Alon Z Weizer

University of Michigan, Ann Arbor, Michigan, United States

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Publications (166)521.01 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Inverted urothelial papilloma (IUP) is an uncommon neoplasm of the urinary bladder with distinct morphological features. Studies regarding the role of human papillomavirus (HPV) in the etiology of IUP have provided conflicting evidence of HPV infection. Additionally, little is known regarding the molecular alterations present in IUP or other urothelial neoplasms which might demonstrate inverted growth pattern like low-grade or high-grade urothelial carcinoma. Here, we evaluated for the presence of common driving somatic mutations and HPV within a cohort of inverted urothelial papillomas, (n = 7) noninvasive low-grade papillary urothelial carcinomas with inverted growth pattern (n = 5,) and noninvasive high-grade papillary urothelial carcinomas with inverted growth pattern (n = 8). HPV was not detected in any case of inverted urothelial papilloma or inverted urothelial carcinoma by either ISH or by PCR. Next generation sequencing identified recurrent mutations in HRAS (Q61R) in 3 of 5 inverted urothelial papillomas, described for the first time in this neoplasm. Additional mutations of Ras pathway members were detected including HRAS, KRAS, and BRAF. The presence of Ras pathway member mutations at a relatively high rate suggests this pathway may contribute to pathogenesis of inverted urothelial neoplasms. Additionally, we did not find any evidence supporting a role for HPV in the etiology of inverted urothelial papilloma.
    Human pathology 09/2014; · 3.03 Impact Factor
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    ABSTRACT: Prostate capsule sparing and nerve sparing cystectomies are alternative procedures for bladder cancer that may reduce morbidity while achieving cancer control. However, the comparative effectiveness of these approaches has not been established. We sought to evaluate the functional and oncologic outcomes of patients undergoing these two procedures.
    The Journal of urology. 07/2014;
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    ABSTRACT: Robot-assisted radical cystectomy (RARC) is an emerging operative alternative to open surgery for the management of invasive bladder cancer. Studies from single institutions provide limited data due to the small number of patients. In order to better understand the related outcomes, a world-wide consortium was established in 2006 of patients undergoing RARC, called the International Robotic Cystectomy Consortium (IRCC). Thus far, the IRCC has reported its findings on various areas of operative interest and continues to expand its capacity to include other operative modalities and transform it into the International Radical Cystectomy Consortium. This article summarizes the findings of the IRCC and highlights the future direction of the consortium.
    Indian journal of urology : IJU : journal of the Urological Society of India. 07/2014; 30(3):314-7.
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    ABSTRACT: To determine the relationship between prostate gland and tumor volume in men undergoing radical prostatectomy (RP) for prostate cancer. We hypothesized that larger tumors within smaller prostate glands are associated with more aggressive disease characteristics.
    Urology 06/2014; · 2.42 Impact Factor
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    ABSTRACT: Robot-assisted retroperitoneoscopic partial nephrectomy (RARPN) may be used for posterior renal masses or with prior abdominal surgery; however, there is relatively less familiarity with RARPN.
    European urology. 05/2014;
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    ABSTRACT: Preservation of renal function is the major benefit of partial over radical nephrectomy. We evaluated patients undergoing minimally invasive partial nephrectomy (MIPN) to better understand factors predicting long-term renal function.
    Urologic oncology. 05/2014;
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    ABSTRACT: To evaluate health-related quality of life (HRQL) using validated bladder-specific Bladder Cancer Index (BCI) and European Organization for Research and Treatment of Cancer Body Image scale (BIS) between open radical cystectomy (ORC) and robot-assisted radical cystectomy (RARC). This was a retrospective case series of all patients who underwent radical cystectomy. Patients were grouped based on surgical approach (open vs robot assisted) and diversion technique (extracorporeal vs intracorporeal). Patients completed BCI and BIS preoperatively and at standardized postoperative intervals (at least 2). The primary exposure variable was surgical approach. The primary outcome measure was difference in interval and baseline BCI and BIS scores in each group. The Fisher exact, Wilcoxon rank-sum, and Kruskal-Wallis tests were used for comparisons. Eighty-two and 100 patients underwent RARC and ORC, respectively. Compared with RARC, more patients undergoing ORC had an American Society of Anesthesiology score ≥3 (66% vs 45.1% RARC; P = .007) and shorter median operative time (350 vs 380 minutes; P = .009). Baseline urinary, bowel, sexual function, and body image were not different between both the groups (P = 1.0). Longitudinal postoperative analysis revealed better sexual function in ORC group (P = .047), with no significant differences between both the groups in the other 3 domains (P = .11, .58, and .93). Comparisons regarding diversion techniques showed similar findings in baseline and postoperative HRQL data, with no significant differences in the HRQL and body image domains. RARC has comparable HRQL outcomes to ORC using validated BCI and BIS. The diversion technique used does not seem to affect patients' quality of life.
    Urology 04/2014; · 2.42 Impact Factor
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    ABSTRACT: To present the benefits and utility of tumor enucleation as an alternative technique to sharp excision during minimally invasive partial nephrectomy (MIPN). We retrospectively compared enucleation and sharp excision during MIPN, with the aim of determining benefits and limitations of enucleation in this setting. Among 602 patients undergoing MIPN at our institution, 86 and 516 underwent enucleation and sharp excision, respectively, as determined by the surgeon. The nephrometry score was greater in the enucleation vs sharp excision group (mean, 6.7 vs 6.3), but all other preoperative parameters were similar. The mean ischemia and operative times were 4 and 32 minutes shorter in the enucleation group, respectively, likely owing to less frequent entry into renal sinus (21% vs 41%) and need for tumor bed suturing (41% vs 62%), compared with those in the sharp excision group. There was no association with blood loss, positive margins, urine leak, blood transfusion, major complications, renal function, recurrence, or survival. Enucleation appears to provide the benefits of reduced surgical entry into the renal sinus, less need for tumor bed suturing, and shorter operative time, without any impact on functional or oncologic outcomes. Given favorable preoperative radiography and intraoperative findings, enucleation is a useful technique for patients undergoing MIPN.
    Urology 04/2014; · 2.42 Impact Factor
  • European Urology Supplements 04/2014; 13(1):e17–e17a. · 3.37 Impact Factor
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    ABSTRACT: Objectives The purpose of the RAZOR study is to compare open versus robotic radical cystectomy, pelvic lymph node dissection and urinary diversion regarding oncologic outcomes, complications and quality of life measures with a primary endpoint of 2-year progression free survival. Patients and MethodsRAZOR is a multi-institutional, randomized, non-inferior, phase 3 trial that will enroll at least 320 patients with T1-T4, N0-1, M0 bladder cancer with approximately 160 patients in both robotic and open arms at a total of 15 participating institutions.Data will be collected prospectively at each institution regarding cancer outcomes, complications from surgery and quality of life measures and then submitted to trial data management services, Cancer Research and Biostatistics (CRAB) for final analyses. Results306 patients have been randomized to date and accrual to the RAZOR trial is expected to conclude in 2014.In this study, we report RAZOR trial experimental design, objectives, data safety and monitoring and accrual update. Conclusions The RAZOR trial is a landmark study in urological oncology, randomizing T1-T4, N0-N1, M0 bladder cancer patients to open versus robotic radical cystectomy, pelvic lymph node dissection and urinary diversion.RAZOR is a multi-institutional, non-inferiority trial evaluating cancer outcomes, surgical complications and quality of life measures of open versus robotic cystectomy with a primary endpoint of 2-year progression free survival.Full data from the RAZOR trial are not expected until 2016—2017.
    BJU International 02/2014; · 3.05 Impact Factor
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    ABSTRACT: Readmissions after radical cystectomy are common, burdensome, and poorly understood. For these reasons, the authors conducted a population-based study that focused on the causes of and time to readmission after radical cystectomy. Using Surveillance, Epidemiology, and End Results-Medicare data, at total of 1782 patients who underwent radical cystectomy from 2003 through 2009 were identified. A piecewise exponential model was used to examine reasons for readmission as well as patient and clinical factors associated with the timing of readmission. One in 4 patients (25.5%) were readmitted within 30 days of discharge after radical cystectomy. Compared with patients without readmission, those readmitted were similar with regard to age, sex, and race. Readmitted patients had more complications (33.8% vs 13.9%; P < .001) and were more likely to have been discharged to skilled nursing facilities from their index admission (P < .001). The average time to readmission and subsequent length of stay were 11.5 days and 6.7 days, respectively. The majority of readmissions (67.4%) occurred within 2 weeks of discharge, 66.8% had emergency department charges, and 25.9% involved intensive care unit use. Although the spectrum of reasons for readmission varied over the 4 weeks after discharge, the most common included infection (51.4%), failure to thrive (36.3%), and urinary (33.2%) and gastrointestinal (23.1%) etiologies; 95.8% of patients had ≥ 1 of these diagnosis groups present at the time of readmission. Readmissions after radical cystectomy are common and time-dependent. Interventions to prevent and reduce the readmission burden after cystectomy likely need to focus on the first 2 weeks after discharge, take into consideration the spectrum of reasons for readmission, and target high-risk individuals. Cancer 2014. © 2014 American Cancer Society.
    Cancer 01/2014; · 5.20 Impact Factor
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    ABSTRACT: Objective: To report the long-term oncologic outcomes and survival estimates associated with MIPN, and to determine factors associated with those outcomes and survival estimates. Methods: A single-institution, retrospective review was performed on all patients undergoing MIPN for renal cell carcinoma between 1998 and 2011 with minimum 1-year follow-up. Bivariate and multivariate analyses were performed to assess associations between demographic, perioperative, and tumor factors with recurrence and survival. Survival was estimated utilizing the Kaplan-Meier method. Results: Of 417 patients undergoing MIPN, median overall and oncologic follow-up were 3.3 and 2.9 years, respectively. The mean patient age was 63 years (SD: +/- 13.4). The mean tumor size was 2.9 cm (SD: +/- 1.48). Only 6.7% of patients had a pathologic stage T2 or greater. There was only 1 cancer-related death. Estimates for overall survival at 2, 5 years and 10 years were 95.6%, 89.1% and 70.7%, respectively. Estimates for recurrence-free survival (any recurrence) at 2, 5 years and 10 years were 98.2%, 93.5% and 88.3%, respectively. On multivariate analysis, only tumor stage was associated with recurrence, and only patient age and ASA score were associated with overall survival. Technical aspects of the procedure, such as positive margins or use of enucleation, did not influence recurrence or survival. Conclusions: Cancer recurrence after MIPN, in a cohort of mostly pT1 tumors, is rare. Recurrence and overall survival are associated with non-modifiable factors rather than technical ones.
    Journal of endourology / Endourological Society 01/2014; · 1.75 Impact Factor
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    ABSTRACT: Primary clear-cell adenocarcinoma of the urethra, a rare tumor that histomorphologically resembles clear-cell carcinoma of the female genital tract, occurs predominantly in women and is associated with a relatively poor prognosis. The histogenesis of this rare urethral neoplasm has not been completely resolved, but it is thought to arise from either müllerian rests or metaplastic urothelium. Herein, we present comprehensive surgical pathological and cytopathological findings from a patient with primary urethral clear-cell adenocarcinoma and describe next-generation sequencing results for this patient's unique tumor-the first such reported characterization of molecular aberrations in urethral clear-cell adenocarcinoma at the transcriptomic and genomic levels. Transcriptome analysis revealed novel gene fusion candidates, including ANKRD28-FNDC3B. Whole-exome analysis demonstrated focal copy number loss at the SMAD4 and ARID2 loci and 38 somatic mutations, including a truncating mutation in ATM and a novel nonsynonymous mutation in ALK.
    American Journal Of Pathology 01/2014; · 4.60 Impact Factor
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    ABSTRACT: Objective Preservation of renal function is the major benefit of partial over radical nephrectomy. We evaluated patients undergoing minimally invasive partial nephrectomy (MIPN) to better understand factors predicting long-term renal function. Methods We identified 358 patients who underwent MIPN for confirmed renal cell carcinoma between 1998 and 2011 with a serum creatinine level at least 1 year postoperatively. Exposure variables included demographic, clinical, and perioperative information. The primary outcome was clinically significant progression of chronic kidney disease (CKD) class, defined as estimated glomerular filtration rate (eGFR) decreasing from >60 to<60, from 30 to 60 to <30, or from 15 to 30 to<15. Bivariate and multivariate analyses were performed. Results Median follow-up was 39 months. Only 7 patients had a solitary kidney. A total of 47 patients (13%) had CKD class progression. The estimates for remaining free of CKD class progression at 5, 7, and 10 years were 86.98%, 75.45%, and 53.54%, respectively. On multivariate analysis, lower preoperative eGFR (odds ratio [OR] = 0.97, 95% CI: 0.96–0.98), larger tumor size (OR = 1.22, 95% CI: 1.01–1.48), and longer ischemia time (OR = 1.03, 95% CI: 1.01–1.05) were associated with CKD class progression. Conclusions Clinically significant progression of CKD occurs in a minority of patients 5 years after MIPN, but in almost one-half, it occurs 10 years after surgery. Lower preoperative eGFR and larger tumor size are associated with greater incidence of CKD progression. Longer ischemia time, even when most patients had 2 kidneys and when controlling for other factors, nonetheless increased the risk of CKD progression, although this may be a marker of other unmeasured variables.
    Urologic Oncology: Seminars and Original Investigations. 01/2014;
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    ABSTRACT: Objective To present the benefits and utility of tumor enucleation as an alternative technique to sharp excision during minimally invasive partial nephrectomy (MIPN). Methods We retrospectively compared enucleation and sharp excision during MIPN, with the aim of determining benefits and limitations of enucleation in this setting. Results Among 602 patients undergoing MIPN at our institution, 86 and 516 underwent enucleation and sharp excision, respectively, as determined by the surgeon. The nephrometry score was greater in the enucleation vs sharp excision group (mean, 6.7 vs 6.3), but all other preoperative parameters were similar. The mean ischemia and operative times were 4 and 32 minutes shorter in the enucleation group, respectively, likely owing to less frequent entry into renal sinus (21% vs 41%) and need for tumor bed suturing (41% vs 62%), compared with those in the sharp excision group. There was no association with blood loss, positive margins, urine leak, blood transfusion, major complications, renal function, recurrence, or survival. Conclusion Enucleation appears to provide the benefits of reduced surgical entry into the renal sinus, less need for tumor bed suturing, and shorter operative time, without any impact on functional or oncologic outcomes. Given favorable preoperative radiography and intraoperative findings, enucleation is a useful technique for patients undergoing MIPN.
    Urology 01/2014; · 2.42 Impact Factor
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    ABSTRACT: Objective To determine the relationship between prostate gland and tumor volume in men undergoing radical prostatectomy (RP) for prostate cancer. We hypothesized that larger tumors within smaller prostate glands are associated with more aggressive disease characteristics. Methods Records of patients undergoing RP from 2000-2008 at a single institution were reviewed retrospectively. The dominant nodule was considered to be the largest focus of cancer within the prostate, and the dominant nodule-to-prostate volume ratio (DNVR) was calculated according to the ratio of the dominant nodule volume to the gland weight. Cox regression was performed to assess the relationship between DNVR and both pathologic outcomes (Cancer of the Prostate Risk Assessment post-Surgical score) and biochemical recurrence (BCR). Results At a median follow-up of 3.7 years, 174 patients (7.2%) suffered BCR. There was no linear correlation between tumor volume and gland size (R = −0.09). DNVR above the median (≥0.033 cc/gm) was closely associated with high clinicopathologic risk as measured by Cancer of the Prostate Risk Assessment post-Surgical score (hazard ratio, 35.53; 95% confidence interval, 14.42-87.55 for high- vs low-risk groups). In the univariable analysis, both tumor diameter and DNVR were associated with increased risk of BCR. However, in the multivariable model, only tumor diameter remained a significant predictor of BCR (hazard ratio, 2.02; 95% confidence interval, 1.04-3.91). Conclusion Increased DNVR appears to be a characteristic of aggressive prostate tumors, although it did not predict BCR in the present study. However, these data support the association between tumor diameter and BCR after RP for prostate cancer independent of other key clinicopathologic features.
    Urology 01/2014; · 2.42 Impact Factor
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    ABSTRACT: Papillary renal cell carcinoma (P-RCC) is the second most common type of malignant renal epithelial tumor, and can be subclassified into type 1, which demonstrates simple cuboidal low-grade epithelium, and type 2, which demonstrates pseudostratified high grade epithelium with abundant eosinophilic cytoplasm. Despite this clinically useful subclassification, P-RCCs exhibit considerable histomorphologic diversity, with many cases having features differing from classically described type 1 and type 2 tumors. To our knowledge, there has been no recent study which has methodically evaluated the histomorphologic features of a series of P-RCCs. To address this, we evaluated a cohort of P-RCCs diagnosed between 1997 and 2004 with long term clinical follow-up data (n = 56). Histomorphologic features previously described in the spectrum of type 1 and type 2 P-RCCs were recorded for each tumor, including nuclear grade, complete tumor capsule, and cytoplasmic eosinophilia, as well as several other features. The current TNM staging (AJCC 7th edition) was assigned to all cases. Histomorphologic features were diverse, demonstrating classic type 1 P-RCC and classic type 2 P-RCC morphology, and several tumors with non-classical features. Four patients in this cohort had distant metastasis. The primary tumor was equally divided between type 1 (2 cases) and type 2 (2 cases) morphology in the cases with metastasis. All P-RCC cases with metastases demonstrated presence of high nuclear grade and high tumor stage in the primary tumor. Cluster analysis using staging parameters and histomorphologic features divided tumors into two primary clusters. All primary tumors associated with metastasis were in the same cluster.
    Human pathology 01/2014; · 3.03 Impact Factor
  • Source
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    ABSTRACT: Objective To evaluate health-related quality of life (HRQL) using validated bladder-specific Bladder Cancer Index (BCI) and European Organization for Research and Treatment of Cancer Body Image scale (BIS) between open radical cystectomy (ORC) and robot-assisted radical cystectomy (RARC). Methods This was a retrospective case series of all patients who underwent radical cystectomy. Patients were grouped based on surgical approach (open vs robot assisted) and diversion technique (extracorporeal vs intracorporeal). Patients completed BCI and BIS preoperatively and at standardized postoperative intervals (at least 2). The primary exposure variable was surgical approach. The primary outcome measure was difference in interval and baseline BCI and BIS scores in each group. The Fisher exact, Wilcoxon rank-sum, and Kruskal-Wallis tests were used for comparisons. Results Eighty-two and 100 patients underwent RARC and ORC, respectively. Compared with RARC, more patients undergoing ORC had an American Society of Anesthesiology score ≥3 (66% vs 45.1% RARC; P = .007) and shorter median operative time (350 vs 380 minutes; P = .009). Baseline urinary, bowel, sexual function, and body image were not different between both the groups (P = 1.0). Longitudinal postoperative analysis revealed better sexual function in ORC group (P = .047), with no significant differences between both the groups in the other 3 domains (P = .11, .58, and .93). Comparisons regarding diversion techniques showed similar findings in baseline and postoperative HRQL data, with no significant differences in the HRQL and body image domains. Conclusion RARC has comparable HRQL outcomes to ORC using validated BCI and BIS. The diversion technique used does not seem to affect patients' quality of life.
    Urology 01/2014; · 2.42 Impact Factor
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    ABSTRACT: Purpose To assess the relationship between healthcare system performance on nationally endorsed prostate cancer quality of care measures and prostate cancer treatment outcomes. Methods This is a retrospective cohort study including 48,050 men from Surveillance Epidemiology and End Results – Medicare linked data who were diagnosed with localized prostate cancer between 2004 and 2009 and followed through 2010. Based on a composite quality measure, we categorized the healthcare systems in which these men were treated into 1-star (bottom 20%), 2-star (middle 60%), and 3-star (top 20%) systems. We then examined the association of healthcare system-level quality of care with outcomes using multivariable logistic and Cox regression. Results Patients who underwent prostatectomy in 3-star versus 1-star healthcare systems had a lower risk of perioperative complications (odds ratio 0.80, 95% confidence interval [CI] 0.64-1.00). However, these patients were more likely to undergo a procedure addressing treatment-related morbidity (e.g., 11.3% vs. 7.8% treated for sexual morbidity, p=0.043). Among patients undergoing radiotherapy, star-ranking was not associated with treatment-related morbidity. Among all patients, star-ranking was not significantly associated with all-cause mortality (Hazard Ratio [HR] 0.99, 95% CI 0.84-1.15) or secondary cancer therapy (HR 1.04, 95% CI 0.91-1.20). Conclusion We found no consistent associations between healthcare system quality and outcomes, which questions how meaningful these measures ultimately are for patients. Thus, future studies should focus on the development of more discriminative quality measures.
    The Journal of urology 01/2014; · 3.75 Impact Factor
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    ABSTRACT: Upper tract urothelial carcinoma (UTUC) is a clinically heterogeneous disease that lacks high-quality trials that provide definitive prognostic markers. Insulin-like growth factor messenger RNA binding protein 3 (IMP3) has been associated with outcomes in urothelial carcinoma of the bladder but was not yet studied in UTUC. To evaluate the association of the oncofetal protein IMP3 with oncologic outcomes in patients with UTUC treated with radical nephroureterectomy (RNU). We investigated the expression of IMP3 and its association with clinical outcomes using tissue microarrays constructed from 622 patients treated with RNU at seven international institutions between 1991 and 2008. All patients were diagnosed with UTUC and underwent RNU. Uni- and multivariable Cox regression analyses evaluated the association of IMP3 protein expression with disease recurrence, cancer-specific mortality, and all-cause mortality. IMP3 was expressed in 12.2% of patients with UTUC (n=76). The expression was tumor specific and correlated with higher stages/grades. Within a median follow-up of 27 mo (interquartile range [IQR]: 12-53), 191 patients (25.4%) experienced disease recurrence, and 165 (21.9%) died of the disease. Patients with IMP3 demonstrated significantly worse recurrence-free survival (27.4% vs 75.1%; p<0.01), cancer-specific survival (34.5% vs 78.9%; p<0.01), and overall survival (15.6% vs 64.8%; p<0.01) at 5 yr compared with those without IMP3. In multivariable Cox regression analyses, which adjusted for the effects of standard clinicopathologic features, IMP3expression was independently associated with disease recurrence (hazard ratio [HR]: 1.87; p<0.01), cancer-specific mortality (HR: 2.15; p<0.01), and all-cause mortality (HR: 2.07; p<0.01). Major limitations include the retrospective design and relatively short follow-up time. IMP3 expression is independently associated with disease recurrence, cancer-specific mortality, and all-cause mortality in UTUC. IMP3 may help improve risk stratification and prognostication of UTUC patients treated with RNU.
    European Urology 12/2013; · 10.48 Impact Factor

Publication Stats

2k Citations
521.01 Total Impact Points

Institutions

  • 1970–2014
    • University of Michigan
      • Department of Urology
      Ann Arbor, Michigan, United States
  • 2013
    • Roswell Park Cancer Institute
      • Department of Urology
      Buffalo, New York, United States
  • 2012–2013
    • Weill Cornell Medical College
      • Department of Urology
      New York City, New York, United States
  • 2008–2013
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
    • University of Texas at Dallas
      Richardson, Texas, United States
    • Keio University
      Edo, Tōkyō, Japan
    • Medical University of Vienna
      • Department of Urology
      Wien, Vienna, Austria
  • 2011
    • Kitasato University
      • Department of Urology
      Edo, Tōkyō, Japan
  • 2009–2011
    • New York Presbyterian Hospital
      • Department of Urology
      New York City, New York, United States
    • University of Texas Southwestern Medical Center
      • Department of Urology
      Dallas, TX, United States
    • Howard Hughes Medical Institute
      Ashburn, Virginia, United States
    • Università Vita-Salute San Raffaele
      Milano, Lombardy, Italy
  • 2002–2003
    • Duke University Medical Center
      • Division of Urology
      Durham, NC, United States