinoma.nnnMETHODSnFrom February 2000 to April 2001, 191 patients, mean age 64 years [range, 38 to 85 yr], underwent transrectal ultrasound [TRUS] for either elevated PSA [elevated range, 4 to 20 ng per ml] and/or abnormal digital rectal examination [DRE]. A 10-core TRUS-guided biopsy of the prostate was performed. This included the standard sextant biopsy and two additional cores for each far lateral zone.nnnRESULTSnUsing this technique, 47 out of 191 patients [24.6%] had prostate cancer. The PPV for PSA levels of 4.1 to 10.0 ng per ml and 10.1 to 20.0 ng per ml were 19.3% and 35.4%, respectively. The lateral cores contributed 21.3% of the cancer cases, which would have been missed if only sextant biopsies were performed.nnnCONCLUSIONSnWith the 10-core biopsy method, the PPV for prostate cancer for patients with a PSA in the range of 4 to 20 ng per ml was in the range of 25%. This is significantly different from previous reports. The reason for this may be due to the adoption of a better, more uniform and systematic biopsy strategy for patients with elevated PSA, or it may be a true reflection of the current population incidence. Hence, this biopsy strategy is highly recommended.

Clinical, biochemical and pathological features of initial and repeat transrectal ultrasonography prostate biopsy positive patients

Background: Using sextant biopsy, 16–41% of prostate cancers were diagnosed on repeat biopsy. The objective of the present study was to compare the differences in the clinical, biochemical and pathological features between patients with positive results on initial and repeat biopsies, with an aim to identify factors that can be used to improve the detection rate of transrectal ultrasound (TRUS) biopsy of the prostate.

Combination of the ERK inhibitor AZD6244 and low-dose sorafenib in a xenograft model of human renal cell carcinoma

Sorafenib, a multikinase inhibitor, is currently used as monotherapy for advanced renal cell carcinoma (RCC). However, adverse effects associated with its use have been experienced by some patients. In this study, we examined the antitumor and antiangiogenic activities of low-dose sorafenib in combination with the MEK inhibitor AZD6244 (sorafenib/AZD6244) in a preclinical model of RCC. Primary RCC 08-0910 and RCCxa0786-0 cells as well as patient-derived RCC models were used to study the antitumor and antiangiogenic activities of sorafenib/AZD6244. Changes of biomarkers relevant to angiogenesis and cell cycle were determined by western immunoblotting. Microvessel density, apoptosis and cell proliferation were analyzed by immunohistochemistry. Treatment of RCC 786-0 cells with sorafenib/AZD6244 resulted in G1 cell cycle arrest and blockade of serum-induced cell migration. Sorafenib/AZD6244 induced apoptosis in primary RCC 08-0910 cells at low concentrations. Inxa0vivo addition of AZD6244 to sorafenib significantly augmented the antitumor activity of sorafenib and allowed dose reduction of sorafenib without compromising its antitumor activity. Sorafenib/AZD6244 potently inhibited angiogenesis and phosphorylation of VEGFR-2, PDGFR-β and ERK, p90RSK, p70S6K, cdk-2 and retinoblastoma. Sorafenib/AZD6244 also caused upregulation of p27, Bad and Bim but downregulation of survivin and cyclin B1. These resulted in a reduction in cellular proliferation and the induction of tumor cell apoptosis. Our findings showed that AZD6244 and sorafenib complement each other to inhibit tumor growth. This study provides sound evidence for the clinical investigation of low-dose sorafenib in combination with AZD6244 in patients with advanced RCC.

Action of YM155 on clear cell renal cell carcinoma does not depend on survivin expression levels

The dioxonapthoimidazolium YM155 is a survivin suppressant which has been investigated as an anticancer agent in clinical trials. Here, we investigated its growth inhibitory properties on a panel of immortalized and patient derived renal cell carcinoma (RCC) cell lines which were either deficient in the tumour suppressor von Hippel-Lindau (VHL) protein or possessed a functional copy. Neither the VHL status nor the survivin expression levels of these cell lines influenced their susceptibility to growth inhibition by YM155. Of the various RCC lines, the papillary subtype was more resistant to YM155, suggesting that the therapeutic efficacy of YM155 may be restricted to clear cell subtypes. YM155 was equally potent in cells (RCC786.0) in which survivin expression had been stably silenced or overexpressed, implicating a limited reliance on survivin in the mode of action of YM155. A follow-up in-vitro high throughput RNA microarray identified possible targets of YM155 apart from survivin. Selected genes (ID1, FOXO1, CYLD) that were differentially expressed in YM155-sensitive RCC cells and relevant to RCC pathology were validated with real-time PCR and western immunoblotting analyses. Thus, there is corroboratory evidence that the growth inhibitory activity of YM155 in RCC cell lines is not exclusively mediated by its suppression of survivin. In view of the growing importance of combination therapy in oncology, we showed that a combination of YM155 and sorafenib at ½ x IC50 concentrations was synergistic on RCC786.0 cells. However, when tested intraperitoneally on a murine xenograft model derived from a nephrectomised patient with clear cell RCC, a combination of suboptimal doses of both drugs failed to arrest tumour progression. The absence of synergy in vivo highlighted the need to further optimize the dosing schedules of YM155 and sorafenib, as well as their routes of administration. It also implied that the expression of other oncogenic proteins which YM155 may target is either low or absent in this clear cell RCC.

Control and safety aspects of medical robots for treatment of diseases of the prostate

Abstract There has been much advancement in the field of minimally invasive surgery in recent years. Medical robots play an important role in these improvements. Surgeons are fast accepting the aid of robots in laparoscopic, thorascopic, endoluminal and arthroscopic interventions, to name just a few. This paper reviews the state-of-the-art of medical robots that have been and are being developed for the purpose of treating diseases of the prostate. The main objective of these robots is to manoeuvre accurately a surgical tool via the transrectal or transurethral route to perform a surgical procedure on the prostate based on ultrasound guidance. The system approaches and control methodologies of these robots are highlighted. However, the main emphasis is on the safety aspects, both hardware and software, which are discussed in detail. Many of these safety features have been incorporated in the mentioned medical robots to enhance their reliability and safety.

Outcomes of combination MRI-targeted and transperineal template biopsy in restaging low-risk prostate cancer for active surveillance

Objective Active surveillance (AS) offers a strategy to reduce overtreatment and now is a widely accepted treatment option for low-risk prostate cancer. An ideal tool for risk-stratification would detect aggressive cancers and exclude such men from taking up AS in the first place. We evaluate if a combination of transperineal template biopsy with magnetic resonance imaging (MRI)-targeted biopsy identifies significant prostate cancer amongst men initially diagnosed with low-risk prostate cancer. Methods This prospective, single-blinded study included men with low-risk prostate cancer (DAmicos Criteria) diagnosed on conventional transrectal ultrasound-guided biopsy. Patients first underwent multiparametric MRI of the prostate ≥6 weeks after initial biopsy. Each suspicious lesion is mapped and assigned a Prostate Imaging Reporting and Data System (PIRADS) score. Template biopsy is first performed with the surgeon blinded to MRI findings followed by MRI-targeted biopsy using a robotic transperineal biopsy platform. Results The age of the 19 men included is 65.4 ± 4.9 years (mean ± SD). Prostate specific antigen (PSA) at diagnosis and at the time of transperineal biopsy were comparable (7.3 ± 1.7 ng/mL and 7.0 ± 1.8 ng/mL, p = 0.67), so were prostate volumes (34.2 ± 8.9 mL and 32.1 ± 13.4 mL, p = 0.28). MRI-targeted biopsy had a higher percentage of cancer detection per core compared to template biopsy (11.7% vs. 6.5%, p = 0.02), this was more than 3 times superior for Gleason 7 disease (5.9% vs. 1.6%, p < 0.01). Four of 18 (22.2%) patients with MRI lesions had significant disease with MRI-targeted biopsy alone. Three of 19 patients (15.8%) had significant disease with template biopsy alone. In combination, both techniques upclassified five patients (26.3%), all of whom underwent radical prostatectomy. Whole mount histology confirmed tumour location and grade. All six patients with PIRADS 5 lesions had cancer detected (66.6% significant disease). Conclusion A combination of MRI-targeted and template biopsy may optimally risk-classify “low-risk” patients diagnosed on initial conventional transrectal ultrasonography (TRUS) prostate biopsy.