[Show abstract][Hide abstract] ABSTRACT: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell cancer (RCC), followed by papillary RCC (pRCC). It is important to distinguish these two subtypes because of prognostic differences and possible changes in management, especially in cases undergoing active surveillance. The purpose of our study is to evaluate the use of voxel-based whole-lesion (WL) enhancement parameters on contrast enhanced computed tomography (CECT) to distinguish ccRCC from pRCC.
In this institutional review board-approved study, we retrospectively queried the surgical database for post nephrectomy patients who had pathology proven ccRCC or pRCC and who had preoperative multiphase CECT of the abdomen between June 2009 and June 2011. A total of 61 patients (46 with ccRCC and 15 with pRCC) who underwent robotic assisted partial nephrectomy for clinically localized disease were included in the study. Multiphase CT acquisitions were transferred to a dedicated three-dimensional workstation, and WL regions of interest were manually segmented. Voxel-based contrast enhancement values were collected from the lesion segmentation and displayed as a histogram. Mean and median enhancement and histogram distribution parameters skewness, kurtosis, standard deviation, and interquartile range were calculated for each lesion. Comparison between ccRCC and pRCC was made using each imaging parameter. For mean and median enhancement, which had a normal distribution, independent t-test was used. For histogram distribution parameters, which were not normally distributed, Wilcoxon rank sum test was used.
ccRCC had significantly higher mean and median whole WL enhancement (p < 0.01) compared to pRCC on arterial, nephrographic, and excretory phases. ccRCC had significantly higher interquartile range and standard deviation (p < 0.01) and significantly lower skewness (p < 0.01) compared to pRCC on arterial and nephrographic phases. ccRCC had significantly lower kurtosis compared to pRCC on only the arterial phase.
Our study suggests that voxel-based WL enhancement parameters can be used as a quantitative tool to differentiate ccRCC from pRCC. Differentiating between the two main types of RCC would provide the patient and the treating physicians more information to formulate the initial approach to managing the patient's renal cancer.
[Show abstract][Hide abstract] ABSTRACT: There are distinct quantifiable features characterizing renal cell carcinomas on contrast-enhanced CT examinations, such as peak tumor enhancement, tumor heterogeneity, and percent contrast washout. While qualitative visual impressions often suffice for diagnosis, quantitative metrics if developed and validated can add to the information available from standard of care diagnostic imaging. The purpose of this study is to assess the use of quantitative enhancement metrics in predicting the Fuhrman grade of clear cell RCC.
65 multiphase CT examinations with clear cell RCCs were utilized, 44 tumors with Fuhrman grades 1 or 2 and 21 tumors with grades 3 or 4. After tumor segmentation, the following data were extracted: histogram analysis of voxel-based whole lesion attenuation in each phase, enhancement and washout using mean, median, skewness, kurtosis, standard deviation, and interquartile range.
Statistically significant difference was observed in 4 measured parameters between grades 1-2 and grades 3-4: interquartile range of nephrographic attenuation values, standard deviation of absolute enhancement, as well as interquartile range and standard deviation of residual nephrographic enhancement. Interquartile range of nephrographic attenuation values was 292.86 HU for grades 1-2 and 241.19 HU for grades 3-4 (p value 0.02). Standard deviation of absolute enhancement was 41.26 HU for grades 1-2 and 34.66 HU for grades 3-4 (p value 0.03). Interquartile range was 297.12 HU for residual nephrographic enhancement for grades 1-2 and 235.57 HU for grades 3-4 (p value 0.02), and standard deviation of the same was 42.45 HU for grades 1-2 and 37.11 for grades 3-4 (p value 0.04).
Our results indicate that absolute enhancement is more heterogeneous for lower grade tumors and that attenuation and residual enhancement in nephrographic phase is more heterogeneous for lower grade tumors. This represents an important step in devising a predictive non-invasive model to predict the nucleolar grade.
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Salvage ablative therapy (SAT) has been developed as a form of localized treatment for localized recurrence of prostate cancers following radiation therapy. To better address the utility of SAT, prospective clinical trials must address the aspects of accepted standards in the initial evaluation, treatment, follow-up, and outcomes in the oncology community. We undertook this study to achieve consensus on uniform standardized trial design for SAT trials.
A literature search was performed and an international multidisciplinary group of experts was identified. A questionnaire was constructed and sent out to 71 participants in 3 consecutive rounds according to the Delphi method. The project was concluded with a face-to-face meeting in which the results were reviewed and conclusions were formulated.
Patients with recurrent disease after radiation therapy were considered candidates for a SAT trial using any ablation scenario performed with cryotherapy or high-intensity focused ultrasound. It is feasible to compare different sources of energy or to compare with historical data on salvage radical prostatectomy outcomes. The primary objective should be to assess the efficacy of the treatment for negative biopsy rate at 12 months. Secondary objectives should include safety parameters and quality-of-life assessment. Exclusion criteria should include evidence of local or distant metastases. The optimal biopsy strategy is image-guided targeted biopsies. Follow-up includes multiparametric magnetic resonance imaging, prostate-specific antigen level, and quality of life for at least 5 years.
A multidisciplinary board from international experts reached consensus on trial design for SAT in prostate cancer and provides a standard for designing a feasible SAT trial.
[Show abstract][Hide abstract] ABSTRACT: Axl plays multiple roles in tumourigenesis in several cancers. Here we evaluated the expression and biological function of Axl in renal cell carcinoma (RCC).
Axl expression was analysed in a tissue microarray of 174 RCC samples by immunostaining and a panel of 11 normal tumour pairs of human RCC tissues by western blot, as well as in RCC cell lines by both western blot and quantitative PCR. The effects of Axl knockdown in RCC cells on cell growth and signalling were investigated. The efficacy of a humanised Axl targeting monoclonal antibody hMAb173 was tested in histoculture and tumour xenograft.
We have determined by immunohistochemistry (IHC) that Axl is expressed in 59% of RCC array samples with moderate to high in 20% but not expressed in normal kidney tissue. Western blot analysis of 11 pairs of tumour and adjacent normal tissue show high Axl expression in 73% of the tumours but not normal tissue. Axl is also expressed in RCC cell lines in which Axl knockdown reduces cell viability and PI3K/Akt signalling. The Axl antibody hMAb173 significantly induced RCC cell apoptosis in histoculture and inhibited the growth of RCC tumour in vivo by 78%. The hMAb173-treated tumours also had significantly reduced Axl protein levels, inhibited PI3K signalling, decreased proliferation, and induced apoptosis.
Axl is highly expressed in RCC and critical for RCC cell survival. Targeting Axl is a potential approach for RCC treatment.British Journal of Cancer advance online publication, 16 July 2015; doi:10.1038/bjc.2015.237 www.bjcancer.com.
British Journal of Cancer 07/2015; 113(4). DOI:10.1038/bjc.2015.237 · 4.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the impact of 3D printed models of renal tumor on patient's understanding of their conditions. Patient understanding of their medical condition and treatment satisfaction has gained increasing attention in medicine. Novel technologies such as additive manufacturing [also termed three-dimensional (3D) printing] may play a role in patient education.
A prospective pilot study was conducted, and seven patients with a primary diagnosis of kidney tumor who were being considered for partial nephrectomy were included after informed consent. All patients underwent four-phase multi-detector computerized tomography (MDCT) scanning from which renal volume data were extracted to create life-size patient-specific 3D printed models. Patient knowledge and understanding were evaluated before and after 3D model presentation. Patients' satisfaction with their specific 3D printed model was also assessed through a visual scale.
After viewing their personal 3D kidney model, patients demonstrated an improvement in understanding of basic kidney physiology by 16.7 % (p = 0.018), kidney anatomy by 50 % (p = 0.026), tumor characteristics by 39.3 % (p = 0.068) and the planned surgical procedure by 44.6 % (p = 0.026).
Presented herein is the initial clinical experience with 3D printing to facilitate patient's pre-surgical understanding of their kidney tumor and surgery.
World Journal of Urology 07/2015; DOI:10.1007/s00345-015-1632-2 · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To report our 11-year experience of Active Surveillance (AS) program focusing on modern transrectal ultrasound (TRUS)-based monitoring of targeted biopsy-proven cancer lesion.
Consecutive patients on AS, who had targeted biopsy-proven lesion followed by at least a repeat surveillance biopsy and three times TRUS monitoring of the identical visible lesion, were included. Doppler grade of blood flow signal within the lesion was classified from grade 0 to 3. Biopsy-proven progression was defined as upgrade of Gleason score or 25 % or greater increase in cancer core involvement.
Fifty patients were included in this study. Clinical variables (median) included age (61 years), clinical stage (T1c, 42;T2, 8), PSA (4.6 ng/ml), and Gleason score (3 + 3, n = 41;3 + 4, n = 9). Of the 50 patients, 34 demonstrated pathological progression at a median follow-up of 4.4 years. In comparing between without (n = 16) and with (n = 34) pathological progression, there were significant differences in cancer core involvement at entry (p = 0.003), the major axis diameter (p = 0.001) and minor axis diameter (p = 0.001) of the visible lesion at entry, increase in the major axis diameter (p = 0.005) and minor axis diameter (p = 0.013), and upgrade of Doppler grade (p < 0.0001). In multivariate analysis for predicting pathological progression, the increase (≥25 %) in diameter of biopsy-proven lesion (hazard ratio, 15.314; p = 0.023) and upgrade of Doppler grade (hazard ratio, 37.409; p = 0.019) were significant risk factors.
Longitudinal monitoring of the TRUS-visible biopsy-proven cancer provides a new opportunity to perform per-lesion-based AS. The increase in diameter and upgrade of Doppler grade of the lesion were significant risk factors for biopsy-proven progression on AS.
World Journal of Urology 06/2015; DOI:10.1007/s00345-015-1619-z · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To develop a robotic technique for exclusively trans-abdominal control of the supra-hepatic, infra-diaphragmatic inferior vena cava (IVC) to enable level 3 IVC tumor thrombectomy.
Robotic technique was developed in 3 fresh, perfused-model cadavers. Pre-operatively, inflow (right jugular vein) and outflow (left femoral vein) cannulae were inserted and connected to a centrifugal pump to establish a 10 mmHg pressure in the IVC for the water-perfused cadaver model. Using a 5-port trans-peritoneal robotic approach, the falciform ligament was detached from the anterior abdominal wall towards its junction with the diaphragm, and tautly retracted caudally; this adequately retracted the liver caudally as well. Triangular and coronary ligaments were incised, allowing ready visualization of supra-hepatic/infra-diaphragmatic IVC and right/left main hepatic veins. Under direct robotic visualization, IVC was circumferentially mobilized, vessel-looped and controlled.
All 3 robotic procedures were successfully completed trans-abdominally. Average robotic time to control the supra-hepatic IVC was 37min; in each case, the supra-hepatic IVC was circumferentially controlled with a vessel-loop. There were no intraoperative complications. Length of the mobilized supra-hepatic IVC measured between 2-3cm. Right and left supra-hepatic veins were clearly visualized in each case. Necropsy revealed no intra-abdominal/intra-thoracic visceral or vascular injuries to the supra-hepatic IVC, bilateral hepatic veins, or tributaries.
We developed a novel robotic technique for trans-abdominal control of the supra-hepatic infra-diaphragmatic IVC in a perfused human cadaver model. This approach may extend the application of advanced robotic techniques for the performance of major vena caval, hepatic and level 3 IVC renal tumor thrombus surgery.
Journal of endourology / Endourological Society 06/2015; DOI:10.1089/end.2015.0081 · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To discuss the evaluation of the enhancement curve over time of the major renal cell carcinoma (RCC) subtypes, oncocytoma, and lipid-poor angiomyolipoma, to aid in the preoperative differentiation of these entities. Differentiation of these lesions is important, given the different prognoses of the subtypes, as well as the desire to avoid resecting benign lesions.
We discuss findings from CT, MR, and US, but with a special emphasis on contrast-enhanced ultrasound (CEUS). CEUS technique is described, as well as time-intensity curve analysis.
Examples of each of the major RCC subtypes (clear cell, papillary, and chromophobe) are shown, as well as examples of oncocytoma and lipid-poor angiomyolipoma. For each lesion, the time-intensity curve of enhancement on CEUS is reviewed, and correlated with the enhancement curve over time reported for multiphase CT and MR.
Preoperative differentiation of the most common solid renal masses is important, and the time-intensity curves of these lesions show some distinguishing features that can aid in this differentiation. The use of CEUS is increasing, and as a modality it is especially well suited to the evaluation of the time-intensity curve.
[Show abstract][Hide abstract] ABSTRACT: Amongst nephron-sparing modalities, partial nephrectomy (PN) is the standard of care in the treatment of renal cell carcinoma (RCC). Despite the increasing utilization of PN, particularly propagated by robot-assisted, minimally invasive approaches for small renal masses (SRMs), the limits of PN appear to be also evolving. In this review, we sought to address the tumour stage beyond which PN may be oncologically perilous. While the evidence supports PN in the treatment of tumours < pT2a, PN may have a role in advanced or metastatic RCC. Other scenarios wherein PN has limited utility are also explored, including anatomical or surgical factors that dictate the difficulty of the case, such as prior renal surgery. Lastly, we discuss the emerging role of molecular biomarkers, specifically epigenetics, to aid in the risk stratification of SRMs and to select tumours optimally suited for PN.
Translational Andrology and Urology 06/2015; 4(3):294-300. DOI:10.3978/j.issn.2223-4683.2015.06.04
[Show abstract][Hide abstract] ABSTRACT: To describe our approach for port placement and robot docking for pelvic and kidney surgery (KS).
We utilize a four-arm robotic approach and a 5-6 port placement consisting of: 1- 12 mm camera port, 3- 8 mm robotic ports, and 1 to 2 assistant ports. For radical prostatectomy, the working robotic ports run parallel below the level of the umbilicus. Radical cystectomy ports are more cephalad and above the level of the umbilicus. For transperitoneal KS, two bariatric robotic ports are used, aiming for an equilateral triangle configuration. With retroperitoneal (RN) KS, a balloon dilator and balloon port create the RN space; bariatric ports comprise the most anterior and posterior ports.
This technique has been utilized since 2010 on over 2,370 robotic urologic cases. To date, no procedure has required patient or robot positioning while maintaining 4th arm functionality with minimal robotic arm clashing.
Our approach of port placement and robot docking is reproducible and feasible for pelvic and kidney surgery.
Journal of endourology / Endourological Society 04/2015; DOI:10.1089/end.2015.0077 · 1.71 Impact Factor