Ashutosh Tewari

National Yang Ming University, T’ai-pei, Taipei, Taiwan

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Publications (310)1391.2 Total impact

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    ABSTRACT: In 2010, we published a review summarising the available literature on surgical anatomy of the prostate and adjacent structures involved in cancer control and the functional outcome of prostatectomy.
    No preview · Article · Feb 2016 · European Urology
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    ABSTRACT: Summary There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or mutations (SPOP, FOXA1, and IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defects.
    Full-text · Article · Nov 2015 · Cell
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    ABSTRACT: Introduction and objectives: Following the recently published EAU Policy on Live Surgical Events (LSE’s), it is now assured that live surgery will be ongoing at conferences in the immediate future. However, the panel reached >80% consensus on the view that performing at a home institution may be safer. The committee also identified issues with a ‘‘travelling surgeon’’ performing complex surgery in an unfamiliar environment with a surgical team that is not experienced with the intricacies of the surgeon’s technique. LSE’s from a home institution remove or minimize these negative aspects. Furthermore, there are other important reasons why LSE’s are enhanced when performed at a high- volume home institution. The potential to optimise surgical performance comes from working with an experienced team. Consistency is a key measure of quality, and robotic surgery in particular epitomises teamwork. It is therefore likely that the natural evolution of LSE’s, is that a greater proportion are broadcast from home institutions. We aimed to highlight the benefits of this approach to surgical training with a global approach. Material and methods: On the 16-17th February 2015 ten robotic centers from 4 continents broadcast live surgery over a 24hr continuous period. The event was advised by and approved by the EAU live surgery committee. The live surgery was broadcast on a website www.wrse24.org which was accessible only to professionals, being password protected and requiring registration and approval. LiveArena provided the infrastructure and technological support. The event was promoted via social media including a BJUI blog and a poll carried out by the BJUI website posing the question “would you sign up for a surgical webinar, instead of travelling to the venue if you received the same Continuous Medical Education (CME) points?” Results: We had registrants from 61 countries in total (58 on the day). Accessing the live surgery included 469 registrants from Europe, 114 from the US, 267 from Asia, 114 from Australia and 12 from Africa. Unique viewers were classified as viewers using a unique IP address. We had 1390 unique viewers to the www.wrse24.org website over the live 24 hours and this number increased to 2277 over the next 6 days. 76% of respondents to the BJUI poll said that they would ‘attend’ a streamed virtual surgical conference instead of travelling to it, if they got the same CME accreditation. Conclusions: This was the largest global robotic webinar for live surgery. Indications are that it was well received by the worldwide audience. Planned improvements to future WRSE24 events include further integration of social media for direct real-time interaction between surgeons and the viewers, and increased functionality and interaction with the video library.
    No preview · Article · Sep 2015 · European Urology Supplements
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    ABSTRACT: We analyzed pentafecta outcomes [complication-free, continence, potency, negative surgical margins (NSM)], biochemical recurrence (BCR)-free] of 230 patients undergoing robotic-assisted radical prostatectomy (RARP) with bilateral neurovascular (NVB) preservation. Patient outcomes (group I, cases 1-115; group II, cases 116-230) were assessed prospectively. Definitions were: continence, using no pads; potency, ability to achieve/maintain erections firm enough for sexual intercourse; positive surgical margin, presence of tumor tissue on inked specimen surface; and BCR, two consecutive PSA levels >0.2 ng/ml after RALP. The mean patient age was 62.5 years, mean PSA=8.62 ng/ml. The complication-free rate was 93.9% (216/230), continence rate 98.3% (226/230), potency 86.1% (198/230), NSM 77.0% (177/230) and BCR-free 92.6% (213/230). The trifecta rate (continence, potency, BCR-free) was 81.7% (188/230). The pentafecta rate was 60.4% (139/230). Pentafecta is the new standard of outcomes for RARP with bilateral NVB, with patient selection and reduced positive surgical margins attaining best outcomes. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
    Full-text · Article · Sep 2015 · Anticancer research
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    ABSTRACT: Site-dependent and interindividual histological differences in Denonvilliers' fascia (DF) are not well understood. This study aimed to examine site-dependent and interindividual differences in DF and to determine whether changes in the current approach to radical prostatectomy are warranted in light of these histological findings. Twenty-five donated male cadavers (age range, 72-95 years) were examined. These cadavers had been donated to Sapporo Medical University for research and education on human anatomy. Their use for research was approved by the university ethics committee. Horizontal sections (15 cadavers) or sagittal sections (10 cadavers) were prepared at intervals of 2-5 mm for hematoxylin and eosin staining. Elastic-Masson staining and immunohistochemical staining were also performed, using mouse monoclonal anti-human alpha-smooth muscle actin to stain connective tissues and mouse monoclonal anti-human S100 protein to stain nerves. We observed that DF consisted of disorderly, loose connective tissue and structures resembling "leaves", which were interlacing and adjacent to each other, actually representing elastic or smooth muscle fibers. Variations in DF were observed in the following: 1) configuration of multiple leaves, including clear, unclear, or fragmented behind the body and tips of the seminal vesicles, depending on the site; 2) connection with the lateral pelvic fascia at the posterolateral angle of the prostate posterior to the neurovascular bundles, being clear, unclear, or absent; 3) all or most leaves of DF fused with the prostatic capsule near the base of the seminal vesicles, and periprostatic nerves were embedded in the leaves at the fusion site; and 4) some DF leaves fused with the prostatic capsule anteriorly and/or the fascia propria of the rectum posteriorly. Site-dependent and interindividual variations in DF were observed in donated elderly male cadavers. All or most DF leaves are fused with the prostatic capsule near the base of the seminal vesicles and some DF leaves are fused with the fascia propria of the rectum posterior. Based on our results, surgeons should be aware of variations and search for them to create a suitable dissection plane to avoid iatrogenic positive margins and rectal injury.
    Full-text · Article · May 2015 · BMC Urology
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    ABSTRACT: Treatment possibilities for clinically localised prostate cancer include radical prostatectomy (RP), external beam radiotherapy, brachytherapy, focal therapy and active surveillance. Conflicting and methodologically flawed observational data from the last two decades have led to uncertainty as to the best oncological option. However, recently, there has been a series of high-quality studies that point to disease specific and overall survival advantages for those men undergoing RP. This article reviews the latest evidence and argues that at the current time, RP must be considered the gold standard treatment for the majority of men with clinically localised prostate cancer.
    No preview · Article · May 2015 · Current Urology Reports
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    Adnan Ali · Nelson Stone · Richard Stock · Ashutosh Tewari

    Preview · Article · Apr 2015 · The Journal of Urology
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    Shalini S Yadav · Jinyi Li · Hugh J Lavery · Kamlesh K Yadav · Ashutosh K Tewari
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    ABSTRACT: Next-generation sequencing (NGS) of the genetic information of cancer cells has revolutionized the field of cancer biology, including prostate cancer (PCa). New recurrent alterations have been identified in PCa (e.g., TMPRSS2-ERG translocation, SPOP and CHD1 mutations, and chromoplexy), and many previous ones in well-established pathways have been validated (e.g., androgen receptor overexpression and mutations; PTEN, RB1, and TP53 loss/mutations). With its highly heterogeneous nature, PCa continues to pose a tremendous challenge in terms of diagnosis and prognosis. Combining the information gained through NGS studies with clinicopathological and radiological data will help diagnose the aggressiveness of the cancer with greater accuracy. Furthermore, understanding the heterogeneity of tumor through single-cell or single-molecule sequencing technology will also strengthen the prognosis and provide better, patient-specific drug identification. As this research becomes more prominent, it is important that urologic oncologists become familiar with the various NGS technologies and the results generated using them. We highlight the commonly used NGS tools and summarize recent discoveries relevant to PCa. Copyright © 2015 Elsevier Inc. All rights reserved.
    Full-text · Article · Mar 2015 · Urologic Oncology
  • Rao S. Mandalapu · Adnan Ali · Sailaja Pisipati · Ashutosh K. Tewari
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    ABSTRACT: Benign prostatic hyperplasia is the most common benign neoplasm in American men, affecting nearly 6.5 million men aged 50-79 years in the United States. The treatment options for clinically significant benign prostatic hyperplasia have dramatically changed in the recent past with the development of minimally invasive procedures and advanced medical therapies. However, open prostatectomy remains the surgery of choice in selected patients. Simple prostatectomy used to be the primary treatment of choice for symptomatic patients with benign prostatic hyperplasia (BPH). In an attempt to reduce the length of hospital stay and morbidity associated with open prostatectomy, minimally invasive approaches have evolved. Robot-assisted simple prostatectomy (RASP) holds potential for improving perioperative outcomes following simple prostatectomy. In this chapter we briefly describe the indications, contraindications, prevalent techniques, and complications of RASP.
    No preview · Article · Jan 2015
  • Adnan Ali · Bachir Taouli · Ashutosh K. Tewari
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    ABSTRACT: Conventional imaging modalities that demonstrate anatomical information fail to yield accurate information for diagnosis, staging and selection of treatment or effective monitoring of prostate cancer. Fortunately this has changed with newer imaging techniques that focus on functional and metabolic imaging, providing quantitative information and allowing investigation into changes that occur at a cellular level in prostate cancer. Multiparametric MRI combines the anatomical and functional domains of imaging to achieve this goal. Currently, the histopathological diagnosis of prostate cancer is based on transrectal ultrasound-guided biopsy, which has limited sensitivity. Technical improvements in MRI have resulted in the use of MRI to target prostate biopsies. This chapter presents a perspective on the optimal role of multiparametric MRI in prostate cancer detection and its use in targeted biopsies.
    No preview · Article · Jan 2015
  • Ashutosh K Tewari

    No preview · Article · Dec 2014 · The Journal of Urology
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    ABSTRACT: Multiphoton microscopy can instantly visualize cellular details in unstained tissues. Multiphoton probes with clinical potential have been developed. This study evaluates the suitability of multiphoton gradient index (GRIN) endoscopy as a diagnostic tool for prostatic tissue. A portable and compact multiphoton endoscope based on a 1-mm diameter, 8-cm length GRIN lens system probe was used. Fresh ex vivo samples were obtained from 14 radical prostatectomy patients and benign and malignant areas were imaged and correlated with subsequent H&E sections. Multiphoton GRIN endoscopy images of unfixed and unprocessed prostate tissue at a subcellular resolution are presented. We note several differences and identifying features of benign versus low-grade versus high-grade tumors and are able to identify periprostatic tissues such as adipocytes, periprostatic nerves, and blood vessels. Multiphoton GRIN endoscopy can be used to identify both benign and malignant lesions in ex vivo human prostate tissue and may be a valuable diagnostic tool for real-time visualization of suspicious areas of the prostate.
    Full-text · Article · Nov 2014 · Journal of Biomedical Optics
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    ABSTRACT: Objective: Several smaller single-center studies have reported a prognostic role for Ki-67 labeling index in prostate cancer. Our aim was to test whether Ki-67 is an independent prognostic marker of biochemical recurrence (BCR) in a large international cohort of patients treated with radical prostatectomy (RP). Methods: Ki-67 immunohistochemical staining on prostatectomy specimens from 3,123 patients who underwent RP for prostate cancer was retrospectively performed. Univariable and multivariable Cox regression models were used to assess the association of Ki-67 status with BCR. Results: Ki-67 positive status was observed in 762 (24.4 %) patients and was associated with lymph node involvement (LNI) (p = 0.039). Six hundred and twenty-one (19.9 %) patients experienced BCR. The estimated 3-year biochemical-free survivals were 85 % for patients with negative Ki-67 status and 82.1 % for patients with positive Ki-67 status (log-rank test, p = 0.014). In multivariable analysis that adjusted for the effects of age, preoperative PSA, RP Gleason sum, seminal vesicle invasion, extracapsular extension, positive surgical margins, lymphovascular invasion, and LNI, Ki-67 was significantly associated with BCR (HR = 1.19; p = 0.019). Subgroup analysis revealed that Ki-67 is associated with BCR in patients without LNI (p = 0.004), those with RP Gleason sum 7 (p = 0.015), and those with negative surgical margins (p = 0.047). Conclusion: We confirmed Ki-67 as an independent predictor of BCR after RP. Ki-67 could be particularly informative in patients with favorable pathologic characteristics to help in the clinical decision-making regarding adjuvant therapy and optimized follow-up scheduling.
    No preview · Article · Oct 2014 · World Journal of Urology
  • Aaron Bernie · Ranjith Ramasamy · Adnan Ali · Ashutosh K Tewari
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    ABSTRACT: Introduction: We hypothesized that there is a reverse stage migration, or a shift toward operating on higher-risk prostate cancer, in patients undergoing robot-assisted laparoscopic prostatectomy (RALP). We therefore evaluated the stage of disease at the time of surgery for patients with prostate cancer at a large tertiary academic medical center. Materials and Methods: After institutional review board approval, we reviewed all patients that had undergone robotic prostatectomy. These patients were separated into three categories: An early era of 2005-2008, intermediate era of 2009-2010, and a current era of 2011-2012. Results: A total of 3451 patients underwent robotic prostatectomy from 2005 to 2012. The proportion men with clinical T1 tumors declined from 88.3% in the early era to 72.2% in the current era (P < 0.0001). Men with preoperative biopsy Gleason 6 disease decreased from the early to the current era (P < 0.0001), while men with preoperative biopsy Gleason ≥ 8 showed the opposite trend, increasing from the early to the current era (P = 0.0002). From the early to the current era, the proportion of patients with National Comprehensive Cancer Network (NCCN) low risk prostate cancer decreased, while those with NCCN intermediate and high-risk disease increased. The proportion of pathologic T3 disease increased from 15.5% in the early to 30.6% in the current era (P < 0.0001). On the other hand, the proportion of pathologic T2/+ SMS (surgical margin status) decreased from 6.6% in the early era to 3.1% in the current era (P = 0.0002). Conclusions: We have demonstrated a reverse stage migration in men undergoing robotic prostatectomy. Despite the increasing proportion of men with extra-capsular disease undergoing RALP, the surgical margin status has remained similar. This could reflect both the changing dynamics of the population opting for surgery as well as the learning curve of the surgeons.
    No preview · Article · Oct 2014 · Indian Journal of Urology
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    ABSTRACT: With more than 60% of radical prostatectomies being performed robotically, robotic-assisted laparoscopic prostatectomy (RALP) has largely replaced the open and laparoscopic approaches and has become the standard of care surgical treatment option for localized prostate cancer in the United States. Accomplishing negative surgical margins while preserving functional outcomes of sexual function and continence play a significant role in determining the success of surgical intervention, particularly since the advent of nerve-sparing (NS) robotic prostatectomy. Recent evidence suggests that NS surgery improves continence in addition to sexual function. In this review, we describe the neuroanatomical concepts and recent developments in the NS technique of RALP with a view to improving the "trifecta" outcomes.
    No preview · Article · Oct 2014 · Indian Journal of Urology
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    ABSTRACT: Background Value-based health care has been proposed as a unifying force to drive improved outcomes and cost containment. Objective To develop a standard set of multidimensional patient-centered health outcomes for tracking, comparing, and improving localized prostate cancer (PCa) treatment value. Design, setting, and participants We convened an international working group of patients, registry experts, urologists, and radiation oncologists to review existing data and practices. Outcome measurements and statistical analysis The group defined a recommended standard set representing who should be tracked, what should be measured and at what time points, and what data are necessary to make meaningful comparisons. Using a modified Delphi method over a series of teleconferences, the group reached consensus for the Standard Set. Results and limitations We recommend that the Standard Set apply to men with newly diagnosed localized PCa treated with active surveillance, surgery, radiation, or other methods. The Standard Set includes acute toxicities occurring within 6 mo of treatment as well as patient-reported outcomes tracked regularly out to 10 yr. Patient-reported domains of urinary incontinence and irritation, bowel symptoms, sexual symptoms, and hormonal symptoms are included, and the recommended measurement tool is the Expanded Prostate Cancer Index Composite Short Form. Disease control outcomes include overall, cause-specific, metastasis-free, and biochemical relapse-free survival. Baseline clinical, pathologic, and comorbidity information is included to improve the interpretability of comparisons. Conclusions We have defined a simple, easily implemented set of outcomes that we believe should be measured in all men with localized PCa as a crucial first step in improving the value of care. Patient summary Measuring, reporting, and comparing identical outcomes across treatments and treatment centers will provide patients and providers with information to make informed treatment decisions. We defined a set of outcomes that we recommend being tracked for every man being treated for localized prostate cancer.
    Full-text · Article · Sep 2014 · European Urology
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    ABSTRACT: Objectives To assess the ability of MPM to visualize, differentiate and track periprostatic nerves in an in vivo rat model, mimicking real-time imaging in humans during RP.To investigate the tissue toxicity and the reproducibility of in vivo MPM on prostatic glands in the rat after imaging and final histological correlation study.Patients and methodsIn vivo prostatic rat imaging was carried out using a custom-built bench-top MPM system generating real-time 3D histologic images, after performing survival surgery consisting of mini-laparotomies under xylazine/ketamine anesthesia exteriorizing the right prostatic lobe.The acquisition time and the depth of anesthesia were adjusted for collecting multiple images in order to track the periprostatic nerves in real-time.The rats were then monitored for 15 days before undergoing a new set of imaging under similar settings.After sacrificing the rats, their prostates were submitted for routine histology and correlation studies.ResultsIn vivo MPM images distinguished periprostatic nerves within the capsule and the prostatic glands from fresh unprocessed prostatic tissue without the use of exogenous contrast agents nor biopsy sampleReal time nerve tracking outlining the prostate was feasible and acquisition was not disturbed by motion artifactsNo serious adverse event was reported during rat monitoring; no tissue damage due to laser was seen on the imaged lobe compared to the contralateral lobe (control) allowing comparison of their corresponding histology.Conclusions For the first time, we have demonstrated that in vivo tracking of periprostatic nerves using MPM is feasible in rat models.Development of a multiphoton endoscope for intraoperative use in humans is currently in progress and must be assessed.
    No preview · Article · Aug 2014 · BJU International
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    ABSTRACT: Purpose: The aim of this study was to compare the frequency of ERG rearrangement, PTEN deletion, SPINK1 overexpression, and SPOP mutation in prostate cancer in African American and Caucasian men. Experimental design: Dominant tumor nodules from radical prostatectomy specimens of 105 African American men (AAM) were compared with 113 dominant nodules from Caucasian men (CaM). Clinical and pathologic characteristics of the two groups were similar. SPINK1 overexpression was evaluated by immunohistochemistry, ERG rearrangement and PTEN deletion by FISH, and SPOP mutation by Sanger sequencing. Results: ERG rearrangement was identified in 48 of 113 tumors (42.5%) in CaM and 29 of 105 tumors (27.6%) in AAM (P = 0.024). PTEN deletion was seen in 19 of 96 tumors (19.8%) in CaM and 7 of 101 tumors (6.9%) in AAM (P = 0.011). SPINK1 overexpression was present in 9 of 110 tumors (8.2%) in CaM and 25 of 105 tumors (23.4%) in AAM (P = 0.002). SPOP mutation was identified in 8 of 78 (10.3%) tumors in CaM and 4 of 88 (4.5%) tumors in AAM (P = 0.230). When adjusted for age, body mass index, Gleason score, and pathologic stage, ERG rearrangement and SPINK1 overexpression remain significantly different (P = 0.018 and P = 0.008, respectively), and differences in PTEN deletion and SPOP mutation approach significance (P = 0.061 and P = 0.087, respectively). Conclusions: Significant molecular differences exist between prostate cancers in AAM and CaM. SPINK1 overexpression, an alteration associated with more aggressive prostate cancers, was more frequent in AAM, whereas ERG rearrangement and PTEN deletion were less frequent in this cohort. Further investigation is warranted to determine whether these molecular differences explain some of the disparity in incidence and mortality between these two ethnic groups.
    Preview · Article · Jul 2014 · Clinical Cancer Research
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    ABSTRACT: We characterize the diagnostic performance of a multiphoton GRIN endoscope using human prostate samples obtained from radical prostatectomy surgery. Ex vivo images of benign and tumor areas and images of peri-prostatic tissue are shown.
    No preview · Conference Paper · Jun 2014
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    ABSTRACT: To analyze the learning curve for cancer control from an initial 250 cases (Group I) and subsequent 250 cases (Group II) of robotic-assisted laparoscopic radical prostatectomy (RALP) performed by a single surgeon. Five hundred consecutive patients with clinically localized prostate cancer received RALP and were evaluated. Surgical parameters and perioperative complications were compared between the groups. Positive surgical margin (PSM) and biochemical recurrence (BCR) were assessed as cancer control outcomes. Patients in Group II had significantly more advanced prostate cancer than those in Group I (22.2% vs 14.2%, respectively, with Gleason score 8-10, 0P= 0.033; 12.8% vs 5.6%, respectively, with clinical stage T3, P= 0.017). The incidence of PSM in pT3 was decreased significantly from 49% in Group I to 32.6% in Group II. A meaningful trend was noted for a decreasing PSM rate with each consecutive group of 50 cases, including pT3 and high-risk patients. Neurovascular bundle (NVB) preservation was significantly influenced by the PSM in high-risk patients (84.1% in the preservation group vs 43.9% in the nonpreservation group). The 3-year, 5-year, and 7-year BCR-free survival rates were 79.2%, 75.3%, and 70.2%, respectively. In conclusion, the incidence of PSM in pT3 was decreased significantly after 250 cases. There was a trend in the surgical learning curve for decreasing PSM with each group of 50 cases. NVB preservation during RALP for the high-risk group is not suggested due to increasing PSM.
    Full-text · Article · May 2014 · Asian Journal of Andrology

Publication Stats

9k Citations
1,391.20 Total Impact Points

Institutions

  • 2015
    • National Yang Ming University
      T’ai-pei, Taipei, Taiwan
  • 2014-2015
    • Mount Sinai Hospital
      New York, New York, United States
    • Sinai Hospital
      New York, New York, United States
  • 2013-2015
    • Icahn School of Medicine at Mount Sinai
      • Department of Urology
      Borough of Manhattan, New York, United States
  • 2007-2014
    • Cornell University
      Итак, New York, United States
  • 2006-2014
    • Weill Cornell Medical College
      • • Department of Pathology and Laboratory Medicine
      • • Department of Urology
      New York, New York, United States
  • 2005-2014
    • New York Presbyterian Hospital
      • Department of Urology
      New York, New York, United States
    • Virginia Mason Medical Center
      Seattle, Washington, United States
    • University of Innsbruck
      • Department of Statistics
      Innsbruck, Tyrol, Austria
    • University of Michigan
      Ann Arbor, Michigan, United States
  • 2011
    • Stanford University
      Stanford, California, United States
  • 2010
    • Gracie Square Hospital, New York, NY
      New York, New York, United States
  • 2008
    • Universidad Autónoma de Madrid
      Madrid, Madrid, Spain
  • 2004-2005
    • Michigan Institute of Urology
      Detroit, Michigan, United States
  • 2002-2005
    • Henry Ford Health System
      Detroit, Michigan, United States
    • Detroit Medical Center
      • Division of Urology
      Detroit, Michigan, United States
    • Pierre and Marie Curie University - Paris 6
      Lutetia Parisorum, Île-de-France, France
  • 1999-2005
    • Henry Ford Hospital
      • Surgery
      Detroit, Michigan, United States
  • 2003
    • Case Western Reserve University School of Medicine
      • Department of Urology
      Cleveland, Ohio, United States
  • 1998
    • San Francisco VA Medical Center
      San Francisco, California, United States
  • 1995-1998
    • University of Florida
      • Department of Urology
      Gainesville, Florida, United States
  • 1995-1996
    • University of California, San Francisco
      • • Department of Urology
      • • Veterans Affairs Medical Center
      San Francisco, California, United States