Joseph L Chin

Lawson Health Research Institute, London, Ontario, Canada

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Publications (236)813.42 Total impact

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    ABSTRACT: Background:Bicalutamide is a widely used, relatively non-toxic anti-androgen, particularly when used in combination with androgen deprivation. In men on combined androgen blockade (CAB), the typical dose is 50 mg per day. For men receiving monotherapy with bicalutamide anti-androgen, the dose is 150 mg per day. The objective was to determine the PSA response rate to increasing bicalutamide to 150 mg per day in men who develop castrate-resistant prostate cancer (CRPC) on CAB with goserelin acetate and bicalutamide 50 mg per day.Methods:A national, multicentre, phase 2, open-label study in men on CAB with a rising PSA>2.0. The primary end point of the trial was PSA response at 12 months, defined as a decline by 50% or more compared with baseline value. Partial response was defined as a PSA decline of 10-49%. Secondary end points were duration of PSA response, change in slope of serum PSA, change in ratio of free PSA: total PSA at 3 months, 6 months and 12 months as compared with baseline; duration of the bicalutamide withdrawal response after discontinuation; the rate of cardiovascular events; and toxicity. The study was initially planned to accrue 100 patients, but was closed early due to diminishing accrual.Results:Sixty-four patients were accrued; 61 patients received trial treatment and constituted the intention-to-treat (ITT) cohort. 70% were M0. Among 59 evaluable ITT patients, 13 (22%) patients had a >50% PSA decline, 5 (8%) had a decline between 10 and 50%, 4 (7%) had stabilization and 37 (63%) had PSA progression. The median duration was 3.7 months (95% confidence interval of 0.92-6.21 months).Conclusion:In patients with early biochemical failure on CAB with bicalutamide 50 mg, an increase in dose to 150 mg of bicalutamide resulted in a PSA response of ⩾50% in 22% of patients. Toxicity was mild. Bicalutamide dose intensification may benefit a subset of patients with CRPC. We believe this relatively inexpensive approach warrants further evaluation.Prostate Cancer and Prostatic Disease advance online publication, 2 September 2014; doi:10.1038/pcan.2014.24.
    Prostate cancer and prostatic diseases. 09/2014;
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    ABSTRACT: BIRC is focused on the discovery and development of innovative imaging techniques and instrumentation to improve the understanding, diagnosis, and treatment of human diseases. By integrating efforts across multiple Faculties, University Departments and Institutes, the Centre has the potential to become the most successful integrated Biomedical Imaging Research Program in Canada, and to rank among the top 5 such programs in the world. http://www.birc.ca/ As part of its evaluation of imaging techniques, the CIHR team participated in the development of a new type of PET imaging agent for prostate cancer, 18F-Fluorocholine. London was the first centre in Ontario to use this agent.
    08/2014; BIRC - Western University - London - ON - Canada - CIHR Prostate Cancer Team Grant (2008-2014).
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    ABSTRACT: Optimal oncologic control of higher stage prostate cancers often requires sacrificing the neurovascular bundles (NVB) with subsequent postoperative erectile dysfunction (ED), which can be treated with interposition graft using sural nerve.
    Journal of Sexual Medicine 06/2014; · 3.51 Impact Factor
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    ABSTRACT: To evaluate risk factors for bladder cancer recurrence in a cohort of patients treated with radical nephroureterectomy (RNU).
    Urologic oncology. 05/2014;
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    ABSTRACT: Purpose: Multiparametric magnetic resonance imaging (MPMRI) supports detection and staging of prostate cancer, but the image characteristics needed for tumor boundary delineation to support focal therapy have not been widely investigated. We quantified the detectability (image contrast between tumor and non-cancerous contralateral tissue) and the localizability (image contrast between tumor and non-cancerous neighboring tissue) of Gleason score 7 (GS7) peripheral zone (PZ) tumors on MPMRI using tumor contours mapped from histology using accurate 2D-3D registration. Methods: MPMRI [comprising T2-weighted (T2W), dynamic-contrast-enhanced (DCE), apparent diffusion coefficient (ADC) and contrast transfer coefficient images] and post-prostatectomy digitized histology images were acquired for 6 subjects. Histology contouring and grading (approved by a genitourinary pathologist) identified 7 GS7 PZ tumors. Contours were mapped to MPMRI images using semi-automated registration algorithms (combined target registration error: 2 mm). For each focus, three measurements of mean +/- standard deviation of image intensity were taken on each image: tumor tissue (mT+/-sT), non-cancerous PZ tissue < 5 mm from the tumor (mN+/-sN), and non-cancerous contralateral PZ tissue (mC+/-sC). Detectability [D, defined as mT-mC normalized by sT and sC added in quadrature] and localizability [L, defined as mT-mN normalized by sT and sN added in quadrature] were quantified for each focus on each image. Results: T2W images showed the strongest detectability, although detectability |D|>=1 was observed on either ADC or DCE images, or both, for all foci. Localizability on all modalities was variable; however, ADC images showed localizability |L|>=1 for 3 foci. Conclusions: Delineation of GS7 PZ tumors on individual MPMRI images faces challenges; however, images may contain complementary information, suggesting a role for fusion of information across MPMRI images for delineation.
    02/2014;
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    ABSTRACT: Measurement of prostate tumour volume can inform prognosis and treatment selection, including an assessment of the suitability and feasibility of focal therapy, which can potentially spare patients the deleterious side effects of radical treatment. Prostate biopsy is the clinical standard for diagnosis but provides limited information regarding tumour volume due to sparse tissue sampling. A non-invasive means for accurate determination of tumour burden could be of clinical value and an important step toward reduction of overtreatment. Multi-parametric magnetic resonance imaging (MPMRI) is showing promise for prostate cancer diagnosis. However, the accuracy and inter-observer variability of prostate tumour volume estimation based on separate expert contouring of T2-weighted (T2W), dynamic contrastenhanced (DCE), and diffusion-weighted (DW) MRI sequences acquired using an endorectal coil at 3T is currently unknown. We investigated this question using a histologic reference standard based on a highly accurate MPMRIhistology image registration and a smooth interpolation of planimetric tumour measurements on histology. Our results showed that prostate tumour volumes estimated based on MPMRI consistently overestimated histological reference tumour volumes. The variability of tumour volume estimates across the different pulse sequences exceeded interobserver variability within any sequence. Tumour volume estimates on DCE MRI provided the lowest inter-observer variability and the highest correlation with histology tumour volumes, whereas the apparent diffusion coefficient (ADC) maps provided the lowest volume estimation error. If validated on a larger data set, the observed correlations could support the development of automated prostate tumour volume segmentation algorithms as well as correction schemes for tumour burden estimation on MPMRI.
    02/2014;
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    ABSTRACT: To evaluate the effect of body mass index (BMI) on the outcomes of patients with urinary tract carcinoma treated with radical surgery. Data were collected from 10 Canadian centers on patients who underwent radical cystectomy (RC) (1998-2008) or radical nephroureterectomy (RNU) (1990-2010). Various parameters among subsets of patients (BMI<25, 25≤BMI<30, and BMI≥30kg/m(2)) were analyzed. Kaplan-Meier and multivariate analyses were performed to assess the effect of BMI on overall survival, disease-specific survival, and recurrence-free survival (RFS). Among the 847 RC and 664 RNU patients, there was no difference in histology, stage, grade, and margin status among the 3 patient subsets undergoing either surgery. However, RC patients with lower BMIs (<25kg/m(2)) were significantly older (P = 0.004), had more nodal metastasis (P = 0.03), and trended toward higher stage (P = 0.052). RNU patients with lower BMIs (<25kg/m(2)) were significantly older (P = 0.0004) and fewer received adjuvant chemotherapy (P = 0.04) compared with those with BMI≥30kg/m(2); however, there was no difference in tumor location (P = 0.20), stage (P = 0.48), and management of distal ureter among the groups (P = 0.30). On multivariate analysis, BMI was not prognostic for overall survival, disease-specific survival, and RFS in the RC group. However, BMI≥30kg/m(2) was associated with more bladder cancer recurrences and worse RFS in the RNU group (HR = 1.588; 95% CI: 1.148-2.196; P = 0.0052). Increased BMI did not influence survival among RC patients. BMI≥30kg/m(2) is associated with worse bladder cancer recurrences among RNU patients; whether this is related to difficulty in obtaining adequate bladder cuff in patients with obesity requires further evaluation.
    Urologic Oncology 01/2014; · 3.65 Impact Factor
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    ABSTRACT: Objective To evaluate risk factors for bladder cancer recurrence in a cohort of patients treated with radical nephroureterectomy (RNU). Patients and methods At 10 Canadian University Centers, we retrospectively evaluated data, between 1990 and 2010, from 743 patients who were free from bladder cancer and were previously treated with RNU for upper tract urothelial cancer. Results Of 743 patients, 167 (22.5%) developed bladder tumors after a median time of 17.2 months after RNU. Multivariable analysis detected age (hazard ratio [HR] = 1.028; 95% CI: 1.010–1.046; P = 0.0018), tumor location in both the renal pelvis and the ureter (HR = 2.205; 95% CI: 1.355–3.589; P = 0.0015), the use of adjuvant systemic chemotherapy (HR = 2.309; 95% CI: 1.439–3.705; P = 0.0005), and laparoscopic surgery (HR = 1.876; 95% CI: 1.226–2.87; P = 0.0037) as risk factors for bladder cancer recurrence. Open excision of a bladder cuff (HR = 0.661; 95% CI: 0.453–0.965; P = 0.0319) and transurethral resection of the intramural ureter (HR = 0.548; 95% CI: 0.306–0.981; P = 0.0429) on comparison with extravesical resection decreased the risk of bladder cancer recurrence significantly. Major limitations were the retrospective design and partially missing data, although the significance of variables did not change in the imputation analysis. Conclusion Older patients, those with tumor location in both the renal pelvis and the ureter, and those treated with adjuvant systemic chemotherapy were found at higher risk for intravesical recurrence, as were those having undergone extravesical ureterectomy or laparoscopic RNU.
    Urologic Oncology: Seminars and Original Investigations. 01/2014;
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    ABSTRACT: Most small renal masses (SRMs) are diagnosed incidentally and have a low malignant potential. As more elderly patients and infirm patients are diagnosed with SRMs, there is an increased interest in active surveillance (AS) with delayed intervention. Patient and tumour characteristics relating to aggressive disease have not been well-studied. The objective was to determine predictors of growth of SRMs treated with AS. A multicentre prospective phase 2 clinical trial was conducted on 207 SRMs in 169 patients in 8 institutions in Canada from 2004 to 2009; in these patients treatment was delayed until disease progression. Patient and tumour characteristics were evaluated to determine predictors of growth of SRMs by measuring rates of change in growth (on imaging) over time. All patients underwent AS for presumed renal cell carcinoma (RCC) based on diagnostic imaging. We used the following factors to develop a predictive model of tumour growth with binary recursive partitioning analysis: patient characteristics (age, symptoms at diagnosis) and tumour characteristics (consistency [solid vs. cystic] and maximum diameter at diagnosis. With a median follow-up of 603 days, 169 patients (with 207 SRMs) were followed prospectively. Age, symptoms at diagnosis, tumour consistency and maximum diameter of the renal mass were not predictors of growth. This cohort was limited by lack of availability of patient and tumour characteristics, such as sex, degree of endophytic component and tumour location. Slow growth rates and the low malignant potential of SRMs have led to AS as a treatment option in the elderly and infirm population. In a large prospective cohort, we have shown that age, symptoms, tumour consistency and maximum diameter of the mass at diagnosis are not predictors of growth of T1a lesions. More knowledge on predictors of growth of SRMs is needed.
    Canadian Urological Association journal = Journal de l'Association des urologues du Canada 01/2014; 8(1-2):24-7. · 1.66 Impact Factor
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    ABSTRACT: Normal physiology relies on the organization of transmembrane proteins by molecular scaffolds, such as tetraspanins. Oncogenesis frequently involves changes in their organization or expression. The tetraspanin CD151 is thought to contribute to cancer progression through direct interaction with the laminin-binding integrins α3β1 and α6β1. However, this interaction cannot explain the ability of CD151 to control migration in the absence of these integrins or on non-laminin substrates. We demonstrate that CD151 can regulate tumor cell migration without direct integrin binding and that integrin-free CD151 (CD151free) correlates clinically with tumor progression and metastasis. Clustering CD151free through its integrin-binding domain promotes accumulation in areas of cell-cell contact leading to enhanced adhesion and inhibition of tumor cell motility in vitro and in vivo. CD151free clustering is a strong regulator of motility even in the absence of α3 expression but requires PKCα, suggesting that CD151 can control migration independent of its integrin associations. The histological detection of CD151free in prostate cancer correlates with poor patient outcome. When CD151free is present, patients are more likely to recur after radical prostatectomy and progression to metastatic disease is accelerated. Multivariable analysis identifies CD151free as an independent predictor of survival. Moreover, the detection of CD151free can stratify survival among patients with elevated PSA. Cumulatively these studies demonstrate that a subpopulation of CD151 exists on the surface of tumor cells that can regulate migration independent of its integrin partner. The clinical correlation of CD151free with prostate cancer progression suggests that it may contribute to the disease and predict cancer progression.
    Cancer Research 11/2013; · 9.28 Impact Factor
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    ABSTRACT: To evaluate the impact of concomitant carcinoma in situ (CIS) on upstaging and outcome of patients treated with radical cystectomy with pelvic lymph node dissection. We collected and pooled a database of 1,968 patients who have undergone radical cystectomy between 1998 and 2008 in eight academic centers across Canada. Collected variables included patient's age, gender, tumor grade, histology and the presence of concomitant CIS with either cTa-1 or cT2 disease, dates of recurrence and death. In the presence of concomitant CIS, upstaging following radical cystectomy occurred in 48 and 55 % of patients with cTa-1 and cT2 disease, respectively. On univariate analysis, the presence of concomitant CIS with cT2 disease was associated with upstaging (p < 0.0001), and the presence of concomitant CIS with cTa-1 disease was also associated with upstaging but did not reach statistical significance (p = 0.0526). On multivariate analyses, the presence of concomitant CIS with either cTa-1 or cT2 tumors was independently prognostic of disease upstaging (p = 0.0001 and 0.0186, respectively). However, on multivariate analysis that incorporates pathologic stage, concomitant CIS was not significantly associated with worse overall, recurrence-free or disease-specific survival. These results demonstrate that while the presence of concomitant CIS on cystectomy specimens does not independently affect outcomes, its presence is significantly predictive of a higher rate of upstaging at radical cystectomy.
    World Journal of Urology 11/2013; · 2.89 Impact Factor
  • Joseph L Chin
    European Urology 10/2013; · 10.48 Impact Factor
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    ABSTRACT: Purpose: Evaluation of in vivo prostate imaging modalities for determining the spatial distribution and aggressiveness of prostate cancer ideally requires accurate registration of images to an accepted reference standard, such as histopathological examination of radical prostatectomy specimens. Three-dimensional (3D) reconstruction of prostate histology facilitates these registration-based evaluations by reintroducing 3D spatial information lost during histology processing. Because the reconstruction accuracy may constrain the clinical questions that can be answered with these data, it is important to assess the tradeoffs between minimally disruptive methods based on intrinsic image information and potentially more robust methods based on extrinsic fiducial markers.Methods: Ex vivo magnetic resonance (MR) images and digitized whole-mount histology images from 12 radical prostatectomy specimens were used to evaluate four 3D histology reconstruction algorithms. 3D reconstructions were computed by registering each histology image to the corresponding ex vivo MR image using one of two similarity metrics (mutual information or fiducial registration error) and one of two search domains (affine transformations or a constrained subset thereof). The algorithms were evaluated for accuracy using the mean target registration error (TRE) computed from homologous intrinsic point landmarks (3-16 per histology section; 232 total) identified on histology and MR images, and for the sensitivity of TRE to rotational, translational, and scaling initialization errors.Results: The algorithms using fiducial registration error and mutual information had mean ± standard deviation TREs of 0.7 ± 0.4 and 1.2 ± 0.7 mm, respectively, and one algorithm using fiducial registration error and affine transforms had negligible sensitivities to initialization errors. The postoptimization values of the mutual information-based metric showed evidence of errors due to both the optimizer and the similarity metric, and variation of parameters of the mutual information-based metric did not improve its performance.Conclusions: The extrinsic fiducial-based algorithm had lower mean TRE and lower sensitivity to initialization than the intrinsic intensity-based algorithm using mutual information. A model relating statistical power to registration error for certain imaging validation study designs estimated that a reconstruction algorithm with a mean TRE of 0.7 mm would require 27% fewer subjects than the method used to initialize the algorithms (mean TRE 1.3 ± 0.7 mm), suggesting the choice of reconstruction technique can have a substantial impact on the design of imaging validation studies, and on their overall cost.
    Medical Physics 09/2013; 40(9):093501. · 2.91 Impact Factor
  • European Urology 06/2013; · 10.48 Impact Factor
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    ABSTRACT: While PDE5 inhibitors have revolutionized treatment of ED, approximately 30% of patients are non-responsive. A significant cause of this is vascular and smooth muscle dysfunction, as well as nerve atrophy. Autologous administration of bone marrow mononuclear cells (BMMC) has been performed in over 2000 cardiac patients without adverse effects, for stimulation of angiogenesis/regeneration. Despite its ease of access, and dependence on effective vasculature for function, comparatively little has been perform in terms of BMMC therapy for ED. Here we outline the rationale for use of autologous BMMC in patients with ED, as well as provide early safety data on the first use of this procedure clinically.
    Journal of Translational Medicine 06/2013; 11(1):139. · 3.46 Impact Factor
  • Joseph L Chin
    The Journal of urology 04/2013; · 4.02 Impact Factor
  • Joseph L Chin
    European Urology 04/2013; · 10.48 Impact Factor
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    ABSTRACT: Clinical variables with more accuracy to predict biologically insignificant prostate cancer are needed. We evaluated the combination of transrectal ultrasound-guided biopsy of the prostate (TRUSBx) pathologic and radiologic findings in their ability to predict the biologic potential of each prostate cancer. A total of 1043 consecutive patients who underwent TRUSBx were reviewed. Using pathologic criteria, patients with prostate cancer (n = 529) and those treated with radical prostatectomy (RP) (n = 147) were grouped as: "insignificant" (Gleason score ≤ 6, prostate-specific antigen (PSA) density ≤ 0.15 ng/ml, tumor in ≤ 50% of any single core, and < 33% positive cores) and "significant" prostate cancer. TRUSBx imaging and pathology results were compared with the RP specimen to identify factors predictive of "insignificant" prostate cancer. TRUSBx pathology results demonstrated perineural invasion in 36.4% of "significant" versus 5.4% of "insignificant" prostate cancers (p < 0.01) and pathologic invasion of periprostatic tissue in 7% of significant versus 0% of insignificant prostate cancers (p < 0.01). TRUS findings concerning for neoplasia were associated with significant tumors (p < 0.01). Multivariable analysis demonstrated perineural invasion in the biopsy specimen (p = 0.03), PSA density (p = 0.02) and maximum tumor volume of any core (p = 0.02) were independently predictive of a significant prostate cancer. TRUS findings concerning for measurable tumor and perineural invasion in TRUSBx specimens appear to be complementary to Epstein's pathologic criteria and should be considered to aid in the determination whether a prostate cancer is organ-confined and more likely to be biologically insignificant.
    The Canadian Journal of Urology 04/2013; 20(2):6696-701. · 0.74 Impact Factor
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    ABSTRACT: OBJECTIVES: Whether a patient has urothelial carcinoma located within the renal pelvis or ureter remains a controversial prognostic indicator in clinical urology. We wished to evaluate whether tumor location is associated with recurrence in patients undergoing nephroureterectomy for upper tract urothelial cancer in a large volume patient cohort. SUBJECTS AND METHODS: We created a retrospective database of patients from 7 academic centers throughout Canada who underwent nephroureterectomy for upper tract urothelial carcinoma. Patient demographics as well as pathologic and surgical factors were analyzed to evaluate any statistical association between tumor location and overall survival, disease-free survival, and disease-specific survival. RESULTS: A total of 1,029 patients had data available for analysis with a mean follow up of 3.2 years. Kaplan Meier 5-year disease-free survivals (DFS) were 46%, 37%, and 19% for renal pelvis tumors, ureteric tumors, and multifocal tumors respectively. There was no association between the location of the tumor and the DFS, however, disease involving both the ureter and renal pelvis was associated with lower DFS and overall survival (OS) (P < 0.001). CONCLUSIONS: Tumor location does not appear to have any influence on the risk of recurrence of disease following nephroureterectomy in this large patient cohort. However, multifocal tumors involving both the ureter and renal pelvis had a significantly worse prognosis and should be considered for more aggressive management.
    Urologic Oncology 02/2013; · 3.65 Impact Factor
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    ABSTRACT: We review the current evidence for the role of low-dose rate brachytherapy (PB) in patients with low- or intermediate-risk prostate cancer using a systematic review of the literature. We searched MEDLINE and EMBASE (from January 1996 to October 2011), the Cochrane Library, relevant guideline web-sites, and websites for meetings specific for genitourinary diseases. Ten systematic reviews and 55 single-study papers met the pre-planned study selection criteria. In the end, 36 articles were abstracted and analyzed for this systematic review. There is no evidence for a difference in efficacy between PB and external beam radiation therapy (EBRT), or between PB and radical prostatectomy (RP). During the 6 months to 3 years after treatment, PB was associated with less urinary incontinence and sexual impotency than RP, and RP was associated with less urinary irritation and rectal morbidity than PB. However, these differences diminished over time. PB conferred less risk of impotency and rectal morbidity in the three years after treatment than EBRT. Iodine-125 and alladium-103 did not differ with respect to biochemical relapse-free survival and patient-reported outcomes. PB alone is a treatment option with equal efficacy to EBRT or RP alone in patients with newly diagnosed low- or intermediate-risk prostate cancer who require or choose active treatment.
    Canadian Urological Association journal = Journal de l'Association des urologues du Canada 01/2013; 7(11-12):463-470. · 1.66 Impact Factor

Publication Stats

5k Citations
813.42 Total Impact Points

Institutions

  • 2014
    • Lawson Health Research Institute
      London, Ontario, Canada
  • 2009–2014
    • University of Toronto
      • Division of Urology
      Toronto, Ontario, Canada
  • 1988–2014
    • The University of Western Ontario
      • • Schulich School of Medicine and Dentistry
      • • Division of Urology
      • • Department of Surgery
      • • Department of Pathology
      London, Ontario, Canada
  • 2013
    • University of Alberta
      Edmonton, Alberta, Canada
  • 2010–2013
    • McGill University
      • Department of Neurology and Neurosurgery
      Montréal, Quebec, Canada
    • University of Sydney
      Sydney, New South Wales, Australia
  • 2012
    • Sunnybrook Health Sciences Centre
      Toronto, Ontario, Canada
    • The Second Xiangya Hospital of Central South University
      Ch’ang-sha-shih, Hunan, China
    • Dalhousie University
      • Department of Urology
      Halifax, Nova Scotia, Canada
  • 2007–2012
    • Robarts Research Institute
      • Imaging Research Laboratories
      London, Ontario, Canada
    • Centre hospitalier de l'Université de Montréal (CHUM)
      Montréal, Quebec, Canada
  • 1998–2012
    • London Health Sciences Centre
      London, Ontario, Canada
  • 2011
    • University College London Hospitals NHS Foundation Trust
      • Department of Urology
      Londinium, England, United Kingdom
  • 2006–2009
    • University of Texas Health Science Center at San Antonio
      • • Department of Urology
      • • Department of Radiation Oncology
      San Antonio, TX, United States
  • 1996–2005
    • Regional Integration Cancer Center
      Мендоса, Mendoza, Argentina
  • 1993
    • Kitasato University
      • Department of Pharmaceutical Sciences
      Edo, Tōkyō, Japan